BSc Honours Projects 2014 CHEMISTRY, BIOCHEMISTRY & MOLECULAR BIOLOGY and MICROBIOLOGY & PARASITOLOGY School of Chemistry & Molecular Biosciences Faculty of Science
BSc Honours Projects 2014
CHEMISTRY, BIOCHEMISTRY & MOLECULAR BIOLOGY andMICROBIOLOGY & PARASITOLOGY
School of Chemistry & Molecular BiosciencesFaculty of Science
Chemistry & Molecular Biosciences Honours Projects 2014
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CONTENTS
THE HONOURS PROGRAM Page No.
HONOURS IN CHEMISTRY, BIOCHEMISTRY & MOLECULAR BIOLOGY, MICROBIOLOGY & PARASITOLOGY 2014
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SCMB ACADEMIC STAFF SCMB Contributors School Location Page No.
Prof Stephen Barker Molecular Biosciences Building 8
Prof Paul Bernhardt Chemistry Building 9
Dr Joanne Blanchfield Chemistry Building 10
Dr Mikael Boden Molecular Biosciences Building 11
Prof Melissa Brown Chemistry Building 12
Prof Paul Burn Chemistry Building, COPE 13
A/Prof Bernie Carroll Molecular Biosciences Building 14
Dr Jack Clegg Chemistry Building 15
Prof James De Voss Chemistry Building 16
A/Prof Vito Ferro Chemistry Building 17
Dr James Fraser Molecular Biosciences Building 18
Prof Lawrence Gahan Chemistry Building 19
Prof Mary Garson Chemistry Building 20
Prof Ian Gentle Chemistry Building 21
Prof Elizabeth Gillam Molecular Biosciences Building 22
A/Prof Lisbeth Grondahl Chemistry Building 23
A/Prof Luke Guddat Molecular Biosciences Building 24
Prof Roy Hall Molecular Biosciences Building 25
Prof Phil Hugenholtz & Dr Gene Tyson Molecular Biosciences Building, ACE 26
Dr Ulrike Kappler Molecular Biosciences Building 27
A/Prof Stuart Kellie Molecular Biosciences Building 28
Prof Alexander Khromykh Molecular Biosciences Building 29
Prof Bostjan Kobe Molecular Biosciences Building 30
Dr Gwen Lawrie Chemistry Building 31
Dr Shih‐Chun (Lawrence) Lo Chemistry Building, COPE 32
Prof Alan Mark Molecular Biosciences Building 33
A/Prof Ross McGeary Chemistry Building 34
Dr Evan Moore Chemistry Building 35
Prof Peter O’Donoghue Molecular Biosciences Building 36
A/Prof Mark Riley Chemistry Building 37
A/Prof Joe Rothnagel Molecular Biosciences Building 38
Dr Susan Rowland Molecular Biosciences Building 39
Prof Mark Schembri Molecular Biosciences Building 40
A/Prof Gary Schenk Chemistry Building 41
Prof Ross Smith Molecular Biosciences Building 42
Dr Kate Stacey Molecular Biosciences Building 43
Prof Istvan Toth Chemistry Building 44
Prof Mark Walker Molecular Biosciences Building 45
Dr Jack Wang Molecular Biosciences Building 46
A/Prof Leigh Ward Molecular Biosciences Building 47
Dr Nick West Molecular Biosciences Building 48
A/Prof Craig Williams Chemistry Building 49
Dr Simon Worrall Molecular Biosciences Building 50
Prof Paul Young Molecular Biosciences Building 51
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SCMB ACADEMIC STAFF WITH JOINT APPOINTMENTS Joint Contributors Organisation/Business Unit Page No.
Prof Debra Bernhardt Australian Institute for Bioengineering and Nanotechnology (AIBN)
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Dr Graham Leggatt University of Queensland Diamantina Institute (UQDI)
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Prof Michael Monteiro Australian Institute for Bioengineering and Nanotechnology (AIBN)
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Prof Matt Trau Australian Institute for Bioengineering and Nanotechnology (AIBN)
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SCMB RESEARCH FELLOWS Research Fellow Contributors School Location Page No.
Dr Elizabeth Krenske Molecular Biosciences Building 56
Dr Megan O’Mara Molecular Biosciences Building 56
Dr Benjamin Schulz Molecular Biosciences Building 57
Dr Annette Shewan Molecular Biosciences Building 57
Dr Pavla Simerska Chemistry Building 58
Dr Mariusz Skwarczynski Chemistry Building 58
Dr Makrina Totsika Molecular Biosciences Building 59
Dr George Vamvounis Chemistry Building, COPE 59
SCMB AFFILIATE STAFF Affiliate Contributors Organisation/Business Unit
Prof Paul Alewood Institute for Molecular Bioscience (IMB) 60
Prof Rob Capon Institute for Molecular Bioscience (IMB) 60
A/Prof Nick Davis‐Poynter Sir Albert Sakzewski Virus Research Centre/Clinical Medical Virology Centre (SASVRC/CMVC)
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Dr Annette Dexter Australian Institute for Bioengineering and Nanotechnology (AIBN)
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A/Prof Ralf Dietzgen Queensland Alliance for Agriculture and Food Innovation (QAAFI)
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Prof David Fairlie Institute for Molecular Bioscience (IMB) 62
Dr Mary Fletcher Queensland Alliance for Agriculture and Food Innovation (QAAFI)
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Prof Robert G Gilbert Centre for Nutrition and Food Sciences (CNAFS) 63
Prof Glenn King Institute for Molecular Bioscience (IMB) 64
Dr Kirsten Spann Sir Albert Sakzewski Virus Research Centre/Clinical Medical Virology Centre (SASVRC/CMVC)
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A/Prof Rick Sturm Institute for Molecular Bioscience (IMB) 65
Dr Matt Sweet Institute for Molecular Bioscience (IMB) 65
A/Prof Rohan Teasdale Institute for Molecular Bioscience (IMB) 66
Prof Brandon Wainwright Institute for Molecular Bioscience (IMB) 66
Prof Andrew Whittaker Australian Institute for Bioengineering and Nanotechnology (AIBN)
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AFFILIATED INSTITUTIONS Organisation/Business Unit Page No.
Advanced Water Management Centre (AWMC) 68
Australian Institute for Bioengineering & Nanotechnology (AIBN)
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Centre for Advanced Imaging (CAI) 68
Institute for Molecular Bioscience (IMB) 68
University of Queensland Centre for Clinical Research (UQCCR)
68
University of Queensland Diamantina Institute 68
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(UQDI)
EXTERNAL INSTITUTIONS INCLUDING SCMB ADJUNCT ACADEMIC STAFF External Contributors Organisation/Business Unit Page No.
Prof John Manners CSIRO 69
Prof Mark Morrison CSIRO 69
Prof Jeff Gorman Queensland Institute of Medical Research (QIMR) 69
Dr Lutz Krause Queensland Institute of Medical Research (QIMR) 69‐70
A/Prof Ian M Mackay Sir Albert Sakzewski Virus Research Centre (SASVRC)
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INDUSTRY PROJECTSIndustry Contributors Organisation/Business Unit Page No.
Honours in Industry 71
Prof James De Voss & Dr Joanne Blanchfield Integria Healthcare 73
Prof Ross Barnard Cook Medical 74
Sirromet Wines 74
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HONOURS IN CHEMISTRY, BIOCHEMISTRY & MOLECULAR BIOLOGY,
MICROBIOLOGY & PARASITOLOGY 2014
The School of Chemistry & Molecular Biosciences (SCMB) offers the Bachelor of Science with Honours, BSc(Hons). It is undertaken on a full‐time basis. The Program can be commenced in either first or second semester.
The Importance of an Honours year The BSc(Hons) Program provides training well beyond that provided by the basic BSc degree, particularly in the area of research methods and in problem solving. For those students seeking employment after their degree, the extra training of Honours equips them for a wider range of positions, in industry, government laboratories and elsewhere, than does the basic BSc degree. Honours graduates generally have a greater involvement in research and development; responsibility levels are higher and there are better financial rewards. Honours is also the key prerequisite for enrolment in a higher degree. An Honours year graded at Class I allows for direct enrolment into a PhD program. Often a Class IIA performance allows admission also. Entry Requirements The Honours program can be entered from the BSc degree from this or another university. For students from the University of Queensland, normally 8 units (#8) of relevant third level courses should have been completed, at a Grade Point Average of 4.5 or above. In some cases courses from other relevant disciplines may be included in the #8. The School of Chemistry and Molecular Biosciences has some discretion in the application of the entry rules, and may, on the recommendation of the Honours Director, allow entry from students who fall slightly below this cut‐off. Students with a good academic record may also be accepted with a BSc qualification from another university. An original or certified copy of your final academic transcript must be submitted with your application form. International students must submit an application form through the International Office. Visit their web site on www.uq.edu.au/international/ or contact any IDP Education Australia office or Australian Diplomatic Mission in your capital city. Enrolment Procedures, Fees and Charges Apply to enrol in the Honours program by completing the form available from the school reception office 68‐302 (Chemistry Building) and submitting to the office of the Honours Administrative Assistant, Louise Nimwegen 68‐316. Forms can also be downloaded from the School website www.scmb.uq.edu.au. Successful applicants will be sent an offer letter after all results are known. On acceptance their enrolment in the program will be activated by the School. Honours students must enrol themselves via mySI‐net in the relevant courses for each semester. Any queries related to enrolment may be directed to Louise Nimwegen ([email protected]) or Tammie Fair ([email protected]). Full time domestic Honours students study as undergraduate Commonwealth supported students and are required to pay a Student Contribution Amount in both semesters of their Honours program. It is the student’s responsibility to ensure they educate themselves on their individual requirement with regard to their Student Contribution Amount. As a first step you may consult the UQ Fees and Costs website www.uq.edu.au/study/index.html?page=947 (further details can be obtained from the Student Centre, Level 1 JD Story Building (61). International students please see International Office website for current fees: www.uq.edu.au/international/).
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Financial Support Up to six hours per week of teaching duties may be available. All Honours students (depending on past experience) are eligible to seek employment as part‐time tutors for laboratory classes within the School of Chemistry & Molecular Biosciences. Please indicate your interest to undertake tutoring on the Honours application form. Commencement Date The commencement dates for Honours students will be Monday 10 February or, mid‐year, Monday 28 July 2014. A number of introductory programs for Honours students are run early in the semester. These comprise:
School Safety Induction, where School procedures are explained, particularly safety and waste disposal methods (mandatory)
Tutor Training
A library course, where use of electronic databases are described. Training is provided for referencing software (eg. EndNote).
Research Projects Students are invited to discuss the projects listed in this booklet with the staff members concerned and to submit the application form to the School of Chemistry & Molecular Biosciences as set out above. The Honours Program Directors will make recommendations on assignment of supervisors, taking into account:
the student’s preferences
the academic background of the student
the total number of students supervised by each staff member
resource implications
planned extended absences of the staff member from the School
other factors that may affect the staff member’s ability to supervise effectively a particular student’s research project.
For students starting in semester 1, it is highly recommended to submit your application before the end of semester 2 the previous year (17 November 2013). If you do this, you will be notified of your supervisor by mid‐January. Students who submit their applications later may have less chance of obtaining their first preference. Students commencing mid‐year should submit their application prior to the end of semester 1 (29 June 2014) in anticipation of a successful mid‐year completion of their BSc. The BSc(Hons) Program The 16 units of credit associated with the Honours program is a mixture of research and course work. It comprises four components: Honours Research Project This is a year‐long component and culminates in the submission of a research report. The research project is carried out under the supervision of a member (or members) of the academic staff. The research topic is assigned by the supervisor after consultation with the student. This booklet contains many potential supervisors and research projects.
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Honours Research Proposal The research proposal outlines the work that the student will undertake and why they are doing it. This must be completed in the semester that they begin work as it is intended to provide an early focus for the student on their project work. It may also form the basis of the student’s introductory research report chapter. Honours Seminars Two research symposia will be held during the Honours year – one at the beginning, and one towards the end of the year. Each student will give an assessed research seminar in both symposia, in the first one outlining their proposed project, in the second one outlining their achievements. Attendance at the weekly School Seminar series is compulsory. Although occasional absences may be unavoidable, they must be accompanied by an apology sent to the Seminar coordinator and a valid reason for your inability to attend. Students are required to maintain a seminar notebook which must be submitted for scrutiny. Special Topics in Biochemistry and Molecular Biology or Microbiology and Parasitology This takes the form of a critique of a research paper using other scientific literature for comparison and includes an oral presentation and a written report of the findings. The goal of this exercise is to develop the ability of students to analyse published scientific work critically and to analyse the development of scientific ideas. Special Topics in Chemistry Each student shall choose one of the following modules. Depending on enrolments, some modules may not be offered. More details (course profiles, timetabling etc.) will follow later.
Module 1 Organic Chemistry Module 2 Inorganic Chemistry Module 3 Physical Chemistry The selection of course work by honours students should be discussed with the student’s supervisor. The final choice is subject to approval by the Honours Director. Coursework Component In addition to research seminars students participate, on a regular basis, in additional events that will provide additional skills as a successful scientist. They include eg. a course on scientific writing and seminar debriefing sessions. These events serve also as regular contact events with the School and improve the cohort experience. Administration of the Honours Program The Molecular Biosciences Honours program is coordinated by Dr James Fraser ([email protected], 3365 4868), Professor Roy Hall ([email protected], 3365 4647) and Dr Gene Tyson ([email protected], 3365 3829). The Chemistry Honours program is coordinated by Dr Joanne Blanchfield ([email protected], 3365 3622). Enquiries regarding the program should be directed to either staff member in the first instance. Administrative assistance is provided by Louise Nimwegen, ([email protected], 3365 3509) or Tammie Fair, Manager, Coursework Academic Administration ([email protected], 3365 7976).
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Summary for BSc(Hons) If you wish to commence BSc(Hons) in 2014 you should address any general enquiries to either of the staff members mentioned above. Even if you already have a firm idea about the supervisor you are likely to nominate as your first preference, consult widely with members of the academic staff to find out more about the projects being offered and the style of work involved. Remember, your first preference may not ultimately be your allocated supervisor, so it is important to be aware of alternative projects. Be aware that some details of projects being offered may change between the time when this booklet was prepared (July 2013) and your commencement time. For students commencing in February, lodge your application form with your list of project preferences at 68‐316 before Christmas. You do not have to (and should not) wait for your examination results to be released before submitting the form. Preferences should indicate three different supervisors or combinations of supervisors in the case of joint projects. Please note: the principal supervisor must be (a) an academic staff member of the School; (b) a research staff member of the School who holds an external competitive research fellowship, (c) an affiliate academic staff member of the School; (d) an adjunct academic staff member of the School, or (e) a Head of School‐approved employee of a research institute or industry. For students commencing in July, indicate your likely mid‐year enrolment to the Honours Director during Semester 1, 2014. Lodge your application before or during your mid‐year examinations. Please provide a contact phone number and address or email address. Dr James Fraser, Professor Roy Hall, Dr Gene Tyson Molecular Biosciences Honours Program Directors Dr Joanne Blanchfield Chemistry Honours Program Director August 2013
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PROFESSOR STEPHEN BARKER Phone: 07 3365 3303 Email: [email protected]
Biology and control of lice and ticks, and the pathogens that lice and ticks transmit to humans
Project 1. New public health strategies for Louse‐Borne Epidemic Relapsing Fever, which is caused by the spirochaete bacterium Borrelia recurrentis, in Ethiopia: is eradication desirable and/or feasible? Borrelia recurrentis, the spirochaete bacterium that causes epidemic‐relapsing‐fever, is transmitted to people by the body louse, Pediculus humanus. Epidemic‐relapsing‐fever is usually fatal if not treated. Epidemic‐relapsing‐fever is often one of the top 10 reasons for admission to hospital in the Horn of Africa, particularly Ethiopia. New public health strategies are needed for this disease which has been eradicated in all countries, except the countries in the Horn of Africa, Ethiopia, North Sudan, South Sudan, Eritrea and Djibouti. But is eradication desirable and/or feasible?
Project 2. New diagnostics for the Ixodes ticks of Australasia. The current diagnostic guide to the 24 species of Ixodes ticks in Australasia was made half a century ago and is woefully inadequate. A new diagnostic guide for the Ixodes ticks of Australasia, that combines genetic and morphological diagnostics is feasible and needed.
Project 3. Assembly of the genome sequence of the head louse, Pediculus capitis. In 2010, my colleagues and I sequenced, assembled and annotated the nuclear genome of the body louse, Pediculus humanus (Kirkness et al. PNAS 107, 12168‐12173). Last year we sequenced the genome of sister‐species of the body louse, the head louse Pediculus capitis. This genomes is remarkable because it is so small for a metazoan animal (ca. 110 megabases) and because the introns are few and short in this genome.
Project 4. Phylogeny of soft ticks. Join the International Tick Tree of Life Project. Phylogeny (evolutionary history) of ticks predicted from the nucleotide sequences (mitochondrial and SSU rRNA). Students will sequence part of the mitochondrial genomes of 1 or 2 interesting ticks from Africa and then use a computer to predict the evolutionary tree of
the ticks.
Bahir Dah, Ethiopia. A focus of Louse‐borne Relapsing Fever
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PROFESSOR PAUL BERNHARDT Phone: 07 3365 4266 Email: [email protected]
Our research efforts are concerned with coordination chemistry of relevance to biology, analytical science and technology. Students interested in any of these areas of research should contact Prof. Bernhardt for a more detailed project description.
(a) Novel ligands that stabilise complexes in unusual oxidation states We are working on ligands that are capable of stabilising metals in unusually high oxidation states (Cu(III), Fe(IV) etc.). Understanding how these ligands achieve this stabilisation and avoid decomposition pathways (sacrificial ligand oxidation) is a central goal of this project. Relevant Publication 1. M. Akbar Ali, P.V. Bernhardt,
M.A.H. Brax, J. England, A.J. Farlow, G.R. Hanson, L.L. Yeng, A.H. Mirza, and K. Wieghardt Inorg. Chem., 2013, 52, 1650.
(b) Copper complexes as catalysts for atom transfer radical reactions Since the discovery in 1995 that the simple Cu(I) complex [Cu(bipy)2]
+ (bipy = bipyridyl) is capable of generating organic radicals from simple alkyl halide precursors, similar complexes have been used extensively in so called atom transfer radical polymerisation, a major area of polymer synthesis. The mechanism by which the radical is produced and the influence of solvent remains controversial. This project will use spectroscopic and electrochemical methods to understand the reactivity of these simple but highly reactive compounds. Relevant Publications 1. C.A. Bell, P.V. Bernhardt and M.J. Monteiro, J. Am. Chem. Soc., 2011, 133, 11944. 2. T.J. Zerk, P.V. Bernhardt, Dalton Trans. 2013, DOI 10.1039/C3DT51100F
(b) Enzyme Electrochemistry Enzyme electrode biosensors are devices that comprise a redox active enzyme integrated with electronic circuitry to give real‐time quantitative analysis of chemical compounds in biological fluids or the environment. The current that is generated by the oxidation or reduction of the substrate provides a quantitative measure of the substrate concentration (see below). This project will involve the electrochemical investigation of metalloenzymes currently available within in our group.
