Modern biotechnology Dr Nataporn Chanvarasuth

Technical Session ICurrent Global Trends in Emerging Technologies and Approaches to Harness them for Development

Modern biotechnology

Year 2030 Bioeconomy

OECD: The bioeconomy in 2030 is likely to involve three elements: 1. advanced knowledge of genes and complex cell processes2. renewable biomass3. integration of biotechnology applications across sectors.

OECD = the Organization for Economic Co-operation and Development

1. Fuel-cell vehicles *2. Next-generation robotics3. Recyclable thermoset plastic4. Precise genetic-engineering techniques

*5. Additive manufacturing *6. Emergent artificial intelligence7. Distributed manufacturing8. Sense and avoid drones 9. Neuromorphic technology10. Digital genome *

http://www.scientificamerican.com/article/top-10-emerging-technologies-of-20151/?page=2

Top 10 Emerging Technologies of 2015

Advanced Knowledge of Gene: Molecular Technology

Blueprint of Life:

• DNA (Deoxyribonucleic acid): macromolecule made up of small subunits called nucleotides (A,T,C,G)• Genes: segment of DNA that determine specific traits• Chromosomes: coiled strands of DNA http://www.mayoclinic.org/tests-procedures/genetic-testing/multimedia/genetic-disorders/sls-20076216?s=1

Mutation: A change in the base sequence of DNA can affect the structure and function of proteins

http://www.vce.bioninja.com.au/aos-3-heredity/molecular-genetics/mutations.html

Genome sequencesBacteriophage MS2 Bases: 3,569

Chromosomes: 1

Saccharomyces cerevisiae or Baker’s yeast

Bases: 12.1 million Chromosomes: 32

Arabidopsis thaliana or Arabidopsis

Bases: 119 million Chromosomes: 5

Drosophila melanogaster or Fruit fly

Bases: 165 million Chromosomes: 4

Homo sapiens or Human

Bases: 3.2 billion Chromosomes: 23

http://www.yourgenome.org/facts/timeline-organisms-that-have-had-their-genomes-sequenced

DNA sequencing Technology

Sanger sequencing• determine genetic code based on capillary electrophoresis separating fragments of DNA by size and sequences them by detecting the final fluorescent base on each fragment• time-consuming & expensive

Next-generation sequencing• known as high-throughput parallel sequencing• sequence larger amount of DNA• generate massive data• faster and cheaper than Sanger sequencing

http://www.slideshare.net/ueb52/introduction-to-next-generation-sequencing-v2

Third generation (gen-3) • single-molecule sequencing technology platform• sequence DNA directly-eliminating much of the sample preparation• platform used DNA polymerase and nanopore technology• detect ion current level • suitable for diagnostic tools

http://www.genengnews.com/gen-articles/third-generation-sequencing-debuts/3257/?page=2

DNA sequencing Technology

https://sites.google.com/site/dnasequencingandtechnology/thirrd-generation-sequencing

DNA/genome sequences + digital technology = digital genome

Digital genome is the genetic make-up which can be displayed in computer and shared via internet

DNA Barcode to identify and classify living things

http://ibol.org/about-us/what-is-dna-barcoding/

https://sg.idtdna.com/pages/decoded/decoded-articles/your-research/decoded/2012/06/15/barcoding-life

Pharmacogenomics in the pocket

Medicine safety code (MSC) exists from the knowledge of personal genomic profiling and barcode technology to support clinical decision and increase safety of medical treatment

http://jamia.oxfordjournals.org/content/20/3/409

Web-based platform “TraitAbility” for global vegetable industry.

DNA fingerprint is a set of DNA markers

Genetic markers are desirable genes that are transmitted by the standard laws of inheritance from one generation to the next.

Scientists use the genetic markers as a shortcut for genetic studies.

Plant breeders use the marker assisted selection to select desired traits.

Medical doctor use genetic markers for better diagnosis and treatment.

Marker Assisted Selection for plant molecular breeding

http://www.nexsteppe.com/developing-sorghum-as-a-dedicated-energy-crop/

The breeder won’t have to wait until the next generation is fully grown to select plants carrying the desired traits. The next generation can be screened for the trait at any time

http://www.oriongenomics.com/products-biomarker-pipeline.html

Orion developed MethylScope® and MethylScreenTM technologies used to scan the entire human genome to discover and validate novel cancer biomarkers.