S OHS OHS OHS OHS OHS OHS OHS OHS OHS OH
Au electrode
2 Cyt cOX
2 Cyt cRED
SDHRED
SO32- H2O+
2H+ +
2e-
membrane
bulk solution
SO42-
SDHOX
S OHS OHS OHS OHS OHS OHS OH
inner membranesolution
Scheme 2
Relevant Publications 1 P.V. Bernhardt Chem. Commun. 2011, 47, 1663. 2. P. Kalimuthu, S. Leimkuhler, P.V. Bernhardt, Anal. Chem. 2012, 84, 10359.
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Energy minimised model of HPV discontinuous epitope displayed on a hexaphenylbenzene scaffold.
DR JOANNE BLANCHFIELD Phone: 07 3365 3622 Email: [email protected]
Synthesis of Revolutionary Synthetic Vaccine Constructs (project with Professor Paul Burn)
In collaboration with Dr. Graham Leggatt (TRI) and Professor Paul Burn we are building fully synthetic constructs that display antigenic peptides or carbohydrates from HPV, HIV and Staphylococcus aureus. For details of the project please contact Joanne Blanchfield or Paul Burn.
This project would involve:
organic synthesis
carbohydrate synthesis
solid phase peptide synthesis
cell culture and plasma stability assays and aseptic techniques
assay development and molecule characterisation including use of HPLC, LC/MS, NMR, GC/MS equipment.
Bioavailability of Natural Products from Herbal Extracts (project with Professor James De Voss)
Herbal remedies are a major source of medical treatment for much of the world’s population. Unfortunately, little is known about the fate of the natural products in the extracts or which, if any, are biologically active. We are offering a project that uses a cellular model of the small intestine (Caco‐2 cell monolayers) to investigate which natural products are likely to enter the blood stream after oral intake of some popular herbal remedies. We also look closely at what changes the compounds undergo during digestion and absorption.
Use of preparative and analytical HPLC equipment to isolate potentially active compounds from herbal extracts.
Use of NMR and IR spectroscopic techniques and MS to characterise and identify the compounds isolated.
Culturing and maintaining human Caco‐2 cells under aseptic conditions.
Performance of in vitro biological assays to determine permeability (Caco‐2 cell assay), stability (CC2 homogenate assay, plasma stability) assays.
Analytical analysis using LC/MS and HPLC of the solutions resulting from the in vitro assays.
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DR MIKAEL BODEN Phone: 07 3365 1307 Email: [email protected]
Using bioinformatics and high‐throughput data to explain molecular biology Bioinformatics is a main driver of next–generation molecular biology. Smart integration of data, produced by emerging high‐throughput technologies, enables us to capture, and understand DNA, RNA and proteins in context: if they interact, fold, regulate, catalyse, modify or translocate (to mention but a few functions) across multiple species, tissues and developmental time points. My research aims to develop bioinformatics methods and apply them to further our understanding of a range of open problems in genomics, molecular and systems biology (exemplified below). In doing so, we actively collaborate with structural and cell biologists, protein engineers and genetics researchers.
Genomic features underlying triplet expansion associated genetic defects Expansion of nucleotide repeats underlies several genetic diseases such as Friedreich ataxia, fragile X syndrome and Huntington’s disease. Through genomics and systems biology approaches, leveraging emerging (next‐gen sequencing) data sets, this project will investigate features that determine the probability of a repeat to undergo expansion. (With Suresh Balasubramanian at Monash University.)
The meta‐structure of regulatory networks The combination of chromosome conformation with DNase hypersensitivity data has the potential of revealing interactions amongst target genes, complementing analysis of DNA binding of regulatory factors. This project will tap the burgeoning ENCODE repository to investigate a “spatial map” between DNA binding sites of specific co‐regulatory proteins (in a relevant cell type).
Building phosphorylation maps: from structure to system‐wide networks Data on post‐translational modifications range from detailed molecular binding events to low‐resolution system‐scale networks. This project will study how heterogeneous data sets (eg. binding motifs, structures and interaction networks relevant to phosphorylation) with dependencies (eg. between similar kinases and similar substrates) can be integrated, at different scales and deal with scarcity of data. (With Bostjan Kobe.)
Using statistical machine learning to evolve biocatalysts Proteins like the P450 enzymes are highly versatile biological catalysts with potential to improve the efficiency of many chemical processes. This project will use machine learning and statistical analyses to reveal how to redesign proteins to be thermostable based on the sequence‐structure examples nature has refined over millions of years (with Elizabeth Gillam).
All projects involve some computing, though the extent can be varied greatly. You are expected to have some programming skills, an analytical ability and above all scientific curiosity.
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PROFESSOR MELISSA BROWN Phone: 07 3365 4622 Email: [email protected]
Molecular Genetics and Biology of Breast Cancer Breast cancer is the most common cancer in women and results from abnormal expression or function of multiple tumour suppressor genes and oncogenes. Our laboratory is interested in the regulation and function of a number of breast cancer‐associated genes including those encoding BRCA1, BRCA2, and a range of miRNAs. We use a wide variety of molecular and cellular techniques to study how the expression of these genes is regulated and to examine the molecular and cellular consequences of disrupting their function in breast epithelial cell‐lines and the mammary gland of mouse models.
Project 1: Regulation of the Breast Cancer Susceptibility Gene BRCA1 This project will involve identifying novel regulatory elements controlling the expression of the BRCA1 gene. We are especially interested in the 3’UTR of BRCA1 and miRNAs that target this region. This project will involve elucidating the structure, function and clinical relevance of functional elements in the BRCA1 3’UTR. These elements have the potential to form the basis of improved pre‐symptomatic diagnostics for breast cancer.
Project 2: Regulation of MicroRNA Genes in Advanced Breast Cancer The aim of this project is to identify and functionally characterize miRNA promoters and their downstream target genes. Particular interest will be given to miRNAs that may be susceptible to aberrant epigenetic regulation. These miRNA have the potential to be novel biomarkers for the identification and management of patients that are susceptible to advanced breast cancer.
Project 3: Molecular and Cellular Consequences of Disrupting Breast Cancer Genes The aim of this project is to understand how changes in the regulation or function of breast cancer genes results in the development of breast cancer. This project will involve examining the effect of increasing and decreasing the expression of normal, variant and mutant forms of breast cancer genes on the expression of genes, including miRNAs, in breast epithelial cells. These molecules have the potential to be targets of novel therapeutic agents to treat breast cancer. Techniques: Bioinformatics, gene cloning and mutagenesis, mammalian cell culture and gene transfer, reporter gene assays, real‐time PCR, Northern blotting, chromatin conformation assays, methylation specific DNA analysis, cell culture assays including cell proliferation and differentiation.
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PROFESSOR PAUL BURN UQ Vice Chancellor’s Senior Research Fellow Director – Centre for Photonics and Electronics (COPE) Website: www.physics.uq.edu.au/cope/ Phone: 07 3365 3778 Email: [email protected]
The research mission of the Centre for Organic Photonics and Electronics (COPE) is to take nanotechnology from the “bench to the market”. COPE contains state‐of‐the‐art synthesis laboratories, a Class 1000 clean room, device fabrication facilities, and a suite of instrument rooms for the characterization of materials and opto‐electronic devices. COPE has Honours research projects in all branches of Chemistry (organic, inorganic, materials, physical, and computation) giving a fantastic opportunity for you to develop your own interests and skills at the cutting edge of a technological area, e.g., solar cells, flat panel displays and lighting, plastic electronics, explosives sensors, fuel cells, and synthetic vaccines. Below is a snapshot of some of the projects on offer and I would be happy to discuss them with you.
Project 1: Plastic solar cell Man‐made global warming is a scientific fact and a key component of slowing and ultimately halting climate change is the provision of clean (non‐fossil fuel) energy. If we convert a proportion of the 1 kJ of solar energy that falls on each square metre of the Earth’s surface per second of every daylight hour into electricity [photovoltaics (PV)] it will make a dramatic effect on the world’s energy supply. Would you like to use your organic chemistry skills to create new polymers, dendrimers or small molecules that can be used in efficient, flexible, and light weight plastic
solar cells fabricated at COPE? Do your interests lie in studying structure using neutron scattering or would you like to apply computation to develop an understanding of why some materials work well and some do not, leading to new design criteria?
Project 2: Flat panel displays and lighting Lighting and displays based on organic light‐emitting diodes (OLEDs) have the potential advantages of cheap manufacturing, better power consumption, better colours, and ultimately being flexible. Imagine a TV screen that could roll up into your mobile phone! The best emissive materials are comprised of organometallic complexes. Would you like to apply your interest in synthetic inorganic chemistry and/or materials chemistry to develop new emissive complexes and/or poly(dendrimers) that can be incorporated into real OLEDs at COPE? OLEDs are made up of thin layers of organic and inorganic materials and what happens as they age is not well understood. An interest in physical chemistry would allow you to
make an important contribution to our understanding of how OLEDs degrade.
Project 3: Sensing explosives sensors How do we detect explosives in real time selectively and sensitively? Currently the most sensitive detectors for explosives are canines. At COPE we are developing in partnership with industry our own handheld technology. The explosive analytes are detected by fluorescence quenching. The project brings together synthetic organic chemists who design dendrimers for sensing explosives and spectroscopists to understand how the analytes are detected. Are you an organic chemist or physical chemist who would like to work in an interdisciplinary team?
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ASSOCIATE PROFESSOR BERNIE CARROLL Phone: 07 3365 2131 Email: [email protected]
RNA interference (RNAi) and gene silencing in Arabidopsis Gene silencing is a highly conserved process in plants and animals, and is of fundamental importance to developmental regulation of gene expression, defence against viruses, transposon silencing, adaptation to environments and genome evolution. We are using Arabidopsis thaliana as a model for studying the mechanisms of gene silencing in plants.
Systemic movement of gene silencing Remarkably, when gene silencing is triggered in cells of plants and animals, it can spread throughout the organism. We are using a forward genetic approach and map‐based gene cloning to further elucidate the mechanisms of systemic movement of gene silencing in Arabidopsis.
Intron splicing regulates gene silencing in Arabidopsis The role of introns has puzzled molecular biologists since their discovery in 1978. But we recently showed that intron splicing protects genes from being silenced in Arabidopsis. Additionally, when we mutate introns to compromise their splicing, they become potent inducers of gene silencing. Defective intron splicing has been associated with genetic diseases in both plants and humans. This project aims to further investigate the mechanism of intron suppression and intron activation of gene silencing in Arabidopsis.
Genetic engineering of insect resistance in plants based on RNAi We are using RNAi to engineer plant resistance to insect pests, and it has the immense potential for dramatically decreasing the use of toxic insecticides. In contrast to chemical insecticides, RNAi molecules can be designed to target specific insects, avoiding any deleterious effects on non‐target species in the environment.
Selected recent publications: Brosnan et al. (2007) Nuclear gene silencing directs reception of long‐distance mRNA silencing in Arabidopsis. PNAS 104, 14741‐14746. Gursanscky et al. (2011) Mobile microRNAs hit the target. Traffic 12, 1475‐82. Christie et al. (2011) Intron splicing suppresses RNA silencing in Arabidopsis. Plant Journal 68, 159‐167.
Image: GFP silencing (red areas) can be seen spreading systemically throughout the plant.
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DR JACK CLEGG Phone: 07 3365 4384 Email: [email protected]
Metallo‐Supramolecular Chemistry and Metal‐Organic Frameworks Metallo‐supramolecular chemistry bridges the traditional fields of organic and inorganic chemistry. By using self‐assembly the inherent physical and chemical properties of simple metallic and organic (ligand) components are brought together to form beautiful complex and functional architectures. In particular, we are interested in the design and synthesis of new materials with central cavities that are capable of selectively binding smaller molecules. Projects involve a combination of synthesis, characterisation, binding studies, Xray diffraction, spectroscopy, data analysis and investigations into physical properties and can be tailor to suit the particular interests of a student. Example projects are given below.
Trapping Guest Molecules in Metal‐Organic Frameworks Metal‐Organic Frameworks are a class of polymeric hybrid material formed from organic and metallic components. These materials have large surface areas and high porosity and are finding application in gas sequestration and separation technologies. Accordingly it is possible to trap a large variety of guest molecules inside them. In this project you will investigate the binding of different solvent molecules inside one of these frameworks to explore selectivity and potential separation applications.
New Metallo‐Supramolecular Architectures Careful consideration of the geometrical properties of metals and organic components allows for the construction of a variety of discrete “supermolecules” formed from the spontaneous aggregation of numerous predesigned components. These structures, often with central cavities, take numerous forms from two‐dimensional architectures such as triangular and square architectures to elaborate and beautiful three‐dimensional species such as tetrahedra and cubes. Changing the size, shape, properties and charge of the architecture allows for the selective encapsulation of different materials inside them.
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PROFESSOR JAMES DE VOSS Phone: 07 3365 3825 Email: [email protected]
My group is concerned with biological and synthetic chemistry and in particular with the application of chemical principles to the understanding of biological processes. Most projects are a blend of disciplines in bio‐organic chemistry: synthesis, structure determination, molecular biology, protein purification. A range of techniques is employed, ranging from the biochemical (e.g. PCR, gel electrophoresis) to the chemical (e.g. NMR, HPLC, GC/MS). The following areas illustrate the research in my laboratory but the exact project will be determined by the student’s interests.
Project 1: Cytochromes P450 P450s catalyse an amazing variety of oxidative transformations, ranging from simple alkene epoxidation all the way through to oxidative C‐C bond cleavage. They are of interest as they (i) are often unique enzymes in a biosynthetic pathway and as such represent new targets for chemotherapeutic agents or (ii) are extremely efficient catalysts that offer the potential of developing tailored oxidative catalysts for synthetic transformations. We are interested in understanding the mechanism of action of a number of P450s. One example is CYP61, a unique P450 involved in steroid biosynthesis in fungi and other pathogenic organisms. As such it represents a potential target for novel chemotherapeutics. CYP61 catalyses an unusual reaction for a P450, namely the dehydrogenation of an alkane to an alkene. However, essentially nothing is known about the exact structure of the substrate, the stereochemistry of the reaction or its mechanism. Projects in this area will involve the synthesis of mechanistic probes, the analysis of the products of enzyme‐catalysed reactions, characterisation of enzyme mutants and design and synthesis of inhibitors.
Project 2: Constituents of Medicinally Used Herbs Whilst herbal medicines are widely used and have a long history of such use, their chemical constituents are often poorly characterised. In collaboration with a local company we have embarked upon a program of phytochemical characterisation of a number of therapeutically prescribed herbs. The results have been surprising with a number of previously unknown compounds isolated from supposedly well‐characterised species. This project would involve the isolation, chromatographic purification and structure determination (especially employing 1D and 2D nmr) of the chemical constituents of selected herbs. The structures of some recently isolated compounds are given below.
Relevant Recent Publications 1. Slessor, Kate E.,Farlow, Anthony J., Cavaignac, Sonia M., Stok, Jeanette E., De Voss, James J. Oxygen activation by P450(cin): Protein and
substrate mutagenesis Arch. Biochem. Biophys.2011, 507154‐162. 2. N. J. Matovic, J. M. U. Stuthe, V. L. Challinor, P. V. Bernhardt, R. P. Lehmann, W. Kitching and J. J. De Voss The Truth about False Unicorn
(Chamaelirium luteum): Total Synthesis of 23R,24S‐Chiograsterol B Defines the Structure of the Major Saponins from this Medicinal Herb Chem. Eur. J. 2011 17, 7578‐91.
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ASSOCIATE PROFESSOR VITO FERRO Phone: 07 3346 9598 Email: [email protected]
My research interests encompass carbohydrate chemistry and medicinal chemistry, with a focus on the synthesis of compounds to probe and/or inhibit carbohydrate‐protein interactions involved in disease processes. Of particular interest is heparan sulfate (HS) and the development of HS‐mimetics as potential drugs for cancer and various other diseases. Previous work in this area resulted in the discovery of PG545, a potent inhibitor of angiogenesis and metastasis that recently entered Phase I clinical trials in cancer patients.
1. Development of a fluorometric assay for heparanase Heparanase is a glycosidase that cleaves HS in the extracellular matrix and facilitates metastasis of tumour cells and vascular remodelling associated with angiogenesis. PG545 is an example of a heparanase inhibitor with potent in vivo activity in metastatic and angiogenic models. Despite the advancement to clinical trials of inhibitors, heparanase research has been limited by the lack of a simple and robust assay for enzymatic activity. This project aims to address the situation by the synthesis of novel fluorogenic substrates for heparanase.
2. Synthesis of pharmacological chaperones for lysosomal storage diseases Lysosomal storage diseases (LSD) are caused by mutations in enzymes that degrade polysaccharides such as HS, resulting in the accumulation of undegraded substrate in the lysosomes of cells. Some patients may be treated with enzyme replacement therapy. Unfortunately, the replacement enzyme cannot cross the blood‐brain barrier and thus cannot treat the neurological symptoms associated with severe cases. The aims of this project are to develop small molecules for the treatment of LSD, which unlike enzymes, are capable of crossing the blood‐brain barrier and thus may offer relief of neurological symptoms. The compounds are designed to act as “chaperones” to protect the defective enzyme from degradation and restore enzyme activity to sufficient levels to alleviate symptoms.
3. Glycosylated liposomes for targeted delivery of siRNA Targeted delivery to a specific cell type is desirable to improve the effectiveness and specificity of siRNA for gene silencing. The aim of this project is to generate specifically glycosylated liposomes that will enable delivery of siRNA to particular cell types possessing receptors for these glycans.
4. Synthesis of inhibitors of virus‐cell attachment Many viruses, including HSV and HIV, use HS as an entry receptor or co‐receptor. This project will focus on the synthesis of novel HS mimetics that inhibit virus‐cell attachment and possess virucidal activity.
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DR JAMES FRASER Phone: 07 3365 4868 Email: [email protected]
Infectious Disease: Fungal Pathogenesis & Evolution Our research goals are to identify weaknesses in fungal pathogens that can be exploited as drug targets to combat life‐threatening systemic infections, and to discover new Cryptococcus neoformans virulence factors by identifying microevolutionary events that occur in its genome while infecting humans.
Antifungal development Every year, up to 1.5 million AIDS patients are infected by the pathogenic yeast C. neoformans. Up to 1 million of these die, making cryptococcosis one of the top three killers of AIDS patients worldwide. This high mortality rate is due to the absence of an adequate array of antifungal agents. We are using a wide array of techniques to identify new drug targets in C. neoformans in the hope of reducing this high mortality rate. We have already identified some excellent targets and potential therapeutic agents. Honours students working on this project will have the opportunity to employ a very large array of experimental techniques, ranging from the creation of mutants, performing phenotypic screens (including drug susceptibility), analysing gene regulation using transcriptome sequencing and, depending on the discoveries made, using a murine model of infection to test the efficacy of new antifungal compounds.
Evolution of a pathogen's genome Even if a patient survives an infection by C. neoformans, they are likely to suffer a relapse infection that is even more deadly within twelve months of treatment. These C. neoformans isolates have usually undergone chromosomal rearrangements, which we have shown to correspond with an increase in virulence that enables the relapse infection to occur. Through collaborators at Duke University Medical
Center and the Albert Einstein College of Medicine, we have acquired a large collection of such strains from individuals who have suffered repeated rounds of infection. We are investigating these strains to identify undiscovered virulence factors and potential vulnerabilities that we could employ in the development of novel therapeutic interventions. Honours students working on this project will use next‐generation sequencing technology to sequence whole genomes of clinical strains of interest, characterise chromosomal rearrangements, create mutants and investigate the effects of these mutations on virulence.
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PROFESSOR LAWRENCE GAHAN
Phone: 07 3365 3844 Email: [email protected]
Iron(III)‐Zinc(II) Complexes as Analogues of Phosphomonoesterases (With Associate Professor Gary Schenk)
We have for some time been interested in simple coordination complexes which mimic the active sites of metalloenzymes and we have published a number of papers and reviews on the topic. Whilst we have made heterobinuclear mimics of the phosphodi‐ and tri‐esterase enzymes like GpdQ the glycerophosphodiesterase from Enterobacter aerogenes (GpdQ) we have been less successful with ligands which model metal ion content (Fe(III)/Zn(II)) that mimics the active site of the enzyme purple acid phosphatase (PAP). An earlier attempt resulted in the ligand 2‐((2‐hydroxy‐5‐methyl‐3‐((pyridin‐2‐ylmethylamino)methyl) benzyl)(2‐hydroxybenzyl)amino)acetic acid (H3HPBA; see below), where we prepared an Fe(III)/Fe(III) complex with interesting magnetic and spectroscopic properties. Surprisingly, the complex was catalytically active towards phosphomonoesters. In this project we will tailor the ligand to have one pronounced zinc(II) binding site and a site specfic for iron(III). The project will involve ligand synthesis, structural and spectroscopic studies and an investigation of the kinetics of phosphate ester hydrolysis.
Boudalis, A K., Aston, R. E., Smith, S. J., Mirams, R. E., Riley, M. J., Schenk, G., Blackman, A. G., Hanton, L. R., & Gahan, L. R. Synthesis and characterization of the tetranuclear iron(III) complex of a new asymmetric multidentate ligand. A structural model for purple acid phosphatases. Dalton Transactions 2007, 5132‐5139.
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PROFESSOR MARY GARSON Phone: 07 3365 3605 Email: [email protected]
Bioactive Chemicals from Marine Sponges and Mollusks The research in my group focuses on the biological chemistry of natural products from marine and terrestrial sources. One quarter of the world’s drugs come from Nature, primarily from micro‐organisms and from rainforest plants. As terrestrial resources became overexploited, attention turned to the marine environment as an alternative source of novel bioactive metabolites. Honours projects are available which provide experience of: (i) isolation & structure elucidation of metabolites; (ii) small scale synthetic manipulation of isolated metabolites; (iii) marine chemical ecology; (iv) marine microbial chemistry. Fig. (a) Low temperature NMR study of plakortoperoxide A; (b) Terpene metabolites of Thuridilla splendens
Recent projects have involved studies on Plakinastrella clathrata sp.1 and on Verongid sponges that contain antimalarial or cytotoxic metabolites, on complex terpenes from nudibranchs of the genera Chromodoris2,3 and Thuridilla, and on complex polyketides isolated from the marine fungus Acremonium sp. Frequently in these projects, sub miligram amounts of metabolites are studied by NMR at 500 and 900 MHz. 1D and 2D NOESY data are combined with molecular modelling studies and/or 3JCH meaurements to determine the stereochemistry of isolated compounds. Chemical ecology studies explore the role of marine metabolites in chemical defense as either antifeedants,4 or as antifouling compounds, and use simple benchtop assays. Recent Publications:
1. Yong, K.W.L., Lambert, L. K., De Voss, J.J., and GARSON, M.J., ‘Oxidative processes in the Australian marine sponge Plakinastrella clathrata; isolation of plakortolides with oxidatively‐modified sidechains,’ J. Nat. Prod., 75, 351‐360. 2012.
2. Katavic, P.L., Jumaryatno, P., Hooper, J.N.A., Blanchfield, J.T., and GARSON, M.J., ‘Oxygenated diterpenoids from the Australian sponges Coscinoderma mathewsi, Dysidea sp. and the nudibranch Chromodoris splendida.’ Aust. J. Chem., 65, 531‐538. 2012.
3. Suciati, Lambert, L. K., and GARSON, M.J., ‘Structures and anatomical distribution of oxygenated diterpenes in the Australian nudibranch Chromodoris reticulata.’ Aust. J. Chem., 64, 757‐765. 2011.
4. GARSON, M.J., ‘Marine natural products as antifeedants, In Comprehensive Natural Products Chemistry II, Mander, L., Lui, H.‐W., Eds.; vol 4, Elsevier: Oxford, pp 503‐537. 2010.
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PROFESSOR IAN GENTLE Phone: 07 3365 4800 Email: [email protected]
Research in my group is focussed on the self‐assembly of materials at interfaces and is directed at two main areas of application: advanced materials for electrodes for batteries and supercapacitors; and the fabrication and characterization of thin‐film structures for organic light‐emitting diodes (OLEDs), photovoltaic solar cells and vapour sensors. We work closely with collaborators in the Centre for Organic Photonics and Electronics (COPE) and the ARC Centre of Excellence for Functional Nanomaterials. There are world‐leading facilities for this work available at UQ and external facilities that we use extensively. These include X‐ray and neutron reflectometry (facilities such as the Australian Synchrotron, OPAL Research Reactor and facilities in the UK are normally used for these measurements), X‐ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), small angle X‐ray scattering and X‐ray diffraction.
Conducting Polymer Materials for High Energy Batteries As alternative energy sources are increasingly being exploited as ways of providing sustainable, low‐carbon energy, the issue of storage is becoming ever more important. For applications such as the electric vehicle market there is a pressing need for batteries with higher energy density (that is, energy per unit mass) than is currently available. Coupled to this need is the ability for batteries to be able to be recharged rapidly and to
be durable enough to survive up to 1000 charge/discharge cycles. We have been exploring a number of technologies that show great promise for increasing the capacity and durability of batteries for this purpose. We realized in recent work the importance of confinement of active materials in a matrix for achieving good stability of batteries. To take this concept further, we intend to extend the confinement system from inorganic materials to polymeric materials, which are anticipated to facilitate chemical bonding within confinement for even superior durability of batteries. This project will be a systematic investigation of a conducting polymeric cathode system produced by soft‐templated polymerization in a micellar solution, involving spontaneous encapsulation of active storage materials inside polymer spheres, characterization of the structure and composition using Raman spectroscopy, X‐ray diffraction, FTIR spectroscopy, X‐ray photoelectron spectroscopy, thermogravimetric analysis, porosity measurement and finally electrochemical evaluation of the reversibility of the materials. The outcome is expected to be an understanding of the advantages of chemically bonded confinement compared to physical confinement.
Thin‐film organic optoelectronic devices Most organic‐based optoelectronic devices such as organic solar cells and light‐emitting diodes are based on multilayers of organic materials. In previous work we have discovered that diffusion between the layers is a crucial characteristic of such structures. Using neutron reflectometry we can sensitively and in real time measure the extent of diffusion in multilayer films. In this project we are interested in the structure of interfaces and the processes that occur at the interface between the organic layers and the inorganic materials of the electrodes (normally metals or metal oxides). The aim is to be able to develop more durable and efficient devices through understanding and control of these processes.
Confined sulfur in a new cathode material for
lithium sulfur batteries
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PROFESSOR ELIZABETH GILLAM Phone: 07 3365 1410 Email: [email protected]
Cytochrome P450 enzymes: Nature’s most versatile enzymes Cytochrome P450 enzymes are one of the most functionally versatile groups of biocatalysts known. They carry out diverse roles in all domains of life because they can catalyse an extraordinary range of chemical transformations on an unprecedented variety of substrates. Our group is interested in finding out how P450s work and how they can be made to work better. Projects in the Gillam lab involve cutting‐edge techniques in artificial evolution, protein design and high throughput screening, as well as fundamental methods of molecular cloning, genotyping, protein chemistry and metabolite analysis.
1. Artificial evolution of P450s for drug development and bioremediation. We are using artificial (or directed) evolution to engineer enzymes that are more efficient, robust and specialized than naturally occurring enzymes for application in drug discovery and development and cleaning up the environment. The approach we are using also allows us to explore the essential sequence and structural features that underpin all ~12000 known P450s so as to determine how P450s work.
2. Ancestral reconstruction of P450s, enzymes evolved to deal with the unknown Five P450s metabolise ~ 95% of all drugs to which humans are exposed as well as innumerable environmental chemicals ‐ an extraordinary range of substrates, many of which have not been present during evolution. We are studying how these enzymes have evolved such extreme substrate promiscuity by reconstructing ancestral precursors and evolutionary pathways.
3. P450s in brain: relevance to mental illness and neurodegenerative diseases (with Prof. Peter Dodd and Dr. Simon Worrall) P450s localised in mitochondria have recently been shown to contribute to the neurotoxicity of some drugs and can lead to oxidative damage to mitochondria. Genetic differences between individuals affect the expression of P450s in mitochondria and may contribute to susceptibility to diseases such as Alzheimer’s.
4. P450 Nanodiscs for biosensors (with Prof. Paul Bernhardt) Since P450s respond to such a variety of different substrates they are well suited for use as biosensors to detect trace environmental contaminants, drugs and other chemicals. We will formulate P450s into nanodiscs – minute protein‐bounded lipid bilayer discs – to characterise their electrical properties by protein electrochemistry. Our research suits students in biochemistry, molecular biology, chemistry, biotechnology, or bioinformatics who are interested in discovering how enzymes work, how to engineer them to provide clean green alternatives to chemical processes, and the molecular basis to the toxicity of drugs and other chemicals.
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ASSOCIATE PROFESSOR LISBETH GRONDAHL Phone: 07 3365 3671 Email: [email protected]
The primary research area of the Grondahl Group is biomaterials design and evaluation. All projects builds on Interfacial Science and Materials Chemistry fundamentals. Collaborations with other chemists, engineers and biologists at UQ enable the tailoring of projects to specific interests of students. The projects listed below are examples of what could constitute an honours project in the Grondahl Group.
Protein Adsorption to Well‐Defined Surfaces Many biomaterials possess suitable bulk properties; however, their surface properties are not ideal. The material surface characteristics influence the final type, orientation and conformation of adsorbed proteins and hence the subsequent cell‐surface interactions. Biomaterials with non‐ideal surface properties therefore frequently fail to perform appropriately in vivo leading to an extensive prolonged inflammation, fibrous capsule formation and implant rejection. Investigating the protein adsorption to surfaces with controlled surface features will advance the knowledge needed to design future generation biomaterials with optimal properties. This study involves surface modification of biomaterials as well as protein adsorption studies.
HAP nano‐composites Hydroxyapatite (HAP) is the main mineral phase of bone and teeth. In vivo the biomineralisation process occurs in the presence of biological macromolecules where the ion concentrations are too low for spontaneous nucleation and growth of crystals to occur. In addition, the morphology of the HAP crystal is affected by the presence of these biomacromolecules. In order to produce HAP nanoparticles suitable for composite bone biomaterials a better understanding of how to control size and shape is required. This study will investigate the nucleation and growth of HAP in the presence of macromolecules. It involves collaboration with Dr Kevin Jack (CMM).
Tailored matrices for temporal delivery of drugs in bone repair Non‐union and delayed union fractures are unable to heal by themselves and therapeutic options would therefore greatly benefit from delivery of bone‐growth inducing factors. Successful delivery of factors requires the development of drug delivery systems optimised for these molecules. Biodegradable gels can be used to encapsulate these bone‐inducing factors. Specifically, one project will investigate functionalisation of alginate with amino acids for tailoring the gel matrix and another project involves investigation of using LbL assemblies to control the drug release rate. The drug delivery systems will be characterised using a combination of microscopic techniques (optical, fluorescence, and cryo‐EM) and spectroscopic techniques (Fluorescence, FTIR) and their stability in a simulated body environment will be assessed. In addition, drug encapsulation efficiency and the drug release rate from the system will be optimised. This study involves collaboration with Dr Gwen Lawrie.
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ASSOCIATE PROFESSOR LUKE GUDDAT Phone: 07 3365 3549 Email: [email protected]
Branched‐Chain Amino Acid Biosynthesis: A target for drug discovery
Acetohydroxyacid synthase (AHAS) and ketol acid reductoisomerase (KARI) are the first two enzymes in the branched chain amino acid biosynthesis pathway. There is now a large body of evidence to support the hypothesis that the inhibition of this pathway can be used to discover new antibacterial and antifungal agents. The goal in this project is to discover and develop new inhibitors of AHAS or KARI using state‐of‐the‐art rational drug design techniques and X‐ray crystallography. We have been successful in using X‐ray crystallography to determine the three‐dimensional structure of AHAS (yellow crystals because of the presence of FAD) and KARI. We have also shown how a potent inhibitor of AHAS binds to the enzyme with nanomolar affinity, making it an excellent starting point for drug discovery. We have projects for honours students that could involve X‐ray crystallography, chemical synthesis, enzyme assay, small molecule screening, fragment screening, computer modelling, antibacterial or antifungal testing, and protein expression and purification (or any combination of the above). The work is currently funded by an NHMRC project grant.
O
OCH2CH3
S NH C
O
NH
N
NCl
OCH3
O
O
C
chlorimuron ethyl (CE)
S NH C
O
NH
N
NCH3
O
O
monosulfuronester (MSFE)
O O CH3
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PROFESSOR ROY HALL Phone: 07 3365 4647 Email: [email protected]
Areas of Research:
Studies on the molecular biology and pathogenesis of mosquito‐borne flaviviruses that cause diseases such as Japanese encephalitis (JEV), West Nile virus (WNV) and Murray Valley encephalitis virus (MVEV).
Studies on the immune response to JEV, MVEV and WNV and the design and evaluation of novel vaccines to these viruses.
Development of novel molecular and serological diagnostic assays for JEV and WNV.
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PROFESSOR PHIL HUGENHOLTZ DR GENE TYSON Phone: 07 3365 3822 Phone: 07 3365 3829 Email: [email protected] Email: [email protected] The Australian Centre for Ecogenomics is a research centre within the School of Chemistry and Molecular Biosciences focusing on culture‐independent investigation of microbial communities in environmental and clinical habitats. This approach is crucial to understanding the microbial world as most microorganisms are not culturable in the laboratory. Key molecular and imaging techniques are now available for high throughput and high resolution analysis of microorganisms in their native settings including metagenomics, metatranscriptomics, fluorescence in situ hybridization (FISH) and flow sorting. We are looking for motivated honours students to join our ranks on a number of exciting and cutting‐edge projects.
Environmental projects: Microorganisms drive all the major biogeochemical processes on earth. Only in the last few years has the molecular ecological toolkit become available to fully illuminate the microbial underpinnings of these processes. We have ongoing projects available to study the microbial community structure and dynamics of the following environments; alkaline segments of termite hindguts to identify populations of interest for cellulosic biofuel pretreatment, the sugarcane root microbiome for sustainable agriculture, coal seam methane formation waters to understand methane generation, and thawing permafrost soils to identify key populations involved in cycling of carbon.
Clinical projects: Perhaps not surprisingly most clinical research focuses on recognised pathogens. There is an increasing realisation, however, that most pathogens do not act in isolation with their host and that infections have ‘polymicrobial’ phenotypes. In fact it has been shown that some microbial species will compete with pathogens for resources and provide a beneficial effect to the host. We have a number of ongoing projects that will apply 16S rRNA gene pyrosequencing‐based (pyrotag) community profiling and population‐specific FISH imaging to a number of clinical samples. These include lung, skin and gut.
Reference: Hugenholtz, P. and G.W. Tyson. 2008. Microbiology: metagenomics. Nature 455(7212): 481‐483.
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DR ULRIKE KAPPLER Phone: 07 3365 2978 Email: [email protected]
My research is centred on how bacteria from various ecological niches transform inorganic and organic sulfur compounds, an area of research that has received a lot of attention in recent years as many sulfur compounds are toxic, malodorous and several are known to influence climate processes.
Many of the bacterial species involved in these processes are also of industrial interest for use in bioreactors that remove sulfur compounds e.g. from flue gas or other wastestreams and as a source of enzymes catalysing novel reactions. Bacteria oxidizing organic and inorganic sulfur compounds in soils are also crucial for making sulfur available for plant growth and thus are important in agriculture and soil management.
I am also interested in elucidating the role of metalloenzymes in bacterial pathogenesis. Molybdenum–containing enzymes can support anaerobic growth of bacteria which is important for survival in biofilms and in anaerobic niches of the human body.
The work carried out in my group is very diverse and includes bacterial physiology, gene regulation, some genomic biology, proteomics as well as protein purification and characterization by a variety of techniques including different types of spectroscopy. Projects can be tailored to your area of interest in as much as possible.
Projects offered in 2013/2014
Regulation of gene expression Regulation of bacterial sulfite oxidation – a novel role for extracytoplasmic function (ECF) sigma factors
Enzymes & their role in bacterial physiology Do metalloenzymes support virulence of human pathogens? Case study: Haemophilus influenzae Molybdenum enzymes
Friend or Foe? – Metabolic interactions between Streptococcus pneumoniae and Haemophilus influenzae
Environmental microbiology & applications
Some like it alkaline – Can we use alikaliphilic sulfur oxidizers to treat sulfur pollution?
Co‐supervision with Prof. Gordon Southam: “The growth of gold nuggets” – bacterial degradation of
thiosulfate gold complexes
If you find these topics interesting, but would like to work on other aspects of the projects, please contact
me – this list is not comprehensive and additional projects are available.
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ASSOCIATE PROFESSOR STUART KELLIE Phone: 07 3365 4613 Email: [email protected]
Signalling Molecules in Macrophages and Tumour Cells Interests in my lab are focussed on the molecules that regulate signalling in macrophages and other phagocytes, and in tumour cells. In phagocytes such as macrophages, acute and chronic stimuli induce a number of intracellular signalling genes to be expressed. These genes include molecules that potentiate activation, but also include molecules such as tyrosine phosphatases that can inhibit cell activation. My lab is interested in the interplay between the positive and negative regulators of cell activation in both macrophages and in tumour cells.
Projects currently available in my lab include:
Project 1: The Role of the Tyrosine Phosphatase DEP‐1 in Macrophage Motility and Activation We have recently shown that the tyrosine phosphatase DEP‐1 is upregulated in macrophages upon stimulation with inflammatory factors. Furthermore this protein regulates macrophage membrane activity, motility and chemotaxis. This project will investigate the molecular mechanisms underlying this.
Project 2: The Regulation of the Tyrosine Phosphatase DEP‐1 by Noncoding RNA in Tumour Cells and Macrophages We have recently identified several noncoding RNA molecules associated with the DEP‐1 gene in mammary cells. This project will investigate whether these ncRNA can regulate the DEP‐1 gene in these cells. The presence of ncRNA in macrophages and their potential role in regulation of the DEP‐1 gene will also be investigated.
Project 3: Functional Analysis of Macrophage Genes Induced by Respiratory Syncytial Virus The furin‐like family of peptidases are upregulated by viruses in macrophages and other cells. This project will investigate the role of members of the furin‐like family in the infectious spread of Respiratory Syncytial Virus.
Project 4: Structural and Functional Studies of Macrophage Signalling Molecules (with B Kobe and J Martin and M Sweet). The Kobe and Martin laboratories have solved the structure of a number of macrophage proteins. This project will use the structural knowledge gained to investigate the function of these proteins in macrophage activation.