Orion found 150 novel validated cancer biomarkers for 14 most common cancers

FoundationOne provides a fully informative genomic profile used as cancer treatment decision tools by matching each patient with targeted therapies and clinical trials that are relevant to the molecular changes in their tumor based on the most recent scientific and medical research.

Personal genomic profiling leads to • a clearer understanding of risk of genetic disease • individualized treatments and targeted therapies

Explore DNA family’s origins • Early prevention from diseases • talents• medicament response

• DNA proflie • family finder

$99 $99 499 euro $199 – 499 $99

Cancer biomarker

Chula GenePro provided personalized diagnosis services using molecular technology and biomarker research

Knowledge of molecular technology leads to the needs to manipulate genes for improvement

It involves the isolation, manipulation and

reintroduction ofDNA into cells or model

organisms.

http://biologyboom.com/genetic-engineering/

One way to modify gene is “ genetic engineering ”

http://www.convergencerevolution.net/#!history/c1lw3

Aims to introduce new characteristics into organisms. For example,• Make a crop resistant to herbicide, high yield • Introducing a novel trait ex. drought resistance, resistance to

diseases • Producing a new protein or enzyme

http://www.biotech-now.org/food-and-agriculture/2014/10/get-to-know-gmos-month-continues-with-the-science-behind-gmos

Benefit of genetic engineering technology to agriculture

Leverage core capabilities in genomic platform

Agricultural seeds: GM, marker-assisted breeding, hybrid Objectives: increase yield, diseases and weed control resistance, increase Nutrition ex. SDA Omega-3 soybeans

Integrated farming systems: breeding technology + equipment technology

Technology focus area• Plant biotechnology• Plant breeding• Protein and nucleic acid technology• Precision agriculture• Computational biology and bioinformatics• Imaging and sensing• Automation• Ag chemistry, formulation & biologics

Aqua BountyTechnologies developed GM salmon by inserting genes from other fish to an Atlantic Salmon. The gene contains a growth hormone gene from a Chinook Salmon and a genetic “on switch” from a fish known as the Ocean Pout

Genome + gene-targeting technology = precision Genome editing or genome editing with engineered nucleases (GEEN) is a type of genetic engineering in which DNA is inserted, replaced, or removed from genome using artificially engineered nucleases.

There are four families of engineered nucleases: zinc finger nucleases (ZFNs), Transcription Activator-Like Effector Nucleases (TALENs), the CRISPR/Cas system, and engineered meganuclease

https://en.wikipedia.org/wiki/Genome_editing

CRISPR Gene Editing

CRISPR Cas9 or CRISPR associated protein 9 is an RNA-guided DNA endonuclease enzyme associated with the CRISPR (Clustered Regularly Interspersed Palindromic Repeats). It is a system recognizes specific patterns of DNA and then cut DNA into pieces. This is the way that bacteria target specific DNA.

In 2013 Dr. Zhang (MIT) and Dr. Church (Harvard U.) modified this mechanism and turn it into a powerful tool to cut human genomic DNA at desired location.

Ability to cut DNA or genes at specific locations allows ability to replace them with new or repaired ones.

http://www.technologyreview.com/news/542616/first-gene-edited-dogs-reported-in-china/

Lai and Gao Xiang, two scientists at Nanjing University, China use gene editing known as CRISPR-Cas9 to create a beagle with double the amount of muscle mass by deleting a gene called myostatin.

These dogs are expected to have stronger running ability. They are good for hunting and military application.

DNA mutation in the myostatin gene can be occurred naturally. The left dog lacks of myostatin gene.

Genome editing technology:

DuPont partnered with Caribou Bioscience, spin off company from U. California, Berkeley for growing corn and wheat plants edited with CRISPR in greenhouses and will do field trials next spring. DuPont predicts CRISPR will be on dinner plates within 5 years.

DuPont is testing CRISPR to make drought-resistant corn and has a growing list of plants types: soybeans, rice, and potatoes.

Now, US Department of Agriculture told several companies that it will not regulate these plants because they don’t contain genes from other species.

http://www.technologyreview.com/news/542311/dupont-predicts-crispr-plants-on-dinner-plates-in-five-years/?ref=rss&utm_source=pulsenews&utm_medium=referral

Genome editing technology: a new technology to manipulate genes to produce better products by using chemical compounds such as special enzymes and nucleic acids to genetically modify genes or replacing targeted DNA parts.