Project 5: The Use of Yeast Cells Expressing Mammalian Signalling Molecules as Biological Screens for Potential Therapeutic Targets (with James Fraser). When signalling molecules such as tyrosine kinases are inducibly expressed in yeast such as Saccharomyces pombe, they result in inhibition of growth of the cells. This project will involve cloning several signalling molecules into yeast, assessing the effect on proliferation, and establishing these cells as biological screens for inhibitors.
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PROFESSOR ALEXANDER KHROMYKH Phone: 07 3346 7219 Email: [email protected]
RNA virology laboratory study molecular mechanisms of virus RNA replication and virus‐host interactions with the main focus on the West Nile virus (WNV) and more recently on Chikungunya virus. WNV belongs to Flaviviruses, a group of highly pathogenic positive strand RNA viruses causing major outbreaks of potentially fatal diseases and affecting more than 50 million people each year. Chikungunya virus is a member of Alphaviruses and has recently caused large outbreaks of devastating arthritis disease in Reunion Island and Asian countries. We are aiming at a better understanding of how these viruses replicate in the host and cause disease, which will help in the development of antiviral drugs. In addition, we develop and evaluate vaccine candidates to prevent infection and outbreaks. The following projects are available:
1. Role of Small Subgenomic RNA in Flavivrus Pathogenicity. We recently identified a small subgenomic RNA produced from the 3’ untranslated region of the viral RNA in cells infected with a variety of flaviviruses. This subgenomic flavivirus RNA (sfRNA) is the product of incomplete degradation of genomic RNA by cellular ribonucleases and is required for viral response. We will elucidate the function of sfRNA in the viral life cycle and identifyi cellular and viral interaction partners of sfRNA.
2. Virulence Determinants and Host Innate Immune Response to West Nile Viruses. We have shown previously that WNV is able to evade innate immune response with more virulent strain able to do it more efficiently. There are a number of projects available in collaboration with leading overseas groups (M Diamond, USA; M Gale, USA; and S Akira, Japan) as well as local virologists (Roy Hall, SCMB) which will focus on the mechanisms by which pathogenic (New York 99) and non‐pathogenic (Kunjin) strains of WNV interact with the host innate immune response and how these interactions determine outcome of infection.
3. KUN Virus DNA‐Based Vaccine against Pathogenic Flaviviruses. We recently published the development of a highly effective DNA vaccine against WNV which involves the production of single round infectious particles and has been shown to induce high antibody levels in mice and horses. The project will continue in collaboration with Dr. Roy Hall at SCMB and Dr. Andreas Suhrbier at the QIMR to extend the technology to development of vaccines against other medically important flaviviruses, dengue and Japanese Encephalitis.
4. The role of miRNAs in Flavivirus‐Mosquito Host Interactions. In collaboration with S Asgari (SBMS) we have identified a first miRNA produced by WNV and have shown that it targets a transcription factor in mosquito cells that is essential for virus replication. This project is aimed at further investigations of the role of WNV‐induced/produced cellular and viral microRNAs (miRNA) in determining the outcome of virus infection in mosquito vector.
5. Innate immune response to Chikungunya virus. This project is a collaboration with Andreas Suhrbier (QIMR) and is focused on understanding how the innate immune response to this infection relates to virus‐induced disease. Using mouse model of the disease developed at QIMR the studies will employ a wide range of mouse strains deficient in expression of various factors involved in innate immune response and cell lines derived from them to identify host factors involved in response to Chikungunya virus infection and in the development of virus‐induced arthritis.
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PROFESSOR BOSTJAN KOBE Phone: 07 3365 2132 Email: [email protected]
Structural Biology of Infection and Immunity Our lab focuses on understanding important biological processes including infection and immunity at the molecular and structural levels. We are using an integrated approach combining determination of three‐dimensional structures (with emphasis on X‐ray crystallography) with computational techniques, methods for quantitative evaluation of molecular interactions, protein chemistry and molecular biology.
Projects include:
Structural Studies of Proteins Involved in Mammalian and Plant Innate Immune Pathways The aim of this project is to use structural biology to understand the molecular events occurring in (i) Toll‐like receptor signalling pathways, with implications for infectious and inflammatory disease, and cancer; and (ii) innate immune pathways in plants (plant disease resistance), with the long‐term goal to make plants resistant to a variety of pathogens. The projects involve protein expression, purification, crystallization, structure determination, interaction studies and functional studies using site‐directed mutant proteins.
Structural Studies of Proteins Involved in Bacterial Pathogenesis The aim of this project is to use structural biology to understand the processes of bacterial pathogenesis by different bacterial pathogens. The projects involve protein expression, purification, crystallization, structure determination, interaction studies and functional studies using site‐directed mutant proteins.
Understanding the Mechanism and Specificity of Nucleo‐Cytoplasmic Transport The aim of this project is to understand the mechanism of transport of proteins into the nucleus, including the specificity and regulation, with the long‐term goal of manipulating this essential process. The projects involve protein expression, purification, crystallization, structure determination, and interaction studies, as well as bioinformatics/computational aspects.
Linear Motifs in Signal Transduction Linear sequence motifs are recognized in many signalling processes, including protein kinases, MHC molecules involved in the immune response, and nuclear transport factors. This computational project focuses on developing bioinformatic tools that integrates structural information with sequence and other available data.
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DR GWEN LAWRIE Phone: 07 3365 7848 Email: [email protected]
Projects are available in the field of chemical education in my group and focuses on how students construct and apply their understanding of chemistry concepts. Situated at the interface between the fields of chemistry and educational psychology, current projects involve research into the processes of knowledge construction, complex reasoning and higher‐order thinking skills. Educational research methodologies will be applied to collect and analyse quantitative and qualitative data (these projects follow same processes as bench chemistry projects!).
1. The role of student‐generated visual representations in the acquisition of chemical literacy. Visual representations of chemical concepts and processes are used widely in learning and teaching chemistry. Passive engagement with these images by students supports the construction of incomplete mental models. Recent evidence indicates that student‐generated visual representations may introduce a more effective way for students to construct their understanding of chemical concepts, structures and acquire associated terminology. In this project, student conceptual understanding, perceptions and language will be evaluated and data will be collected through interviews and artifacts of student work (qualitative data).
2. The investigation of formative feedback and activities that introduce cognitive conflict to address strongly held misconceptions in chemistry. (In collaboration with Dr Tony Wright, School of Education) Students typically construct their mental models of chemical concepts based on their prior knowledge and experiences that have developed across the primary, secondary and tertiary science learning contexts. There are a number of well‐characterised chemistry misconceptions reported in the literature that are strongly held over time despite encounters with situations which challenge these conceptions. In this project, the role of and form of formative feedback delivery, in combination with online activities that challenge conceptions, will be explored to investigate the factors that influence conceptual change. Data will be collected through both stimulated‐response interviews and student self‐explanations while they complete online interventions.
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DR SHIH-CHUN (LAWRENCE) LO Phone: 07 3365 7657 Email: [email protected]
Organic materials and Nanotechnology
We are focusing on developing new classes of nanomaterials mainly for energy related applications, such as photon‐induced water splitting (for H2 generation), solar cells, and organic light emitting diode (OLEDs) as well as bio‐applications. Honours students will learn how to design, synthesise and characterise these frontier functional materials.
Project 1: Clean hydrogen fuel generation
The use of hydrogen gas as a renewable and clean fuel has been one of the most exciting research fields, in particular, direct hydrogen creation from water driven by sunlight. Developing efficient and long‐lasting water‐splitting photosensitisers and catalysts has been the key challenge for the technology. The project is to synthesise and characterise new water‐splitting photosensitizers for effective light absorption and catalysts for efficient water decomposition.
Project 2: Advanced materials for opto‐electronics (e.g., OLEDs, solar cells, and photodiodes) The project is to develop new electro‐active materials for OLEDs, solar cells, and photodiodes for our next generation flat‐panel displays (e.g., mobile phones, tablets, monitor displays and TVs for the superior display‐quality and superb energy saving), renewable energy generation and high‐sensitive detectors. The project will involve organic/organometallic and physical chemistry, and students will learn how to fabricate and
characterise these devices by closely working with device physicists.
Project 3: Biomaterials for imaging and treatment Photodynamic therapy (PDT) has been developed to provide non‐invasive (compared with conventional surgery) and less side effects (compared to chemotherapy) for cancer treatment. PDT can be accurately targeted, and repeatedly administered without the total‐dose limitations related with radiotherapy and result in little or no scarring after healing. To facilitate the advantages of PDT, we are developing novel bio‐compatible photodynamic therapy agents for deeper tissue treatment with less photodamage with effective two‐photon absorption activities.
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PROFESSOR ALAN MARK Phone: 07 3365 4180 Email: [email protected] Website: http://scmb.uq.edu.au/staff/alan-mark
The group uses computer simulation techniques to model the dynamic behaviour of biomolecular systems such as proteins, carbohydrates, nucleic acids and lipids. In addition to software and force field development we use simulations to understand how protein and peptides assemble into functional complexes and interact with potential drug molecules or biological membranes. We look for students with a background in structural biology, physical chemistry, physics, pharmacology or computational science interested in working at the interface between different disciplines.
Projects include: The activation of cytokine receptors Cell surface receptors such as the growth hormone receptor and the epidermal growth factor receptor play critical roles in cell regulation. Molecular dynamics simulation techniques will be used to characterize the conformational changes within the extracellular and transmembrane domains that accompany the binding of the cytokine (growth hormone, erythropoietin, prolactin or epidermal growth factor) to its receptor thereby shedding light on the mechanism of action of cytokine receptors in general. (Dr. David Poger) Anti‐microbial peptides Antimicrobial peptides (AMP) are small cationic peptides that act as modulators of the innate immune response and/or direct anti‐infection agents. AMPs have attracted much interest as they have the potential to form a new class of antibiotic agent capable of combating bacterial resistance to current drugs. Cytolytic AMPs act by directly disrupting the cell and have remained effective for millions of years. However, to be developed into effective therapeutics the molecular properties that give rise to cell specificity must be understood in detail. Using computer‐modelling techniques you will study the peptides in different environments in order to identify factors that may further improve discrimination between bacterial and mammalian cell lines. (Dr. David Poger)
The group also works on a variety of other problems that could be undertaken as honours projects. These include the development of novel methodology for computational drug design, simulating peptide folding and assembly; the nucleation and growth of amyloid fibrils; the mechanism of action of the multidrug transporters and the mechanism of action of glycopeptide antibiotics.
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ASSOCIATE PROFESSOR ROSS McGEARY Phone: 07 3365 3955 Email: [email protected]
My research interests lie in the areas of biological/medicinal chemistry and synthetic methodology. I hold a joint appointment with UQ’s School of Pharmacy. Several projects are available which are suitable for Honours students, and these students will gain experience in synthetic organic chemistry, inhibitor design, structure elucidation, instrumental techniques and bioassays, if appropriate. I encourage students to contact me to discuss these projects. New projects are available from time to time, and additional information can be found at my website: www.scmb.uq.edu.au/academicstaff/mcgeary/index.html
Designing New Reactions We have been exploring the synthetic utility of 2‐mercaptobenzothiazole 1, and we have recently developed a simple and mild method for the conversion of epoxides into alkenes 2, with retention of stereochemistry. Previous methods for achieving this transformation employed harsh reaction conditions that were incompatible with many functional groups. We are currently examining the scope and limitations of this new reaction and we are investigating related reactions to convert �‐halo ketones to alkynes 3, to prepare vinyl sulfones for cycloaddition reactions 4, and to develop mild and efficient chemistry for malonate‐type ester preparations 5.
The Roles of Substituents and New Catalysts in the Claisen Rearrangement The rearrangement of allyl vinyl ethers 8 to give �,�‐unsaturated carbonyl derivatives 9 (the Claisen rearrangement) has proven to be a general and reliable way to introduce contiguous chiral centres into carbon frameworks. As such, the Claisen rearrangement has been widely used in the synthesis of complex natural products. Studies have shown that the rate of the Claisen rearrangement can be greatly enhanced by electron‐withdrawing substituents, such as a nitrile group at the allylic carbon adjacent to the oxygen atom in 8. This promises to significantly extend the scope of this reaction. Recent work from our lab has revealed new methodology for performing the Claisen rearrangement, either thermally or with Lewis acid catalysts. This project will examine the Claisen rearrangement of allyl vinyl ethers 8, derived from allylic alcohol or cyanohydrins. Aromatic substrates will also be examined.
Medicinal Chemistry (1): Design and Synthesis of Inhibitors of Purple Acid Phosphatases (In collaboration with A/Prof Luke Guddat and A/Prof Gary Schenk) Purple acid phosphatase (PAP) is a binuclear metalloenzyme that occurs in animals, plants, fungi and some bacteria. The enzyme contains either an FeIII‐FeII, FeIII‐ZnII or FeIII‐MnII binuclear centre in the active site. While all of the biological roles of the PAPs have yet to be elucidated, it is clear that, in mammals, they play an important role in bone resorption (osteoporosis). Inhibition of the human enzyme is therefore a promising possible strategy for the treatment of this disease. The crystal structures of a number of variants of this enzyme have been determined and some progress has been made on discovering the likely mode of action of these inhibitors. An opportunity now exists to use this knowledge to design inhibitors and better understand the mechanism of action of the enzyme. This project will involve organic synthesis, enzyme assays, computer modelling and drug design.
Medicinal Chemistry (2): Design and Synthesis of Inhibitors of Metallo‐�eta‐lactamases (In collaboration with A/Prof Gary Schenk) For details of this interdisciplinary project targeting drug resistance, see the description listed under Associate Professor Gary Schenk.
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DR EVAN MOORE Phone: 07 3365 3862 Email: [email protected]
Our research focuses on exploiting the unique properties of the Lanthanide series. These metals are used in high‐end technological applications, including high strength magnets (Nd), contrast agents for medical imaging (Gd), and as catalytic converters for car exhaust (Ce) to name a few. Current research projects relate to the development of organic Ln(III) complexes for applications in several areas
1. Luminescent Imaging Ln(III) cations have well known luminescence properties. Their emission bands are very sharp, as a result of the 4f orbitals involved. Moreover, their emission is much longer lived (μsec to msec) when compared to organic chromophores (nsec), allowing for improved sensitivity using time gating techniques. In particular, we are interested in developing complexes of Yb(III) and Nd(III), which have emission in the Near Infra‐Red (NIR) region. These wavelengths allow for the improved depth penetration of light through biological tissues, for applications in NIR imaging.
2. Photodynamic Therapy Due to their high atomic mass and paramagnetism, Ln(III) cations exert a strong influence on the efficiency of intersystem crossing (eg. excited singlet to triplet state conversion) for organic molecules by enhancing
spin‐orbit coupling. The long‐lived excited triplet state of organic molecules can act as a photosensitiser for triplet ground state (3Σg) molecular oxygen, leading to formation of excited state (1Δg) singlet oxygen. This highly reactive molecule causes significant oxidative stress and damage to cellular structures, forming the basis of photodynamic therapy (PDT). We are exploring the use of Ln(III) complexation as a way of influencing the properties of existing organic photosensitisers used for PDT, and developing new Ln(III) based compounds with enhanced efficacy.
3. Lanthanide Frameworks Coordination Polymers (CP’s) (or Metal Organic Frameworks – MOF’s) are crystalline materials built from repeating units of (typically) rigid organic ligands interconnected by metal cations to form 1‐, 2‐, or 3‐D structures. Our research involves the construction of CP/MOF's utilising Ln(III) metal cations in combination with organic ligands such as aromatic N‐oxides. We are interested in the structural, magnetic, and luminescent properties of these materials, together with their applications in important industrial processes such as gas sorption, separation and storage.
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PROFESSOR PETER O’DONOGHUE Phone: 07 3365 2584 Email: [email protected] Websites: www.scmb.uq.edu.au/pod/ parasite.org.au/introduction/index.html
My research concentrates on protozoan organisms of Australia, especially those implicated in zoonotic disease, symbiotic relationships, and contamination of water supplies. Honours projects are tailored for individual students on the basis of their interests, anticipated career, project novelty and ‘do’‐ability. Students work on topical problems in medical, veterinary or wildlife parasitology using a range of conventional and contemporary technologies.
Symbiogenesis in Herbivores Herbivorous animals rely on endosymbiotic micro‐organisms to aid in their fermentative digestion. Studies in Australia have revealed novel ciliates and flagellates in ruminants, marsupials and insects. Many protozoa have also harboured unique symbiotic bacteria. This project aims to identify these hypersymbiotic partners by ultrastructural and molecular studies.
Coccidiosis in Mammals Little is known about the coccidian parasites of Australian animals. Native animals would be expected to have endemic parasite species (due to their long geographic isolation) while introduced animals would have cosmopolitan/exotic species. This project will test co‐evolutionary theories.
Haematozoa in Wildlife Australian animals are infected by a range of vector‐borne protozoa, including trypanosomes (mammals and reptiles), haemogregarines (reptiles), haemosporidia (mammals, birds) and piroplasms (mammals). Studies with wildlife and museum collections aim to identify these haemoprotozoa, determine their pathogenic potential and infer phylogenetic relationships.
Testate Amoebae of Australia Little information is available on the taxa of freshwater amoebae occurring in Australia despite their contribution to water quality by consuming bacteria and algae. This project will collect testate amoebae (those with external shells) from local water supplies and identify them by light and electron microscopy.
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ASSOCIATE PROFESSOR MARK RILEY Phone: 07 3365 3932 Email: [email protected]
The study of the antiferromagnet CuB2O4
Crystals of copper meta‐borate (CuB2O4) contains planar CuIIO4 species separated by BO4 tetrahedra. It is an
antiferromagnetic material below TN = 20K and shows a number of remarkable properties. These include a claimed ability control of the crystal chirality by a magnetic field [1], the control of the magnetization direction by an electric field and the observation of a “Giant Optical Magneto‐electric Effect” [2]. This latter effect results in the crystal having the intriguing ability to transmit light in one direction, but not in the opposite direction. The project can contain either / both experimental (spectroscopy and synthesis) and theoretical aspects of material science and can be tailored to a student’s particular interest.
The optical properties of Tanzanite Tanzanite is a very rare gemstone that occurs only in a small area on the slopes of Mt Kilimanjaro. It is based on the mineral silicate Zoisite but the blue/purple colour is thought to be due to trace amounts of V3+ ions replacing some of the Al3+ ions [3]. One of the intriguing properties of the gemstone is that it has a different colour when viewed from different directions under polarised light. It is also claimed that the colours becomes brighter after a high temperature heat treatment, but the cause of this is unknown. The student would measure low temperature single crystal polarised absorption spectra in the visible and near‐IR spectral range for the first time and the aim of the project is to interpret these unusual optical properties in term of the geometry of the VIIIO6 centres.
Luminescence and MCD of Egyptian Blue Egyptian Blue (CaCuSi4O10) is a pigment that was first synthesized some 3500 years ago. The pigment is ideal for non‐invasive investigation of archaeological artefacts as it shows an intense emission in the infra‐red [4]. The room temperature d‐d emission is very unusual for a copper (II) compound. The project will aim to understand the reason for this very efficient emission through time resolved fluorescence and low temperature magnetic circular dichroism (MCD) spectroscopic studies. [1] Saito et al, Phys. Rev. Lett., 2008, 101, 117402; [2] Saito et al, Nature Mat., 2009, 8, 634; [3] G. H. Faye, E.H. Nickel, Can. Mineral. 1971, 812; [4] G. Accorsi, et al., Chem. Commun., 2009, 3392.
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ASSOCIATE PROFESSOR JOE ROTHNAGEL Phone: 07 3365 4629 Email: [email protected]
Molecular Genetics, Cell Biology and Bioinformatics Gene expression in the skin Our research is focused on the molecular mechanisms that regulate skin and hair development and epidermal differentiation in order to provide the basic knowledge needed for improving the treatment of inherited and acquired skin disorders such as eczema, psoriasis, cancer and wounds. Importantly, the skin serves as an important model for other epithelia such as the gut, oral cavity, breast and prostate so lessons learned in these projects are broadly applicable to other tissues. We are looking for students with an interest in molecular biology, bioinformatics and genetics to investigate these areas and help us deliver new ways of treating skin and hair disorders.
Projects include:
• Post‐transcriptional regulation of skin genes • The role of Gli1 oncogene SNPs in the predisposition to skin cancers • Proteomic analysis of human skin
• Characterisation of sequence variants on 1q21 associated with hair phenotype
You don’t have enough genes buddy! After a decade of intensive study, the complete sequence of the human and other mammalian genomes has been determined. Amazingly, the estimate of the number protein‐coding genes in human is now thought to be less than 22,000. Yet most cells express a much higher number of distinct protein species. While some of this discrepancy can be accounted for by alternative transcription start sites, alternative splicing, mRNA editing and post‐translational modifications, we propose that our proteome is also derived from the translation of small open reading frames (sORFs) present in a variety of transcripts including the 5' untranslated regions (5'UTRs), 3’UTRs of many eukaryotic mRNAs and on non‐mRNA transcripts. These small peptides (sPEPs) may form the basis of a hitherto unknown regulatory network. These projects will involve a mix of bioinformatics, cell biology, and proteomics.
Projects include:
• Identification and characterisation of small proteins encoded by sORFs (with Ross Smith & Amanda Nouwens)
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DR SUSAN ROWLAND Phone: 07 3365 4615 Email: [email protected]
Getting the message – using the media to communicate science and the careers of scientists I am a teaching‐focused academic – as such my research interests revolve around teaching and learning. I am particularly interested in the use of print and radio/podcast media to help communicate the science message.
Free Energy Radio Free Energy Radio is an ongoing project where my students and I interview scientists and science graduates about their careers. There are several important questions to answer here. What are the qualities that make a scientist? What factors influence science career choices? How much real information do students actually have about science careers? What are the student responses to interviews with scientists? Can we define (and change) students’ conceptions of a career in science? Students working on this project will spend time in the JAC Radio studio talking with scientists and science students. They will analyse these interviews and the students’ responses to them. There is an opportunity to learn how to run the production software and edit audio interviews.
UQ SURJ SURJ@UQ is UQ’s new Science Undergraduate Research Journal; the first edition came out in 2012 and the second and third editions will appear in 2013 and 2014. The journal has a website: (https://shire.science.uq.edu.au/surj/) and Facebook site (facebook.com/SURJ.UQ).
I am the editor of this journal, which aims to help students develop their sense of professionalism as a scientist, while also increasing their ability to write in the popular science genre. This is particularly important, because the ability to write for specific genres is a major area of weakness in new science graduates. There are several questions we can answer here as well, most of which revolve around the development of student writing skills and students’ self‐authorship as science professionals and science communicators. You will have the opportunity to be involved in the production of UQ SURJ from the point of student submission, through editing and copy production, and finally production in hard‐copy as a UQ publication.
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PROFESSOR MARK SCHEMBRI Phone: 07 3365 3306 Email: [email protected]
The common research theme in my laboratory is the study of surface proteins that mediate adhesion, aggregation and biofilm formation by bacterial pathogens. Adhesion is the primary mechanism by which bacteria colonize host tissue surfaces and initiate disease. My research deals primarily with pathogenic Escherichia coli that cause intestinal and extra‐intestinal infections. A major focus is uropathogenic E. coli where we study the role of adhesins and other surface components in the development of biofilms and colonisation of the urinary tract. Biofilms are microbial communities characterized by cells that are irreversibly attached to a substratum or interface or to each other. Biofilms are of immense significance in medical, industrial and environmental settings and this area of study has enormous scope and importance in the field of bacterial pathogenesis. My laboratory also investigates mechanisms of adhesion and biofilm formation by other pathogens including Acinetobacter baumannii, Klebsiella pneumoniae and Enterobacter species.
Project 1: E. coli is the primary cause of urinary tract infection (UTI) in the developed world. It is estimated that one in four women and one in twenty men will develop a UTI in their lifetime. The aim of this project is to study the molecular characteristics of recently emerged multidrug resistant uropathogenic E. coli strains. The project will employ forefront molecular techniques including genome sequence analysis, proteomics, mutagenesis and cloning to characterise multidrug resistant strains and dissect their virulence capacity.
Project 2: Autotransporter proteins represent a major group of Gram‐negative bacterial secreted proteins that contribute to uropathogenic E. coli mediated UTI. Autotransporter proteins possess a range of virulence properties such as adherence, aggregation, invasion and biofilm formation. We recently characterised a novel translocation and assembly module that promotes efficient secretion of autotransporter proteins across the outer membrane and published this in collaboration with other research groups in Nature Structural & Molecular Biology. Recent genome sequencing of several uropathogenic E. coli strains has also identified a number of previously uncharacterised autotransporter proteins and we are currently trying to understand their contribution to virulence. This study aims to characterise some of these genes and their products, study their mode of translocation across the outer membrane and evaluate their role in adhesion, colonization and biofilm formation.
Project 3: Colonization of the bladder by uropathogenic E. coli results in the formation of intracellular cell aggregates encased in a polysaccharide‐rich matrix (ie. a biofilm). These structures enable the bacteria to cause chronic, persistent infections. Biofilm formation on medical implants such as catheters is also a major source of recurrent infection and resistance to antibiotics. This project will examine the role of several putative virulence factors (including uncharacterised fimbrial adhesins) from uropathogenic E. coli that are associated with biofilm formation.
Project 4: Klebsiella are frequent causes of nosocomial infections; it is estimated that they account for 8% of all hospital acquired infections in the western world. Next to E. coli infection, Klebsiella is the most common cause of Gram‐negative septicemia with a fatality rate of 25‐50%. In the majority of bacteremic cases, the focus of infection is the urinary tract. This project will identify and characterize novel virulence factors from Klebsiella pneumoniae.
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ASSOCIATE PROFESSOR GARY SCHENK Phone: 07 3365 4144 Email: [email protected]
Various Honours projects are available that focus on the study of metal‐ion containing biocatalysts (enzymes) and their application in drug design/development and bioremediation. Below the enzyme systems and relevant references are listed. The projects are part of a large collaborative network that includes several members of SCMB (Schenk, McGeary, Guddat, Gahan), and are funded by grants from the Australian Research Council (ARC) and the National Health & Medical Research Council (NHMRC).
Metallo‐β‐lactamases (MBLs) – a target to fight antibiotic resistance These enzymes require Zn2+ for their function and degrade and thus inactivate many of the commonly used β‐lactam‐based antibiotics (e.g. penicillin). They have emerged and evolved rapidly over the last couple of decades and hence pose a major problem for global health care since they are a major cause for the spread of antibiotic‐resistant pathogens. In this project the student(s) will investigate the properties of recently identified members of this class of enzymes and will design and synthesise potential inhibitors in an attempt to combat antibiotic resistance.
Pesticide‐degrading metallohydrolases – bioremediators of the future Organophosphate‐based pesticides have revolutionised agriculture since World War II. Unfortunately, the majority of these compounds are rather toxic to human health and their accumulation in the environment and gradual release into ground water leads to hundreds of thousands of poisoning cases (largely fatal) around the globe. Some soil‐dwelling bacteria have recently evolved enzymes that can break down these organophosphates into far less or non‐toxic molecules – these bacteria use pesticides as a source for phosphate for their metabolism. Hence, these enzymes have great potential as bioremediators. In this project students will investigate how these bioremediators work and how they can be optimised for applications in the environment (bioremediation).
Purple acid phosphatases (PAPs) – a new cure for osteoporosis? A “side‐effect” of our increasing life expectancy is that more and more people suffer from the bone disease osteoporosis. Osteoporosis is caused by increased resorption of bone, a process that is directly correlated with the expression of the enzyme PAP by osteoclasts (bone‐resorbing cells). Hence, PAP has become a major target in the design and development of new drugs against osteoporosis. In this project, students will design potential PAP inhibitors, assess their efficiency and investigate their interaction with the enzyme. References: [1] Mitić N., Smith S.J., Neves A., Guddat L.W., Gahan L.R. & Schenk G. Catalytic Mechanisms of Binuclear
Metallohydrolases, Chem. Rev. 2006, 106: 3338‐3363.
[2] Schenk G., Mitić N., Gahan L.R., Ollis D.L., McGeary R.P. & Guddat L.W. Binuclear metallohydrolases: complex
mechanistic strategies for a simple chemical reaction, Acc. Chem. Res. 2012, DOI: 10.1021/ar300067g.
[3] Schenk G., Mitić N., Hanson G.R. & Comba P. Purple Acid Phosphatase: A Journey into the Function and Mechanism of a Colourful Enzyme, Coord.Chem.Rev.2012,DOI:10.1016/j.ccr.2012.03.020.
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PROFESSOR ROSS SMITH Phone: 07 3365 4627 Email: [email protected]
Biochemistry and Molecular Cell Biology of hnRNPs
Much of our research centres on post‐transcriptional regulation of gene expression. One of our major interests is in the cell biology of RNA trafficking. Many mRNA molecules are targeted to discrete locations in cells as part of a mechanism for localising the proteins they encode. This is especially evident in oocytes and embryos where RNA localisation plays a major role in the establishment of cellular asymmetry and organismal development, but it is also important in mature somatic cells, including many brain cells. Our principal focus is on the molecular and cell biology of the heterogeneous nuclear ribonucleoprotein (hnRNP) A/B family of protein molecules. We have identified two highly abundant, largely nuclear proteins, hnRNPs A2 and A3, which bind RNAs bearing a special transport sequence (a "zipcode" called A2RE) in their 3'UTR. They are members of a group of multi‐tasking proteins, the hnRNPs, that are essential for the formation and trafficking of mRNA molecules in transport particles (“granules”). But there is more to it than that! In the nucleus they participate in such diverse processes as RNA packaging, telomere maintenance, alternative mRNA splicing, and RNA export. These proteins are truly multi‐functional and they play major roles in alternative splicing of pre‐mRNA, and the formation and maintenance of telomeres, two functions that are closely linked to cancer.
RNA Trafficking, Memory, and Mental Retardation (with Joe Rothnagel) Some mRNAs in neurons are packaged into granules, which are then transported along microtubules within dendrites to dendritic spines. When they are being transported these mRNAs are translationally suppressed: on reaching their destination they are activated, translating the protein they encode localized within the dendrites. Many of the proteins that are transported in this fashion are components of the post‐synaptic density and are thought to be involved in memory formation in the hippocampus. One component common to many granules is a protein called Fragile X mental retardation protein (FMRP), which regulates the other mRNAs that are present in trafficking granules and possess small elements that mark them for dendritic trafficking. Phosphorylation of FMRP results in activation of translation of the mRNAs encoding aCaMKII, Arc, NG, PKMz, MAP2, MAP1B and FMRP’s own mRNA. These proteins become components of the postsynaptic density in response to synaptic activation. The oncogenic protein, fyn, a tyrosine kinase, activates FMRP, A2 and other postsynaptic proteins, including TOG (Tumour over‐expressed gene). Of particular significance, the phosphorylation of FMRP activates ARC RNA and thereby mediates the endocytosis of AMPA receptors, which are needed for memory formation. Knocking out TOG in mice results in behavioural changes that mimic autism in humans. The principal aim in this project is to improve our understanding of the molecular mechanism of mRNA trafficking and the part it plays in mental retardation, Alzheimer’s Disease, and other mental conditions.
Telomeres and Cancer (with Joe Rothnagel) Telomeres are involved in the carcinogenic transformation of cells. They form structures in which repetitive dsDNA and ssDNA is used to cap the ends of chromosomes, enabling cells to undergo repeated division without loss of the remaining, non‐repetitive, genomic DNA. Tumour cells are distinguished from somatic cells by having comparatively long telomeres that are maintained primarily by the enzyme telomerase or, in some (ALT) cell types, by recombination pathways. Professor Elizabeth Blackburn (from Tasmania) shared a 2009 Nobel for her discovery of telomerase. hnRNPs associate with telomeric ssDNA and telomere‐associated proteins. They may regulate telomere length and cell proliferation, thereby playing a critical role in the growth of many cancers. We, and others, have demonstrated interactions between a subfamily of these proteins, the A/B hnRNPs, repeat telomeric ssDNA, and the RNA subunit of telomerase (hTR). The overarching hypothesis in this project is that the A/B hnRNP protein family has a major role in telomere maintenance and hence in carcinogenesis. We wish to describe, at the molecular level, the mechanism that allows tumour cells to maintain telomere length and avoid entering senescence, and the roles played by the hnRNPs in this process.
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DR KATE STACEY Phone: 07 3346 2072 Email: [email protected]
Recognition of Cytosolic DNA as a Danger Signal
The DNA of eukaryotic cells is contained within a membrane‐bound nucleus, and the appearance of DNA within the cytosol indicates a danger to the cell. Cytosolic DNA can result from viral and bacterial infections or the activity of endogenous retroviruses within the human genome. Responses to cytosolic DNA include production of the anti‐viral protein interferon‐�, and cell death. We identified AIM2 as a receptor for cytoplasmic DNA eliciting cell death. AIM2 initiates formation of an “inflammasome” which is a protein complex leading to activation of the protease caspase‐1 and lytic cell death. We have recently shown that AIM2 recognition of DNA also recruits and activates caspase‐8, which leads to the death of cells by apoptosis. Although the AIM2 pathway is only found in mammals, we find that chicken and insect cells can also die after introduction of DNA into the cytosol. Consequently we propose that defences against invading DNA are essential for defending against infections and guarding the genome of all multicellular organisms.
Future studies will focus on:‐ 1) Characterisation of the role of DNA detection in combatting viral infections 2) Definition of pathways of recognition of foreign DNA in non‐mammals 3) Characterisation of the inflammasome complex induced by AIM2, and novel death‐domain interactions
involved in recruitment of procaspase‐8 4) Investigation of the role of AIM2 (absent in melanoma 2) as a tumour suppressor
Inflammasome Deficiency in Autoimmune Disease The human autoimmune disease lupus involves formation of antibodies against self molecules and their deposition as immune complexes in tissues. Inflammasomes lead not only to cell death but also to release of the inflammatory cytokine IL‐1b. Although most researchers have assumed that inflammasome pathways will be elevated in autoimmunity, we find the opposite; in a mouse model of lupus there is profound deficiency of three different types of inflammasome structures. We propose this leads to an altered response to commensal organisms and poor clearance of pathogens, and promotes autoimmunity. Projects will include:
1) Establishing the molecular basis for inflammasome deficiency in the mouse 2) Investigating whether human lupus patients have inflammasome deficiency Relevant Publication: Roberts, T.L., Idris, A., Dunn, J.A., Kelly, G.M., Burnton, C.M., Hodgson, S., Hardy, L.L., Garceau, V., Sweet, M.J., Ross, I.L., Hume, D.A., Stacey, K.J. (2009) HIN‐200 proteins regulate caspase activation in response to foreign cytoplasmic DNA. Science 323:1057‐1060.
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PROFESSOR ISTVAN TOTH Phone: 07 3346 9892 Email: [email protected] Website: http://staff.scmb.uq.edu.au/staff/istvan‐toth
Oral delivery for next generation vaccines Vaccination is one of the most effective public health strategies ever undertaken. Instead of whole killed pathogens, next generation vaccines use pathogen‐derived peptides, allowing fine control when tailoring the vaccine. This project aims to employ a novel carrier system using lipoamino acids (LAA) to vaccines that can be delivered orally. Preliminary experiments with a limited number of LAA have demonstrated their ability to form vesicles alone or in the presence of cholesterol (unpublished observations) that can act as oral antigens. It is anticipated that vesicle size, stability, drug loading, permeability, lipophilicity, antigenicity, in vivo behaviour, etc. will depend on the LAA composition of the liposomes. Project aims: to extend the existing liposomal technology by developing novel vesicular drug delivery systems in which vaccine, adjuvant, and particulate carrier are contained in a single molecular entity.
A Novel System for Peptide Delivery Drugs with poor oral absorption profiles can be delivered in a stable form when conjugated to a carrier. Our lipoamino acid (LAA) or lipopeptide (LP) based carrier systems have been used to improve the systemic bioavailability of anti‐inflammatory alkaloids, analgesics, GABA, antimicrobials, and several anti‐cancer agents. This project aims to apply the existing carrier system to the delivery of LHRH, a 10 amino acid long peptide hormone. Project aims: 1) the chemical synthesis of LAA libraries and a series of delivery system‐LHRH conjugates with different linkages, 2) in vitro biological stability studies, 3) uptake studies, and 4) biological activity assessment.
Gene Delivery Systems Gene delivery technology is limited by poor absorption/uptake, tissue targeting, gene release after uptake, and rapid enzymatic breakdown. This project will address these major issues through a novel strategy involving ion pair formation of lipophilic dendrimer constructs with an antisense oligonucleotide sequence (ODN). An established animal model of chorroidal neovascularisation (CNV) will be used to test the new dendrimer/ODN1 complexes. Project aims: 1) Produce new dendrimer‐oligonucleotide (ODN1) complexes. 2) Test the biological stability and permeability of these dendrimer complexes. 3) Determine the optimal ratio of the delivery system and the antisense DNA using isothermal micro‐calorimetry. 4) Test the uptake and biological activity of dendrimer complexes in retinal cells, and select the most effective complex for in vivo studies.
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PROFESSOR MARK WALKER Phone: 07 3346 1623 Email: [email protected]
My lab focuses on the mechanism by which the group A streptococcus (Streptococcus pyogenes; GAS) causes invasive disease and GAS vaccine development. S. pyogenes is the etiologic agent of numerous suppurative diseases, ranging from mild skin infections such as pharyngitis, scarlet fever, impetigo and cellulitis, to severe invasive diseases such as septicemia, streptococcal toxic shock syndrome and necrotizing fasciitis. GAS is placed within the "top 10" infectious disease causes of human deaths worldwide. Indigenous Australians suffer the highest rates of affliction with GAS diseases in the World. Of the over 100 M serotypes, the M1T1 clone that emerged in the mid‐1980s and disseminated globally, causes most deaths and morbidity. Our research projects are undertaken on a collaborative basis with colleagues at the University of Queensland, QIMR, UTS, Griffith U., U. Adelaide, Notre Dame U., German National Centre for Biotechnology, U. Cambridge, U. Cincinatti and UCSD.