Researcher at Japan’s Fisheries Research Agency use genome editing technology to improve the function of appetite-regulating genes.

The enzyme is injected into tiger puffers resulting tiger puffers have grown much more cutting the raising period by half from two to one year.

http://asia.nikkei.com/Japan-Update/New-tech-allows-scientists-to-develop-better-fishery-agricultural-products?page=1

Genomic knowledge leads to ability to design and build organisms or novel biological systems.

1) The design and fabrication of biological components and systems that do not already exist in the natural world (create artificial life)

http://syntheticbiology.org/Abstraction_hierarchy.htmlhttp://syntheticbiology.org/FAQ.html

2) The re-design and fabrication of existing biological systems (create a system that acts unnaturally)

http://fmm.mbc.nctu.edu.tw/http://syntheticbiology.org/FAQ.html

Synthetic biology

Custom built microbe

Use baker yeast to produce plant-based products: • plant hormone ex. auxin• painkilling drugs ex. Opium poppies • anti-malarial drug ex. Artemisinin • sweetener ex. Stevia• flavor ex. vanilla http://rebeccasthompson.com/2015/08/14/engineered-yeast-turns-sugar-into-painkiller/

http://www.washington.edu/news/2015/06/30/uw-team-programs-solitary-yeast-cells-to-say-hello-to-one-another/

Create viruses, without natural usual reproductive methodResearchers from Novartis and J. Craig Venture Institute built H7N9 viruses from looking at the genetic code for vaccine production.

http://www.popsci.com/science/article/2013-05/flu-researchers-custom-make-vaccine-week

Develop biobased alternatives to petroleum-based products usinga combination of synthetic biology and chemistry

Plan to produce isobutanol for market application ex. Solvent, feedstocksFor the production of synthetic rubber, plastics, and polyesters

Cellulosic butanol technology

Robust yeast with metabolic pathway change

LanzaTech use its in-house synthetic biology capability to engineer and develop microbe for desired application.

Myriant produces renewable chemical using microorganisms with altered metabolic pathway

DuPont developed bioprocess with an engineered Escherichia coli strain that converses glucose to 1,3-propanediol (PDO). The bio-based PDO is more attractive than petroleum-based for polymer and chemical industries.

DuPont uses PDO to make its Sorona (brand of polypropylene terephthalate

http://pubs.acs.org/cen/coverstory/8126/8126greenchemistry.html

Cargill and Evolva will introduce their sweetener produced via fermentation rather than from stevia leaf in 2016

Steviol glycosides extracted in the stevia leaf with tiny quantities (less than 0.5% by dry weight) is not commercially viable.

Genetically engineered baker’s yeast can convert sugars into glycosides via fermentation.

EverSweet will be used in zero-calorie cola, fruit waters, sweet teas, lemon-lime sodas, etc.

http://www.cargill.com/news/new-zero-calorie-sweetener-hits-the-market/index.jsp

Thailand Bioresource Research Center (TBRC)

Renewable biomassEU defines bioeconomy as sustainable production and conversion of biomass for a range of food, health, fiber, industrial products and energy, where renewable biomass encompasses any biological material to be used as raw material

http://www.slideshare.net/Biorefinery/biotechnological-routes-to-biomass-conversion

2 related platforms to change biomass into valuable products• sugar platform (hydrolysis)• thermochemical platform (gasification & pyrolysis)

General Biomass company is developing advanced industrial enzyme which convert nonfood cellulosic feedstocks to sugars for bioplastics, sustainable packaging, renewable chemicals and biofuels. Advanced engineered enzymes include cellulase and hemicellulase.

http://www.generalbiomass.com/aboutgb1.htm

Penn State researchers have developed a microbial electrolysis cell, called BEAMR, to produce hydrogen. The process uses engineered bacteria to break down organic material such as acetic acid and cellulose. A small external burst of voltage aids in boosting hydrogen production.

http://www.technologyreview.com/news/409088/making-fuel-from-leftovers/

Bio-fuel cell: bio-hydrogen producer

Eiamburapa Co.Ltd. partnered with National Innovation of Thailand (NIA) and NEDO of Japan invest on a pilot plant to produce bioethanol from cassava pulp. Eiamburapa is a starch company for export.