Research projects: (1) Role of bacteriophage in GAS evolution: Recent genomic and pathogenesis studies have implicated bacteriophage determinants as important contributors to GAS virulence. In this project, we will use genomics to characterize the steps involved in GAS evolution and investigate the contribution of phage virulence determinants to the disease process. (2) The mechanism of GAS invasive disease initiation and the role of human plasminogen as a GAS virulence determinant: Recent investigations have highlighted the hijacking of human protease plasmin by GAS, which contributes to dissemination and invasive disease. This project will continue our efforts to elucidate the mechanism by which GAS cause invasive infections. (3) The interaction of GAS with human epithelial cells and innate immunity: We have begun the task of detailed charcterisation of the interaction of GAS with the host epithelial surface and innate immune defense mechanisms. This project will examine the role of host and pathogen factors in the colonization, establishment and clearance of GAS in the human host. (4) GAS antigen identification and vaccine development: A safe and efficacious commercial GAS vaccine has yet to be developed. In this project, we are characterizing new surface proteins and examining their potential as GAS vaccine candidates. Group research staff (involved in honours student support): NHMRC overseas training Fellows: Jason Cole, Mark Davies, Andrew Hollands; Postdoctoral Fellows: Tim Barnett, Amanda Cork, Christine Gillen, Cheryl Ong.
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DR JACK WANG
Phone: 07 3346 9490 Email: [email protected]
Research into Science Education I am a Teaching‐focused academic in Microbiology, and my research revolves around innovative teaching and learning strategies in Science Education. This type of research is not associated with extensive laboratory work, and therefore will not prepare you for a career as a laboratory scientist. It instead relies upon interacting with large networks of people – namely the students, academics, and administrators in Higher Education – to extract trends and patterns in their ideas regarding teaching and learning. You will gain experience in designing and analysing surveys, conducting focus group interviews, preparing video and multimedia content, interpreting both quantitative and qualitative data, and communicating with a diverse range of stakeholders in Science Education. These projects may be useful for you if you are interested in careers in educational development and learning design in both public and private sectors:
1. Mapping active‐learning strategies across large undergraduate science classes Teaching and learning science within the large undergraduate classroom can be daunting for students and academics alike. Complex scientific concepts are conveyed to hundreds of students at the same time, and it can be difficult to engage the cohort’s interest and attention throughout the semester. This project will aim to produce a set of case‐study‐driven guidelines for instructors teaching into large undergraduate science courses. It will build from existing best‐practice guidelines for effective active‐learning strategies, and continue to document and evaluate examples of engaging in‐class activities used in large science courses across Queensland universities. You will attend a variety of large science classes, collate and interpret teaching evaluation scores, and survey and interview large numbers of students and academics in order to determine and evaluate the effectiveness of active‐learning within each educational context.
2. Measuring the impact of authentic research experiences throughout Science Education In order to better prepare students for a career in scientific research, authentic research experiences have been increasingly embedded across all levels of undergraduate science programs. This project aims to evaluate the cumulative impact of these experiences on students interested in scientific research careers. The project methodology will involve surveying and interviewing students at different stages of their research training, and attempt to correlate their confidence and competence in key research skills to their previous experiences in authentic research. Using this data, we will aim to establish which types of exposure to authentic research best prepare students for future research training in the sciences, as well as how research higher degree students can be better supported in their studies. Key references: Wang, J.T.H. et al., (2013). How much is too much assessment? Insight into Assessment‐driven student learning gains in large‐scale undergraduate microbiology courses. Journal of Microbiology and Biology Education, 14(1): 12‐24. (http://jmbe.asm.org/index.php/jmbe/article/view/449) Wang, J.T.H. et al., (2012). Immersing undergraduate students in the research experience. Biochemistry and Molecular Biology Education 40(1): 37‐45 (http://onlinelibrary.wiley.com/doi/10.1002/bmb.20572/abstract)
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ASSOCIATE PROFESSOR LEIGH WARD Phone: 07 3365 4633 Email: [email protected]
Medical and Metabolic Biochemistry Honours projects which are available in the above areas are as follows:
Nutritional Biochemistry – Omega 3 fatty acids and cardioprotection This project is in association with Prof Lindsay Brown University of Southern Queensland. This project will require the student to work periodically at USQ, Toowoomba. Our recent studies have characterised the cardiovascular changes in high fat, high carbohydrate diet‐ induced obesity in rats, showing that these changes can be prevented or reversed by dietary interventions such as olive leaf extract and omega‐3 fatty acid (α‐linolenic acid)‐rich chia seed supplementation. This project will extend these studies to determine the possible beneficial cardiovascular responses following addition of omega‐3 fatty acids from other sources including deep sea algae (docosahexaenoic acid (DHA)‐rich), fish oil (eicosapentaenoic acid (EPA)‐rich) and flax seed (alternate source of α‐linolenic acid) to this diet, together with fat redistribution. See Poudyal H et al. (2012) Chronic high‐carbohydrate, high‐fat feeding in rats induces reversible metabolic, cardiovascular, and liver changes. Am J Physiol Endocrinol Metab. 302: E1472‐1482.
Medical technology – Development of bioelectrical impedance technology for the early detection of
lymphoedema Bioelectrical impedance analysis is a non‐invasive technique for the measurement of the electrical properties of the tissues and the whole body that may be related to its composition. One application is the assessment of fluid accumulation in tissues that occurs in breast cancer‐related lymphoedema. This project will continue development of an impedance probe for the detection and quantification of lymphoedema. It will aim to validate this novel technology against other assessment tools such as MRI, pQCT and DXA. See Ward LC, et al. (2008) Bioelectrical impedance analysis for early detection of lymphoedema. In Lymphedema Diagnosis and Therapy Eds H. Weissleder and C Schuchhardt, Chap 15. p 502‐517, Viavital Verlag Gmbh Publ., Essen.
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DR NICK WEST Phone: 07 3365 4093 Email: [email protected]
Tuberculosis Mycobacterium tuberculosis is the single most important bacterial pathogen of humans, killing approximately 4,000 people each day. Despite a concerted international effort to reduce the global health burden of TB, more people than ever before, with approx. 1 in 3, are infected with M. tuberculosis. TB is a highly contagious, disease transmitted by inhalation of aerosol droplets generated from an infected individual. TB was declared a world health emergency in 1993 and remains so today.
“The spread of drug resistant TB threatens to destabilise the global initiatives of TB control. More effective anti‐TB drugs are urgently needed”
Our research is centered on the bacterium and the mechanisms it employs to cause disease. Over the past few years we have been defining the genetic repertoire required by the bacterium to colonise the host, spread around the body and to persist in a state of latency. We have compiled a valuable list of essential genes utilized for these processes from which we can now begin to identify potential new drug targets.
Two projects will be offered in the laboratory in 2013:
1. Essential gene regulation in mycobacteria. Our genetic screening identified a series of transcriptional regulators essential to survival of the bacterium in vivo. In this project you will clone, express and purify two novel regulators. Mutants of these genes will be produced in Mycobacterium smegmatis, and avirulent fast growing mycobacteria. In order to define the role of these regulators the influence of these mutations will be assessed by transcriptomic analysis. The DNA binding sites will be determined and a preliminary inhibitory drug screen conducted. Skills and Techniques: Various microbiological techniques, PCR and molecular analysis. Gene cloning and proteomics. DNA binding assays and small molecule inhibition, macrophage cell culture and mycobacterial infection may also be performed.
2. Characterisation of proteins essential for survival in the host. We have identified a series of bacterial factors which are dispensable for growth in laboratory media but which are in‐dispensable in the host. This project will define the role of three of these essential virulence determinants by modern molecular and proteomic approaches. Additionally these proteins will be trialed as vaccine candidates, establishing their Immunogenicity and protective efficacy. Skills and Techniques: Various microbiological techniques. Gene cloning and site directed mutagenesis. Protein and/or DNA vaccinations. Immunological assays including ELIspot and ELISA. Macrophage cell culture and mycobacterial infection.
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ASSOCIATE PROFESSOR CRAIG WILLIAMS Phone: 07 3365 3530 Email: [email protected]
Natural product total synthesis, isolation and associated medicinal chemistry.
Drug Design and Development
Green chemistry
Anti‐cancer, neurodegenerative disease and insect active limonoids: [in collaboration with Dr Paul Savage (CSIRO), Prof. Peter Dodd (SCMB. UQ) and A/Prof. Gimme Walter (SBS, UQ)]. Recently we achieved the total syntheses of a number of the limonoid family members, such as, Khayasin 1 and Cipadonoid B 2. The synthesised limonoids 1 and 2 are closely related to Gedunin 3, another limonoid family member, which displays anti‐cancer and neurodegenerative disease activity in Heat Shock protein 90 (Hsp90) models. We would now like to investigate the total synthesis of gedunin 3, which has yet to be reported, and explore the gedunin 3 structure against Hsp90 using state of the art medicinal chemistry techniques.
Cubane Chemistry: A Benzene Ring Drug Isostere? [in collaboration with Dr Paul Savage (CSIRO) and Prof. James De Voss (SCMB, UQ)]. Cubane 4, when viewed from the corners (i.e. 5) can be considered roughly the same size as a benzene ring (i.e. 6). This is equally true when you take into consideration the � clouds of benzene, that is, cubane 4 is about the same "thickness". Therefore the 1,2‐ 1,3‐ and 1,4‐ substituted cubanes are similar to ortho‐, meta‐, and para‐substituted benzenes respectively. Furthermore, the cubane structure is actually very stable – cubane ring‐opening is thermally disallowed by orbital symmetry. With this in mind the project would involve replacing the phenyl ring in a current drug molecule and comparing bioloical assay data. It would also be expected that cubane 4 has completely different P450 metabolism profiles, which will be explored in collaboration with Prof. James De Voss.
Discovery and Development of Novel Analgesics [in collaboration with Prof. Maree Smith from the Centre for Integrated Preclinical Drug Development (CIPDD)/TetraQ)]: The prevalence of painful diabetic neuropathy (PDN) is 7% within a year of diagnosis of diabetes and 50% by 25 yrs of diabetes. The medicines currently used to treat PDN are not effective in less than 50% of patients. Hence, we propose to develop new, effective medicines for the alleviation of PDN by investigating the biology (Smith lab) of unusual heterocycles (Williams lab) that deliver the neurotransmitter molecule NO (nitric oxide).
Green Chemistry [in collaboration with Prof. Ian Gentle (SCMB, UQ)]. Organic reactions are key to new molecules that are in ever‐increasing demand for applications in the pharmaceutical, materials and agrichemical sectors. This demand, however, places growing pressure on synthetic chemists to limit or even eradicate environmentally unfriendly chemical waste production. Steps towards such measures are now commonly termed "Green Chemistry". Projects looking at developing new solvents and new surfactants are available. Applying physical techniques [e.g. small angle scattering (SAXS), neutron scattering (SANS) and dynamic light scattering (DLS)] to understand macromolecular mechanisms is an important part of the work.
A/Prof. Williams (ARC Future Fellow) he has held past and present multimillion dollar industry research contracts in addition to ARC and NHMRC grants. Further projects are available on request.
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DR SIMON WORRALL Phone: 07 3365 4626 Email: [email protected]
Mechanisms of Drug‐Induced Tissue Injury Liver, muscle, heart and brain injury have long been associated with the abuse and clinical use of drugs. My research interests focus on ethanol, perhaps the most commonly abused drug. Ethanol is widely tolerated but induces tissue injury in a small number of individuals. The potential research projects listed below will investigate immunological and genetic phenomena associated with alcohol‐induced tissue injury.
The potential projects available are: 1. Studies on the aetiology of ethanol‐ induced tissue injury to liver, skeletal and cardiac muscle, and
brain? 2. Is protein modification by ethanol metabolites involved in the aetiology of:
a. Alcoholic liver disease? b. Alcoholic skeletal and cardiac myopathy? c. Alcoholic brain injury (with Peter Dodd)?
3. Novel protein modifications induced by ethanol metabolism (with Craig Williams, chemistry) 4. Discovery of molecular markers for the severity of Alzheimer’s disease.
A reaction
scheme showing
the formation of
malondialdehyde
‐acetaldehyde
dd t
Expression of GFP‐tagged human keratin 18 in a primary rat hepatocyte.
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PROFESSOR PAUL YOUNG Phone: 07 3365 4646 Email: [email protected]
VIROLOGY UNIT
Antiviral Targets of Dengue and West Nile Viruses We have been investigating three separate proteins that are encoded by dengue and West Nile viruses as targets for antiviral drug design. These are the virion surface protein E, which mediates viral fusion with the cellular membrane, the viral protease NS3, whose activity is crucial to the cleavage of the viral polyprotein precursor and NS1, a key player in viral RNA replication. In order to gain a clearer understanding of the molecular basis of the key functional activities of these proteins, a series of projects are available that use site‐directed mutagenesis of recombinant proteins as one approach to investigate the role that specific residues and domains in these proteins may play in their respective activities.
Koala Retrovirus as a Model for Cancer Induction We have recently identified a direct association between high blood levels of a retrovirus of koalas and the incidence of cancer in this iconic species. Furthermore, we have shown that this virus is an endogenous element in the koala genome. Projects are available that will investigate the location of the retroviral insertions in the koala genome, the methylation status of these insertions and their transcriptional activation.
Constrained Alpha Helical Peptidomimetics as Inhibitors of Viral Fusion Respiratory syncytial virus is the most important respiratory pathogen of young children, however there are few disease control options currently available. We have identified a key domain within the RSV F protein that appears to play a pivotal role in the process of viral fusion with the outer cell membrane. This domain comprises part of an extended amphipathic alpha helix. In collaboration with Professor David Fairlie of the IMB we are investigating the possibly of structurally constraining short peptide mimics of this domain and testing their potential as inhibitors of fusion activity. This project will entail peptide synthesis, recombinant protein expression and cell culture based studies.
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PROFESSOR DEBRA BERNHARDT SCMB and AIBN Group Leader Phone: 07 3346 3939 Email: [email protected] Website: www.aibn.uq.edu.au/debra‐bernhardt
My group research group is interested in the study of matter using theoretical and computational methods that can ultimately be used to address a wide range of practical problems. Applications of interest include transport in nanopores, fluctuations in nanoscale systems, melting, solubility, separation of gases, lubrication, design of ionic liquids, design and assessment of materials for energy conversion and storage, carbon dioxide sequestration and catalysis. Our group has world leading expertise in various theoretical and computational methods ranging from quantum chemical calculations to the statistical mechanics of nonequilibrium systems, access to high performance computing facilities and an international team of collaborators.
Possible projects include:
Transport in nanoporous systems Nanoporous solids are used as adsorbents in pollution control, industrial separations, storage of fluids and catalysis. Simulations can be used to assist in the design of better materials, and to understand the fundamental nature of the adsorption and transport processes. One of the key factors determining flow of fluids through nanopores is their stick or slip behaviour near the walls. We have recently developed a new approach for studying this behaviour that should be more efficient for complex systems.
Computational studies of ionic liquids Ionic liquids have exceptional solvation properties and electrical conductivity, meaning they have a wide range of industrial applications. By combining different ions, ionic liquids can be designed to optimize their properties. However, the science of ionic liquids is new and therefore prediction of their properties is problematic. To address this, we are taking advantage of recent developments in nonequilibrium statistical mechanics to create efficient algorithms to determine key properties of ionic liquids.
Statistical mechanics of nonequilibrium fluids Any system that is flowing, stirred, has a temperature gradient across it or is subject to an external field is in a nonequilibrium state. The properties of these systems are not well developed when the systems are far from equilibrium. In this project theory and computational methods will be used to expand our fundamental understanding of these systems.
Quantum mechanics for the design of new materials New materials are required for solar energy applications, catalysis, adsorbents for pollutants, storage of fuels, new polymers, fuel cells etc. Quantum mechanics enables the properties of these materials to be predicted in an efficient and cost effective manner. Projects are available that will focus on the prediction of material properties using a range of computational quantum chemical methods.
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DR GRAHAM LEGGATT Phone: 07 3176 5937 Email: [email protected]
My laboratory studies the immune response to non‐melanoma skin cancers.
Projects include:
(1) T cell‐‐‐based immunotherapy of skin cancer after lymphodepletion. (2) The role of IFN‐‐‐g in suppressing immune responses to skin precancers. (3) Mechanisms of lymphocyte trafficking to skin precancers.
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PROFESSOR MICHAEL MONTEIRO Phone: 07 3346 6164 Email: [email protected]
Living Polymers Polymers made by living radical polymerization have well‐defined chain length and architecture. The structures that can be synthesised are block, star, branched, gradient and even dendrimer. The advantage of such a technique is the wide range of functional monomers that can be incorporated in these architectures, allowing materials from biomedical applications to coatings to electronic devices to be prepared.
Nanostructures for Drug Delivery The aim of the project is to synthesis the next generation of nanostructures built from linear polymer chains. The project will attempt to make a wide range of architectures that are currently unavailable and in collaboration with Cell Biologists use these as vehicles for drug and vaccine delivery devices. (ARC Dicovery granted 2009)
‘Smart’ Nanoreactors for Environmentally Friendly Organic and Polymer Reactions Nanoreactors provide the ideal setting where selected chemical reactions can take place with high efficiency in controlled environments. The aim of this project is to use these ‘smart’ nanoreactors in the synthesis of molecules and macromolecules with high chemical selectivity and rapidly. This opens a method for the synthesis of new compounds and polymers previously unaccessibly. (ARC Dicovery granted 2009)
Smart Nanostructures for Drug Delivery The aim of this project is to synthesis polymers with complex architectures on the nanoscale in an environmentally friendly medium, water. Once these well‐defined nanostructures have been made their structure‐property relationship will be evaluated using structural characterization techniques such as electron microscopy for size and morphology, and will be functionalised for use as drug and gene delivery devices.
Nanopolymer Composites Prepared in Water The aim of this project is to synthesis polymers with complex architectures (as shown above) on the nanoscale in an environmentally friendly medium, water. The synthesis will involve using a wide range of Living radical polymerizations towards a deeper mechanistic understanding of the reaction pathways. Once these well‐defined nanostructures have been made their structure‐property relationship will be evaluated using structural characterization techniques such as electron microscopy for size and morphology, and will be functionalised for use as drug and gene delivery devices.
Mechanisms in Living Radical Polymerization Understanding the mechanisms in living radical polymerization allows for better design of the living agents and the optimal use of living polymerizations. The project will involve the determination of the initiation mechanisms involved in Atom Radical Transfer and Reversible Addition‐Fragmentation chain Transfer polymerizations. This will enable us to determine the dominant mechanisms and what factors control addition, fragmentation and transfer reactions for these living processes.
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PROFESSOR MATT TRAU Deputy Director (AIBN) Phone: 07 3346 4173 Email: [email protected] Website: www.aibn.uq.edu.au/matt‐trau
Our Centre for Biomarker Research and Development is located in the Australian Institute for Bioengineering and Nanotechnology (AIBN) and has access to state‐of‐the‐art chemistry synthesis, and characterisation facilities. Students working in the Centre will have the opportunity to create nanoscaled biosensors for applications in cancer, infectious disease and point‐of‐care devices. Students will also be given the opportunity to work with leading geneticists, epigeneticists and clinical researchers to test these devices in clinical settings. The Centre has a focus on developing diagnostic devices for early detection of diseases such as cancer, when it is most responsive to treatment which also provides the greatest social and economic benefits to society. Nanotechnology offers the promise of miniaturized, inexpensive, flexible and robust “plug‐and‐play” molecular reading systems which can be effectively deployed to detect diseases in a clinical setting. Current projects available include:
1) Microfluidic Devices for Capturing Rare Circulating Tumour Cells The progression of cancer in patients is characterized by cells that invade locally and travel through the blood stream to metastasize in the other parts of the body. These cells, account for 1 or fewer cells in 106 blood cells and are known as circulating tumour cells (CTCs). Development of advanced technologies for capturing CTCs in blood in the early stage of the metastasis process would transform the treatment of cancer. This project strives to build and test a microfluidic device to enable selective capture and detection of CTCs using three‐dimensional microstructured electrodes within the device.
2) Nanodevices/Nanobiosensors for Cancer Biomarker Proteins Detecting low concentrations biomarkers in serum is potentially useful for the diagnosis and prognosis of a disease. The development of a detection method that is rapid and cheap could revolutionize the treatment of diseases such as cancer. In this project, we aim to fabricate nanobiosensors with nanostructured 3D‐electrodes to detect single protein molecules in blood. Students will achieve hands on experience in the design, fabrication and application of the microfluidic devices and electrochemical micro(nano)biosensors.
3) DNA Nanomachinery for Early Breast Cancer Detection Subsets of non‐coding (nc) RNAs serve as potential biomarkers of diseases. This project involves designing, developing and evaluating novel DNA nanomachinery to perform tasks that are currently beyond the reach of existing molecular readout technologies. We aim to use these nanomachines as a new technology platform to rapidly detect ncRNA biomarkers in breast cancer patients. This interdisciplinary project will provide an opportunity for students to acquire diverse skills in chemistry, molecular biology and bioengineering.
4) Point‐of‐Care Diagnostics Point‐of‐care (POC) diagnostics have the potential to revolutionise global health care by enabling diseases to be rapidly diagnosed ‘on the spot’ using minimal specialised infrastructure. POC devices need to be highly sensitive, specific, practical, cost effective and portable if they are to be used in resource limited settings. We are focused on novel and simple molecular assays to generate new POC diagnostic technologies. Students will be involved in designing, developing and evaluating methods to rapidly detect pathogenic DNA using devices such as mobile telephones. This interdisciplinary project will provide an opportunity to acquire diverse skills in chemistry, molecular biology, bioengineering, and biotechnology.
SCMB RESEARCH FELLOWS
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DR ELIZABETH KRENSKE ARC Future Fellow
Phone: 07 3365 4632 Email: [email protected]
Computational Explorations of Organic Reactivity
We use advanced computational techniques to investigate aspects of molecular reactivity that are invisible to the experimentalist. Quantum mechanical calculations (e.g. DFT) are applied to explore the mechanisms of newly‐discovered synthetic transformations, to explain how stereocontrol is achieved, and to design new reactions. We are especially active in discovering previously‐unknown mechanisms of stereocontrol involving non‐covalent interactions.
Honours projects in this laboratory involve collaborations with leading synthetic chemists both in Australia and internationally, and will equip the student with modelling skills that should prove equally advantageous either as a complement to further research in synthetic chemistry or as an entry point to advanced theoretical research.
DR MEGAN O’MARA
Phone: 07 3365 7562 Email: [email protected]
Investigating membrane transport using molecular dynamics simulation techniques
Regulation and control of membrane transport is an integral part of normal cell function, from nutrient uptake to signalling and removal of metabolic by‐products. The ABC multidrug transporter, P‐glycoprotein, exports over 120 distinct drugs, chemotherapeutic agents and endogenous substrates. It is well established that the expression of P‐glycoprotein in cancer lines is a major cause of chemotherapy resistance, however the molecular details of drug uptake and transport by P‐glycoprotein remain unclear. Recent investigations have also demonstrated that platelet‐activating factor (PAF), a potent phospholipid activator of leukocyte‐induced inflammation; and amyloid‐� peptide (A‐� peptide), the major component of amyloid plaques in Alzheimer’s disease, are two endogenous transport substrates of P‐glycoprotein. These results suggest that the transport activity of P‐glycoprotein may play a role in initiating both inflammatory processes and Alzheimer’s disease, as
well as in the development of chemotherapy resistant cancers.
The aim of this project is to understand the molecular details of both endogenous and drug substrate interactions with P‐glycoprotein and the cell membrane, using computational tools such as molecular dynamics simulations and free energy calculations.
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DR BENJAMIN SCHULZ Phone: 07 3365 4875 Email: [email protected]
Molecular Systems Glycobiology
My research focuses on the mechanisms and biological roles of protein glycosylation.
Project 1: Drug resistance and N‐glycosylation in breast cancer Docetaxel is an important chemotherapeutic drug for treatment of breast cancer, although tumours can develop resistance. This study seeks to understand how protein glycosylation allow tumours to become resistant to docetaxel. This project will use cell culture, mass spectrometry proteomics and bioinformatics.
Project 2: Engineering glycoproteins for improved expression Many proteins currently used as pharmaceuticals or in biotechnology are glycoproteins, such as erythropoietin (EPO) and monoclonal antibodies. This project will further develop a low‐cost bacterial expression systems. using site‐directed mutagenesis, protein expression, purification and characterization.
Project 3: Evolvability and robustness of protein glycosylation N‐glycosylation of proteins helps them to fold correctly, and is also important in regulating the activities of mature glycoproteins and is catalyzed by an enzyme called OTase. This project will experimentally model this co‐evolution by mutating the accessory proteins of OTase and quantifying the effect of these mutations on protein glycosylation at a systems level.
DR ANNETTE SHEWAN Phone: 07 3365 4634 Email: [email protected]
Epithelial Morphogenesis and Cancer Cell Biology
Understanding the mechanistic basis of epithelial morphogenesis is a major challenge in modern biology, with clear ramifications for human health and disease. The formation of a tissue requires timely and well‐orchestrated interactions of different cells within their microenvironment. These cellular interactions underpin developmental processes and support normal tissue form and function. Crucial to normal epithelial tissue function is the establishment of cellular polarity. Epithelial tumours can arise as a result of loss of polarity and it is becoming increasing apparent that the interaction of transformed cells with their microenvironment is instrumental in tumour growth and metastasis. My program is focussed on unravelling the molecular mechanisms that underpin the establishment and maintenance of cellular polarity. The over‐arching goal is to build a comprehensive understanding of how disruption of cellular polarity contributes to cellular transformation, which ultimately results in cancer cell dissemination and tumour progression.
Research Projects available in the following areas: ‐ Molecular mechanisms of epithelial polarity and cellular transformation. ‐ Polarity protein control of plasma membrane asymmetry: establishing the fence. ‐ Protein trafficking in cell polarity. ‐ Molecular regulation of tissue growth by polarity protein networks. Techniques Employed: Mammalian cell culture (2‐D & 3‐D), DNA cloning and mutagenesis, QRT‐PCR, miRNA assays, cellular signalling, protein‐protein interactions, RNAi techniques, transformation assays, epi‐fluorescence and confocal microscopy.
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DR PAVLA SIMERSKA Phone: 073365 4636 Email: [email protected]
Enzymatic ligation methods for drug and vaccine delivery The aim of this project is to develop efficient enzymatic ligation techniques for the synthesis of drug and vaccine therapeutics. Many peptides have been identified as potential new medicines but only a few have progressed into clinic mainly due to their rapid enzymatic breakdown, problematic delivery and/or their poor inherent immunogenicity. This project will address the major issues in peptide delivery through a strategy involving environmentally friendly enzymatic transformations for coupling of sugars and/or lipids to the therapeutic peptides of interest. These peptide modifications are designed to improve peptide absorption, metabolic stability, and concentration of peptides at their active sites by utilizing carbohydrate and/or amino acid transport systems. The application of the enzymatic synthesis provides access to complex carbohydrate structures that can by used to target carbohydrate receptors such as asialoglycoprotein. Available projects include development of enzymatic peptide ligations for synthesis of group A streptococcal vaccine candidates using glycosidases and peptidases and enzymatic glycosylations of pain regulating peptides for CNS delivery using glycosyltransferases.
DR MARIUSZ SKWARCZYNSKI Phone: 07 3346 9894 Email: [email protected]
Nanovaccines Recent developments in nanomedicine/vaccinology have found that the size and morphological characteristics of nanoparticle vaccines affect their efficacy. Preliminary investigations have demonstrated that 20 nm polymer‐based nanoparticles that displayed peptide epitopes on their surface were able to induce very strong immune responses against those epitopes. We have also shown that this response was size dependent. This project aims to further explore the effect of size and morphology on the efficacy of nanoparticle vaccines. Project aims: 1) Produce polymer‐peptide chimeras that possess the desired epitope. 2) Establish reproducible self‐assembly method to synthesise the construct into nanoparticles. 3) Produce and self‐assemble multi‐epitope vaccine constructs. 4) Fully characterise nanoparticles including the surface arrangement of the epitopes.
Peptides
Peptide therapeutics
Enzyme
Glycosylation
Lipidation
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DR MAKRINA TOTSIKA
Phone: 07 3365 3830 Email: [email protected]
My research focuses on the molecular mechanisms employed by pathogenic bacteria during infection of the host. Current projects include: 1. The multidrug resistant Escherichia coli pandemic: how molecular insight into bacterial pathogenesis can lead to novel therapies E. coli sequence type 131 is a ‘high‐risk’ group of multidrug resistant pathogens that emerged recently and spread rapidly worldwide. The pathogenic success of E. coli ST131 is not fully understood. Using relevant cell and animal infection models combined with bacterial genomics and genetic engineering, we unravelled unique aspects of E. coli ST131 pathogenesis and identified novel adhesion inhibitors that prevented and treated chronic bladder infection with E. coli ST131 in mice. Students working in this project will gain strong experience in bacterial genetics and molecular biology techniques, working with bacterial genomes and using cell and animal infection models to enhance our understanding of E. coli ST131 pathogenesis, and address the urgent and currently unmet need for novel alternatives to antimicrobial treatment of UTI that are refractory to antibiotics. 2. Understanding how bacteria become sticky Bacteria produce sticky fibers, termed adhesins, which mediate bacterial attachment to biotic or abiotic surfaces (e.g. host cells or catheters) and are essential for colonisation of their ecological niche. Gram‐negative bacteria express a large repertoire of adhesins, including fimbrial and autotransporter (AT) adhesins. Although adhesin assembly has been studied extensively, recent findings implicate periplasmic enzymes in the early assembly steps. We use uropathogenic E. coli (UPEC) as a Gram‐negative model organism to dissect the contribution of different periplasmic proteins in the assembly of fimbrial and AT adhesins. Students working in this project will use genetics, molecular and cellular microbiology, biochemistry and proteomics to advance our understanding of how bacteria produce adherence factors that aid in host colonization. This can help identify novel targets for anti‐virulence approaches as alternative infection therapeutics.
DR GEORGE VAMVOUNIS
Phone: 07 3366 7989 Email: [email protected]
Photoswitchable Plastic Electronics Organic photochromic molecules reversibly change colour with light, i.e. photoswitch, as shown in Figure 1.
Figure 1: A typical photochromic molecule (azobenzene) that changes colour in the presence of light due to a change in conformation.
These photochromic molecules have shown promise for inexpensive optical‐based storage media, where the trans‐
isomer could be the “0” logic element and the cis‐isomer could be the “1” logic element. As illustrated in Figure 1, UV light is used to write (to form the cis isomer) while visible light is used to read (to observe the colour). This optical read process actually transforms the molecule back to the trans‐conformation, thus destroying the state of the molecule. Interestingly, the change in optical properties of organic photochromic molecules also corresponds to a change in the electronic properties (charge transport) of the material, where they switch from insulating to semi‐conducting states. In this project, you will systematically synthesize photochromic molecules to maximize the difference between the insulating to semiconductive states for use in memory devices. Specifically, you will prepare photochromic molecules (giving you experience in synthetic Organic Chemistry), study their structural, thermal, electronic and photophysical properties (giving you experience in Physical Chemistry) and possibly incorporate into prototype plastic electronic devices.
N N
t r a n s- a z oben zen e
U V lig ht
Vi si bl e lig ht
N N
cis-azobenzene
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PROFESSOR PAUL ALEWOOD GROUP LEADER, IMB
Phone: 07 3346 2982
Email: [email protected]
The research interests of our group include the discovery and total synthesis of peptide toxins from Australia’s venomous creatures, the chemical synthesis of proteins and bioactive peptides, development of new synthetic and analytical methods, heterocyclic chemistry, proteomics and bio‐‐‐organic and medicinal chemistry. Special emphasis is placed on determining the structure‐‐‐function relationships of natural and/or designed molecules.
Alpha‐‐‐conotoxins that target chronic pain Conotoxins are small bioactive highly structured peptides from the venom of marine cone snails (genus Conus). Over the past 50 million years these molluscs have developed a complex venom cocktail for each species with each venom comprised of 100‐‐‐2000 distinct cysteine‐‐‐rich peptides for prey capture and defence. This project focuses on the important and well‐‐‐studied class of a‐‐‐conotoxins which contain two disulfide bridges, 12‐‐‐16 residues and are potent and selective antagonists of nicotinic acetylcholine receptors. Specifically, we have found that there is an ‘a‐‐‐conotoxin‐‐‐like’ class of conotoxins that target the GABA‐‐‐B GPCR and are effective as blockers of chronic pain. In this project we will identify, synthesise and characterise some new leads in this class, develop peptidomimetics and evaluate them in vitro and in vivo as lead candidates for drug development.
PROFESSOR ROB CAPON GROUP LEADER, IMB
Phone: 3346 2979 Email: [email protected] Website: http://capon.imb.uq.edu.au
Biodiscovery: Biodiversity and Biology, to Bioactives and Beyond My research group focuses on the detection, isolation, characterization, identification and evaluation of novel bioactive metabolites from Australian marine and terrestrial biodiversity. These metabolites span all known biosynthetic structure classes including many molecules new to science, andtheir study requires the use of sophisticated chromatographic, spectroscopic and chemical technologies. Natural products uncovered during our investigations represent valuable new leads in the search for drugs with application in the fields of human and animal health and crop protection, have potential as molecular probes to better interrogate and understand living systems, and could find application as biological control agents.
Available Honours projects: Targeting Multidrug Efflux in Cancer: This project will develop our recent (unpublished) discovery of a marine
fungal alkaloid thatinhibit P‐glycoprotein (P‐gp) mediated multidrug resistance in human cancers. The project will optimize a practical synthesis, prepare a library of analogues, assess and document chemical properties and evaluate P‐gp inhibitory activity against human colon cancer cell lines.
Targeting Alzheimer’s Disease: This project will develop our recent (patented) discovery of a unique class of marine sponge alkaloid that inhibit kinases critical to the development of neurodegenerative diseases (e.g. Alzheimer’s). The project will optimize a practical synthesis, prepare a library of analogues, assess and document chemical properties and evaluate kinase inhibitory activity.
Targeting Cane Toads: This project will develop our recent (patented) discovery of a pheromonal attractant
capable of trapping cane toad tadpoles. The project will optimize the production and chemical derivatization of the pheromone, and the design and formulation of delivery devices, which will be evaluated in field trials.
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ASSOCIATE PROFESSOR NICK DAVIS-POYNTER UNIT HEAD, SASVRC/CMVC Phone: 07 3636 8138 Email: [email protected] Website: http://www.sasvrc.qld.gov.au?Projects.html
During the course of millions of years of evolution, herpesviruses have pirated numerous genes from the host. Our group is determining the contribution of such genes to the herpesvirus lifecycle – from the cellular to the whole animal level. Many herpesviruses, including cytomegaloviruses (CMVs), encode homologues of cellular G protein‐coupled receptors (GPCR). The GPCRs have diverse biological effects, due to their potential to invoke a cascade of intracellular signalling pathways. The project will investigate one of the viral GPCR of mouse CMV (termed M33 and M78), homologues of which are expressed by all cytomegaloviruses. Disruption of either of these genes results in profound attenuation in vivo and also affect replication in certain cell types in tissue culture, suggesting they may be novel targets for antiviral drugs. We are investigating the effects of specific mutations of M33 and M78 upon their biological functions. Mutations will be generated by site‐directed mutagenesis and the effects characterised using transfected cells and/or genetically modified mouse CMV. The student will consequently gain experience of a range of molecular biology/virology techniques. We are also determining whether the human CMV GPCR are functionally similar to those of mouse CMV. The results of these studies will improve the understanding of the function of the GPCR for the virus and indicate whether viral GPCR may be a suitable target for anti‐viral drug development. For more information, contact Nick or visit the website.
DR ANNETTE DEXTER ASSOCIATE GROUP LEADER, AIBN Phone: 07 3346 3199 Email: [email protected] Short designer peptides are attractive building blocks for the preparation of novel functional nano‐materials. Peptides offer stimuli‐responsiveness, biocompatibility, predictable folding and the capacity for sustainable production. By employing a key structural motif of native proteins, the amphipathic alpha‐helix, we have developed lineages of designer peptides that show promise as responsive hydrogels for wound healing, tissue engineering and drug delivery or separately, as environmentally‐friendly switchable surfactants.
Examples of available Honours projects include the following: Peptide hydrogels for burn healing—preparing and testing hydrogels for delivery of protein actives to burn wounds, while providing a moist wound bed conducive to improved healing.
Peptides as surfactants for eco‐friendly industrial fluids—formulating and testing cutting fluid emulsions for lubrication in metal‐working and recyclability of the oil and water components.
Bioproduction of peptides as hetero‐ or homoconcatemers—design, expression and downstream processing of a gelling peptide for biomedical use.
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ASSOCIATE PROFESSOR RALF DIETZGEN QUEENSLAND ALLIANCE FOR AGRICULTURE AND FOOD INNOVATION (QAAFI) Queensland Agricultural Biotechnology Centre (QABC), St Lucia Campus Phone: 07 3346 6503 Email: [email protected] Website: http://www.qaafi.uq.edu.au//?page=157981
Molecular Plant‐Microbe Interactions My research interest is in the discovery and biodiversity of genes, proteins and regulatory RNAs in plants and viruses and their interactions in agricultural systems. Increased knowledge of these molecular interactions will enable improved crop performance and better disease control. Special interests include the characterisation of plant‐adapted rhabdoviruses and tospoviruses, virus diagnosis and molecular evolution, RNA silencing pathways for pest and disease resistance, and functional genomics and molecular markers in tropical horticulture.
The project Plant virus movement on cytoskeletal highways and byways seeks to investigate the functions of the cell‐to‐cell movement protein (Mv) of a plant‐adapted rhabdovirus. Plant host factors that are known to interact with expressed rhabdoviral movement proteins will be investigated by live plant cell imaging using advanced protein localisation and interaction techniques and laser scanning confocal microscopy. Gateway cloning technology compatible with binary vectors for bimolecular fluorescence complementation will be used to validate interactions, while fusions with autofluorescent proteins will allow accurate determination of their intracellular location. Protein‐protein interactions will be validated by infiltration of chemicals that interrupt components of the plant cytoskeleton. GFP‐tagged viral MP will also be used to determine the mechanism of virus movement to neighbouring cells either as ribonucleoprotein complex or as virions through tubules across plasmodesmata using isolated MP‐expressing plant cells, ie. Protopla.