Pilot plant was established in 2014 and able to produce 800 liter/round with 30 million baht investment from

http://www.manager.co.th/Science/ViewNews.aspx?NewsID=9570000044942

NEDO = New Energy and Industry and Industrial Technology Development Organization

http://www.slideshare.net/patrickdixonfuturist/convergent-technologies-future-of-nanotech-biotech-and-digital-innovation-conference-keynote-speaker

Additive manufacturing

Additive manufacturing or known as 3D printing refers to various processes used to synthesize a three-dimensional object.

http://techli.com/2012/07/organovo-bioprinting/#.

To print a 3D object, the manufacturer uses a 3D computer-aided design (CAD) program to create a digital model with very thin cross-sections called layers. The 3D printer builds up successive layers of material until the object is finished.

http://3dprintingindustry.com/2013/08/01/nasa-awards-project-for-3d-bioprinting-anything-you-want/

12 things produced by 3D bioprinter for medical purpose1. Tissue with blood vessels2. Low-cost Prosthetic parts3. Drugs4. Tailor-made sensors5. Tumor models6. Bone7. Heart valve8. Ear cartilage9. Medical equipment10. Cranium replacement11. Synthetic skin12. Organs

http://scienceroll.com/2015/02/19/twelve-things-we-can-3d-print-in-medicine-now/

Materialise is a leader in additive manufacturing (AM) that has strength in software design for 3D products. • make the prototypes niche products. • innovation tool for biomedical research

FDA approved the first non-metal 3D printed polymer for human implantation.

http://www.3dprinter.net/anatomical-heartprint-from-materialise

Medical image data virtual reconstruction 3D printed result

Biomedical engineering software and service

Surgical solution for surgeons

Webinar: accurate evaluation of implant placement

Organovo designs and creates functional 3D human tissues, called exVive3DTM, for use in medical research and therapeutic applications. This can accelerate the drug discovery process with lower cost.

http://www.organovo.com/tissues-services/exvive3d-human-tissue-models-services-research/exvive3d-liver-tissue-performance/

Organovo offers contract testing services utilizing exVive3DTM liver models. The model is used to provide predictive liver tissue-specific toxicity marker assessment as a supplement to in vitro and preclinical (non-GLP) animal testing

Organova partnered with Uniquest to grow kidney tissue from induced pluripotent stem cells (iPSCs) for drug screening, disease modeling and cell therapy

Startup company designs bone using bone multipotent stem cell, nutrient for cell, biomaterial, CT-scan, and implantation

Researchers at Biological Engineering, Faculty of Engineering, King Mongkut’s University of Technology Thonburi developed cell sheet engineering.

Stem cells are cultivated on temperature-responsive polymer. During the cultivation, polymer at 37 Celsius becomes hydrophobic and when the temperature is decreased into 20 Celsius, polymer becomes hydrophilic and separate from tissues. Tissue will be used for transplantation.

http://www.bioeng.kmutt.ac.th/en/program

Tissue engineering

LemnaTec developed research platform for digital plant phenotyping by combining software systems for data collection, image processing and data analysis with reliable hardware platform.

High-throughput plant phenotyping and data accumulation

Smart Agriculture

Sensors for • temperature• moisture• carbon dioxide• hydrogen• photosynthesis

http://applications.nam.lighting.philips.com/blog/index.php/2014/05/12/philips-develops-new-led-light-recipes-for-indoor-farming/

Philips & Green Sense Farms (GSF) develop indoor farming with LED “Light recipes” that help optimize crop yield and quality

Precision farming at GranMonte Smart Vineyard

Multi-function and multi-dimension sensors assist the farmers to monitor the vineyard closely from the internet or mobile phone. • The weather sensors monitor humidity, temperature, mass movement of the air, rain accumulation and sunlight energy in vineyard. • The soil sensors measure the humidity and temperature of soil around the vines area.• Video image array help vintners to follow through the activities in vineyard. • Electronic nose is employed to track the soil chemical conditions and aroma molecules. GPS tracking is employed to optimize energy and input

http://nanotech.sc.mahidol.ac.th/121229182259p/i-sense/smartvineyard_eng.html

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Technology is a core innovation driver