PROFESSOR DAVID FAIRLIE CHEMISTRY AND HUMAN THERAPEUTICS, IMB Email: [email protected] Website: http://fairlie.imb.uq.edu.au Our biology research programs investigate the pathogenesis and treatment of diseases. Biochemistry and pharmacology students use new compounds (invented by chemists in our group) to interrogate human proteins, human cells, and rodent models of human disease to elucidate mechanisms of physiological processes, disease development, and drug action. Students learn multiple techniques relevant to either protein/gene expression, enzymology, protein‐protein interactions, intracellular signaling, or rat/mouse models of human diseases. Researchers gain insights to processes pivotal to human physiology or aberrant in disease, and develop interdisciplinary skills in one or more of biochemistry, pharmacology, immunology, oncology, virology, parasitology, or neurobiology. Among projects in 2013 are: (1) G protein‐coupled receptor signaling in human cells that mediate diseases (2) Pharmacology in rodent models of inflammatory diseases (3) Inhibiting enzymes in cancer, inflammatory or neurodegenerative diseases (4) Understanding relationships between obesity, diabetes and inflammation (5) Targeting viral proteins that are essential for infectious disease
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DR MARY FLETCHER QUEENSLAND ALLIANCE FOR AGRICULTURE AND FOOD INNOVATION (QAAFI) Natural Toxins, Health & Food Sciences Precinct, Coopers Plains Phone: 07 3276 6089 Email: [email protected] Research interests focus on the identification and analysis of natural toxins in a range of plants, fungi and agricultural products and their impact on livestock and agricultural production. Such toxins have the potential to form residues in agricultural products and pose a risk to consumers. Honours projects are available in: 1. The prevalence of indospicine in Indigofera plant species by LC‐MS/MS Indospicine is an unusual amino acid in that it is not incorporated into proteins, but is present as the free amino acid and accumulates in tissues of animals fed Indigofera plant material. This project investigates the prevalence of indospicine in a range of Indigofera plant species present in Australian rangelands by liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). 2. Effect of UV light on the control of mycotoxins in maize Aflatoxin in a fungal toxin (mycotoxin) produced by fungi on agricultural crops such as maize. This project will investigate the control of the toxin by post‐harvest drying in sunlight and storage on maize infected with Aspergillus fungus and aflatoxin. This project will provide insight into areas of international food safety and aflatoxin analysis and control.
PROFESSOR ROBERT G GILBERT RESEARCH PROFESSOR, CNAFS Phone: 07 3365 4809 Email: [email protected]
Biosynthesis‐structure‐property relations for starch and glycogen Starch provides more than half the world population’s calorific intake; glycogen is our body’s glucose buffer. These are at first sight simple homopolymers of glucose, but their structure spans many levels of complexity, with features ranging from nm to mm. These structural features strongly influence nutritional value for humans, and how well glycogen is effective in controlling blood sugar (and hence propensity to diabetes). In synthetic polymer science and technology, the paradigm for understanding material properties, and producing materials with improved properties, is well established as synthesis controls structure controls properties. We are now doing the equivalent for starch and glycogen: one changes the genetics (biosynthesis) to try to obtain cereals with desirable properties—better digestibility for managing and reducing obesity, diabetes and colo‐rectal cancers—and drug targets for diabetes through glycogen synthesis enzymes. This project will greatly expand current knowledge, through our unique experimental and theoretical tools, to examine the structure of these polymers and then to relate the structural features to both biosynthesis and to properties.
Project 1: Genetics/structure relations: simulations Project 2: Genetics/structure relations: experiment
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PROFESSOR GLENN KING GROUP LEADER, IMB Phone: 07 3346 2025 Email: [email protected] Website: http://www.imb.uq.edu.au/index.html?page=56210
Venomics as a drug and insecticide discovery platform Animal venoms are increasingly important in drug discovery efforts as they constitute a vast and largely untapped source of pharmacologically active molecules. Spiders are by far the most successful group of venomous animals and their venoms are predicted to contain more than 10 million different biologically active peptides. Our group is exploring spider venoms as a source of novel peptides to provide leads for the development of new drugs and insecticides. As a major part of this initiative, we have developed a structural venomics pipeline that allows protein structures to be determined via NMR at an unprecedented rate. Available Honours projects:
Screening spider venoms for peptides targeted at ion channels involved in sensing pain, and examination of their analgesic potential in animals.
Discovery of novel insecticidal and antimalarial compounds.
Structural and functional characterisation of venom peptides.
Characterisation of the interaction between venom peptides and their ion channel targets.
Examination of the genetic basis underlying the remarkable diversity and evolution of venom peptides.
Developing methods for automated protein structure determination via NMR.
DR KIRSTEN SPANN SIR ALBERT SAKZEWSKI VIRUS RESEARCH CENTRE CLINICAL MEDICAL VIROLOGY CENTRE, RESPIRATORY VIRUS RESEARCH UNIT Phone: 07 3636 8718 Email: [email protected] Respiratory Syncytial Virus (RSV) and metapneumovirus (MPV) are significant causes of lower respiratory tract disease in infants, young children and immune‐compromised adults. They are also linked to both the inceptions and exacerbation of asthma. There are no vaccines or commercially available targeted antivirals for either RSV or MPV. We are interested in the pathogenesis of these viruses in association with asthma and acute disease, and also the identification of antiviral targets.
Project 1: There has been a recent surge in research concerning human microRNAs (miRNA) and how
these small RNA species regulate human gene expression in relation to disease. Pathogens such as viruses also regulate miRNAs, which, in turn, regulate human genes involved in the immune response. We are interested in how RSV regulates miRNAs in human cells during infection. RSV encodes specific proteins that are involved in suppressing the innate antiviral response to infection. We are interesting in investigating which miRNAs are regulated by the RSV immune‐suppressive proteins and how mimicking or inhibiting these miRNAs may affect RSV replication.
Project 2: Asthmatic adults and children may have a defect in their innate antiviral response that makes them more susceptible to viral infection and disease than healthy individuals. This has been shown for rhinovirus infection, however we are investigating defects in the antiviral response of asthmatic (and also allergic) individuals to RSV and MPV, which are paramyxoviruses. We are interesting in not only intrinsic defects of the airway epithelium of asthmatics, but also the role the viruses play in regulating the antiviral response that may underlie the risk of asthma.
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ASSOCIATE PROFESSOR RICK STURM GROUP LEADER, IMB Phone: 07 3346 2038 Email: [email protected] Website: www.imb.uq.edu.au/index.html?page=11690
Molecular genetics of pigmentation and melanoma Melanocytes produce the melanin pigments responsible for skin, hair and eye colour. Darker forms of melanin protect the skin from solar radiation exposure, however melanocytes are also the cell type from which malignant melanoma can originate. We are studying the human pigmentation system to understand the genetic basis of cellular differentiation, tissue‐specific gene expression and cellular transformation induced by solar UV light. Available Honours projects: Genetics of human pigmentation including comparing individuals of high and low mole number, and looking at genes controlling mole morphology. Cell biology of human pigmentation, whereby the laboratory is growing primary cultures of human melanocytes alone or together with keratinocytes to assay function of genes.
Specific projects listed on www.imb.uq.edu.au/index.html?page=11690
DR MATT SWEET GROUP LEADER, IMB Phone: 07 3346 2082 Email: [email protected]
Pathogen Surveillance, Innate Immunity and Inflammation My group focuses on understanding how the innate immune system detects and responds to invading microorganisms. Innate immune cells such as macrophages express a broad repertoire of pattern recognition receptors, for example members of the Toll‐like Receptor (TLR) family that detect a number of pathogen‐associated molecular patterns including LPS, CpG DNA and bacterial lipoproteins. Macrophage activation via TLRs regulates expression of genes involved in antimicrobial responses, inflammation and priming of the adaptive immune response. When such responses are dysregulated, both acute and chronic inflammatory disease can result. We study TLR signalling pathways and the function of novel TLR‐regulated genes in the context of infectious and inflammatory diseases. Key collaborators within SCMB include Professor Al McEwan, Dr. Kate Stacey and Professor Mark Schembri. Available Honours projects for 2014 include: (1) Understanding the role of histone deacetylases in TLR‐activated inflammatory pathways; (2) Characterizing human macrophage anti‐microbial pathways; and (3) Characterization of novel TLR target genes.
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ASSOCIATE PROFESSOR ROHAN TEASDALE GROUP LEADER, IMB Phone: 07 3346 2056 Email: [email protected] Website: http://www.imb.uq.edu.au/index.html?page=11682&pid=11669
Endosomal Dynamics and Pathogen Invasio The endosomal/lysosomal system of mammalian cells is a highly dynamic organelle and the trafficking pathways within the endosomal system are fundamental for a wide variety of key cellular processes. My group is developing cellular and computational approaches to identify novel mammalian proteins associated with the endosomal system. This includes the retromer complex that has recently been identified as a causal agent for Type 2 diabetes and neurodegenerative disease. Numerous infectious pathogens exploit specific endocytic pathways to invade the host. Characterization of pathogen entry pathways is essential for understanding infectious diseases but has also proven to be a powerful tool for gaining insight into normal cellular processes. We are currently investigating the molecular details of these pathways and how they are modulated in response to infection with Salmonella, a leading cause of human gastroenteritis and Chlamydia, a major sexually transmitted pathogen. Once inside the cell, these pathogens actively alter the host cells membrane trafficking pathways to create a replicative niche that enables the pathogen to survive and avoid the innate immune system in these cells. Available Honours projects:
Defining the essential host proteins required for intracellular bacterial pathogen infection. These host proteins represent attractive therapeutic targets.
RNAi screening to further define essential proteins for a range of endosome associated pathways targeted by bacterial pathogens.
Defining the molecular and cellular properties of retromer’s function in neurodegenerative diseases including Parkinson’s and Alzheimer’s.
PROFESSOR BRANDON WAINWRIGHT GROUP LEADER, IMB Phone: 07 3346 2053 Email: [email protected]
Molecular Genetics of Human Disease Our research group is focused on elucidating molecular pathology of human genetic disease, primarily through the analysis of the single gene disorder, cystic fibrosis and through the discovery of Patched, the gene responsible for both the inherited and sporadic forms of basal cell carcinoma of the skin. As a result of these studies we have a particular interest in the interface between developmental biology and human genetics, and in therapeutic strategies such as gene therapy. Projects include:
The downstream targets of patched/hedgehog signalling
Structure/function analysis of Patched
Dissection of the roles of Sonic, Indian and Desert hedgehog in development and neoplasia
The control of the host response defect in cystic fibrosis mutant mice
Genes modulated by the cystic fibrosis gene
Correction of the host response (inflammation) defect in G551D CFTR mutant mice
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PROFESSOR ANDREW WHITTAKER GROUP LEADER, AIBN Phone: 07 3346 3885 Email: [email protected] Web: www.uq.edu.au/polymer‐chemistry/ Our research group develops polymeric materials to improve human health. Our large group of researchers have programs of research across the spectrum from bench top‐to‐bedside. Specifically we work in the fields of sensing of disease, delivery of drugs and regeneration of tissue. The projects listed below are all done in collaboration with experts in clinical application of biomaterials, and will provide a solid foundation in practical and theoretical aspects of the use of polymeric materials as biomaterials. Honours projects are available in the following areas (for project details, please see our website or contact Andrew by email). The web site lists other projects.
1. Functionalisation of the surfaces of titanium alloys for improved osseointegration 2. Development of novel polymer scaffolds to aid the repair of the spinal cord 3. Development of low‐fouling, anti‐microbial surface coatings 4. Novel polymer molecular imaging agents (MRI) for early disease detection 5. Peptide hydrogels for cell delivery 6. Delivery of therapeutic drugs to the spinal cord
AFFILIATED INSTITUTIONS
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Honours projects may also be available in the following UQ Institutes that have strong links with the School of Chemistry & Molecular Biosciences:
ADVANCED WATER MANAGEMENT CENTRE Website: www.awmc.uq.edu.au
AUSTRALIAN INSTITUTE FOR BIOENGINEERING & NANOTECHNOLOGY Website: www.aibn.uq.edu.au
CENTRE FOR ADVANCED IMAGING Website: www.cai.uq.edu.au/honours‐projects
INSTITUTE FOR MOLECULAR BIOSCIENCE Website: www.imb.uq.edu.au
UNIVERSITY OF QUEENSLAND CENTRE FOR CLINICAL RESEARCH Website: www.uqccr.uq.edu.au
UNIVERSITY OF QUEENSLAND DIAMANTINA INSTITUTE Website: www.di.uq.edu.au Honours scholarships: www.di.uq.edu.au/scholarships Contact: Postgraduate Administration Officer on (07) 3176 3197 or email [email protected]
EXTERNAL INSTITUTIONS (Including SCMB ADJUNCT
ACADEMIC STAFF)
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CSIRO QUEENSLAND BIOSICENCES PRECINCT, UQ ST LUCIA CAMPUS
PROFESSOR JOHN MANNERS CSIRO Plant Industry Email: [email protected]
Potential Honours Project for 2014 Fungal pathogen species Fusarium and interactions with both Arabidopsis and wheat
PROFESSOR MARK MORRISON CSIRO Microbial Biology and Metagenomics Research Email: [email protected]
Potential Honours Projects for 2014 Bacterial mousetraps: the role of serpins in gut bacteria
How do microbes make chocolate?
QUEENSLAND INSTITUTE OF MEDICAL RESEARCH HOSPITALS COMPLEX, HERSTON
PROFESSOR JEFF GORMAN Head, QIMR Protein Discovery Centre Convenor, Proteomics Australia Email: [email protected]
Potential Honours Project for 2014 High‐Performance Proteomic Analysis of Viral Protein Post‐Translational Modifications and Interactions
with Host Cells
DR LUTZ KRAUSE Head, Bioinformatics Laboratory Phone: 07 3845 3745 Email: [email protected]
Potential Honours Projects for 2014 Discovery of biomarkers for disease onset, prognosis and personalized treatment
Comparative and Evolutionary Genomics of Human Parasites – Identifying Parasite Specific Genes, Drug and Vaccine Targets
Role of the human gut microbiota in health and disease
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Project Next‐generation‐sequencing and epigenetics – Characterizing a newly discovered gene involved in epigenetic gene regulation
Develop Support Vector Machine based predictor of candidate vaccine and drug targets against the human parasites Schistosoma spp.
Finding the needle in a haystack – Development of a web‐tool for annotating genomic variations
SIR ALBERT SAKZEWSKI VIRUS RESEARCH CENTRE CLINICAL MEDICAL VIROLOGY CENTRE, RESPIRATORY VIRUS RESEARCH UNIT
ASSOCIATE PROFESSOR IAN M MACKAY Group Leader Email: [email protected]
Potential Honours Projects for 2014 Human rhinoviruses and enteroviruses in asthma: identification, molecular analysis and clinical impact
Genome deduction and epidemiology of a recently identified parechovirus
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Opportunities exist in these industries and more:
biotechnology chemical
pharmaceutical
food processing pathology
As a Chemistry or Molecular Biosciences student, you may be able to undertake honours with companies with whom SCMB already has a working relationship. In addition, if there is a particular company you would like to work with, you are welcome to propose it to us. To find out more, express interest online at scmb.uq.edu.au/hons or by scanning this QR code.
Would you like to undertake part of your honours project in a company outside UQ?
Experience a commercial workplace
Make contacts to help you with your career
Receive support and guidance from UQ as well as your industry supervisor
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‘Honours in Industry’ project is a win‐win‐win for a student, a company and for UQ
Qi Qi He decided in the third year of her BSc studies to do Honours as a way to obtain research and other skills valued by employers. Interested in the synthesis of different kinds of new compounds related to carbohydrate chemistry, Qi Qi approached Associate Professor Vito Ferro of the School of Chemistry & Molecular Biosciences (SCMB) about a topic. Using his industry contacts, Assoc Prof Ferro found a project for Qi Qi with Brisbane‐based biopharmaceutical and drug discovery company, Alchemia Ltd, as part of SCMB’s new ‘Honours in Industry’ program. “We had encountered what looked like an interesting chemical reaction, but did not have the time to explore this due to other commercial projects,” Alchemia’s Vice‐President, Discovery, Dr Wim Meutermans, said. “It seemed an ideal honours project in terms of broad skill development (synthesis, purification, structure determination)”. Qi Qi was awarded a $2,000 Honours scholarship by SCMB and undertook her project under the supervision of both Assoc Prof Ferro at UQ and Dr Norbert Wimmer at Alchemia. “My project involved solving a real problem of the decomposition of a promising compound in the compound library at Alchemia,” said Qi Qi. “It was really interesting, and it gave me a chance to apply what I had learnt in my bachelor degree program. “Working at Alchemia’s plant exposed me to new research techniques and valuable practical skills that are specifically used in industry nowadays.” Qi Qi added that the experience gave her an insight into industrial culture and how to work on her own initiative and as part of a team. Dr Meutermans agreed that working on an industry real life problem gave Qi Qi a sense of direct applicability to it. Dr Meutermans said that Qi Qi undertook to evaluate an unusual chemical rearrangement involving an undefined kinetic intermediate. “Qi Qi successfully determined the structure, and it provided valuable information for our discovery efforts,” said Dr Meutermans. Qi Qi said that during her studies, she received “tremendous support” from her UQ and Alchemia supervisors. “They helped me to plan what I should do to succeed to solve the problem in my Honours project. They also instructed me in the lab, sharing their knowledge of chemistry, assisting me with different kinds of research techniques and teaching me valuable practical skills.” Qi Qi graduated with First Class Honours and was planning to go on to a PhD or work as a research
assistant.
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PROFESSOR JAMES DE VOSS DR JOANNE BLANCHFIELD
Phone: 07 3365 3825 Phone: 07 3365 3622 Email: [email protected] Email: [email protected]
Including a placement at:
Integria Healthcare, Eight Mile Plains, Brisbane Research area: Analytical Chemistry as applied to the Pharmaceutical industry, with particular emphasis on complementary medicine Project 1: Based in an analytical laboratory
Project 2: Based in a manufacturing facility
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PROFESSOR ROSS BARNARD
Email: [email protected]
Including a placement at:
Cook Medical, Eight Mile Plains, Brisbane Project Scope: Cook Australia, a US owned and based company, develops and manufactures medical devices for national and international markets. The Australian arm of this company manufactures an extensive range of healthcare devices that includes state of the art products for each step in the IVF process. The R&D/Engineering department at Cook Australia have established a project to investigate the washing and drying processing of products. This process step is successfully producing product cleaned of substances toxic to human embryos.
Areas of specific interest are the:Detergents ‐ chemistry of cleaning and rinsibility,Water – chemical
activity of water, andWater ‐ physical process of washing small bore tubes (needles and catheters).
Sirromet Wines, Mt Cotton With every vintage, new challenges emerge in winemaking. Over the past 5 years Queensland vintage weather conditions have varied enormously requiring constant vigilance and innovation by the winemaker to maintain consistency of quality and wine style. Project scope: Investigating the chemical basis of taste, colour, mouthfeel, and ‘pinking’ in red wine, browning in white wine and copper casse formation. Assessment of levels of phenolics, N, P, K, Fe, Cu, pH, alcohol, resveratrol and stability of proteins and effects of yeast characteristics and levels, grape varieties, altitude, soil, vintage, climate and conditions. Analysis and development of extracts to enrich red wines.