What is The Crick? - London Cancerlondoncancer.org/wp-content/uploads/2016/07/Dr... · - LRI and NIMR core budgets transferred to Crick - Wellcome Trust core funding award - allocation

What is The Crick?

• Interdisciplinary biomedical

research institute

• Partnership between:

Medical Research Council

Cancer Research UK

Wellcome Trust

UCL (University College

London)

Imperial College London

King’s College London

• 1300 scientists, 120 research

groups

• CEO: Paul Nurse

• “Discovery without boundaries”

• Develop future science leaders

• Collaborate creatively to advance

UK science and innovation

• Accelerate translation for health

and wealth

• Engage and inspire the public

Crick’s strategic priorities

• Play a national role in supporting UK science endeavour

• Focus on multidisciplinary approach to 7 big questions

The Crick science programme

4. How does cancer start, spread and respond to therapy?

5. How does the immune system know whether, when and how to react?

6. How do microbes and pathogens function and interact with their

hosts?

7. How does the nervous system detect, store and respond to

information?

1. How does a living organism acquire form and function?

2. How do organisms maintain health and balance throughout life and

as they age?

3. How can we use biological knowledge to better understand,

diagnose and treat human disease?

What’s special about the Crick?

• Size and ambition

Broad research agenda

Size allows for a critical mass spanning biomedical disciplines

Long-term support through core funding

Career structure ensures continuous renewal

• Dynamic partnerships

Increase opportunities for multidisciplinary research

Universities, Hospitals, Sanger Institute, Industry

Researcher and technology exchange

• State-of-the-art research facilities

Building designed to encourage interaction

Close to academic partners and hospitals

No traditional boundaries

• No departments or divisions

- “Interest groups” for day-to-day scientific discourse

- institute-wide activities: seminars, joint lab meetings, retreats

- external networked activities – London (partners), further afield

• Recruitment across very broad research areas

- major focus on developing outstanding young researchers

- scientific “fit” an important determinant

- long-term correction of imbalances in portfolio

• Small research groups to encourage interaction – average PI+9, max 12

• Faculty turnover

• Permeable relationship with our partners

Faculty: built-in renewal

• ~30% of PIs are senior appointments

- rolling contracts

- strategic appointments jointly with the Crick university partners

- reviewed every 5 yr by Crick international panel

• Up to 70% PIs are junior appointments: “6 + 6” career structure

- direct recruitment of outstanding young PIs setting up

- substantial core funding supports strong start and ambition

- review at 6 yr, extension for second 6 yr period

• Secondments from Crick University partners (5-6yr)

- focus on researchers establishing their programme

- interdisciplinary and clinically-oriented

• Satellite groups – short-term, grant funded, up to 3y

- major mechanism for clinical and interdisciplinary interactions

- 1-3 researchers pursuing a project jointly with a Crick group

- initially with Crick University partners

- external Crick satellites at University labs – eg physics, clinical

Permeability

• Strategic longer-term collaborative interactions

- biological making lab – microfabrication – with UCL

- Institute for Biological physics interaction hub

• Jointly supervised postdoc and graduate trainees

- joint labs – eg Crick-KCL-UCL human neuro-development group

• Open science “linklab” interactions with Pharma

• Sabbatical visitor programme

Strong foundations

• London Research Institute (Cancer Research UK)

37 research groups, director Richard Treisman

Cell regulatory mechanisms, Genomic integrity, Tumour biology

• National Institute for Medical Research (MRC)

52 research groups, director Jim Smith

Physiology, Development, Infection/immunity, Structural biology

• Initial recruitment priorities for Crick

clinical research appointments

cross-disciplinary research – computation, engineering, physics, etc

priority on junior investigators – on 6/6 programme

Graduate training

• Work with Crick partner universities

- envisage around 240 students at steady-state

- strong Crick student mentoring and support

• Non-clinical PhD programme

- registration at partner universities

- thesis committees include university members

- joint Crick-partner projects to promote interdisciplinarity

• Clinical PhD training

- with Crick partner universities, hospitals, academic health centres

- funding through NHS BRCs, competitive fellowships

- Crick CRUK clinical PhD programme with partners/CRUK Centres

Science management team

• CEO: Paul Nurse

• COO: David Roblin Translation

• Research Directors:

Steve Gamblin Science Operations

Peter Ratcliffe Clinical research and training

Jim Smith Recruitment, external relationships

Richard Treisman Recruitment, resourcing and review

• Associate Research Directors:

John Diffley Training

Julian Downward Science Technology Platforms

Malcolm Irving Crick University partners

Anne O’Garra Group leader mentoring/development

• Total budget 70% core funding, 30% response mode

• Core funding – not hypothecated

- LRI and NIMR core budgets transferred to Crick

- Wellcome Trust core funding award

- allocation proportionately greater to more junior PIs

• Response-mode funding from UK/international funding agencies:

- grants, personal fellowships to Crick scientists

- university scientists at Crick funded entirely this way

Funding and Institute Review

• Institute Review

- jointly by founders, every 5 years

- will assess progress against Crick strategy, added value

- determines funding envelope for successive quinquennium

• Building links with clinical facilities and industry

• Work with partners - share risk and reward, pool strengths and resources

• Translation team

- Translation Director – David Roblin

- Head of translation – Veronique Birault

- Entrepreneur in residence – Howard Marriage

• Translation Advisory Group – provides guidance on opportunities

• Idea-to-Innovation grants – MRC-supported development fund

• Open-science agreements with pharma

GSK linklab signed, negotiations with other companies progressing

Innovation and translation

• GSK-Crick agreement signed June 2015

• Collaboration to accelerate translation and application

- projects build on Crick biology, GSK technical resource

- researcher exchange between GSK and Crick labs

• Two senior GSK scientists work directly with Crick

- providing advice on specific projects

- scouting/scoping new opportunities.

• Joint Steering Committee oversees project approvals, progress

• 5 projects started, 8 more in the pipeline

Open science – GSK linklab

Lead

IdentificationLate Lead

Optimisation

Early Lead

Optimisation

Assay

Development

Target

Feasibility

Medicinal chemistry

and computational

molecular design

Selectivity

screening

HTS capacity

2 million

compound set

Large scale

protein

production

PK-PD

modelling

Synthetic &

analytical

chemistry

Encoded Library

technology

>109 compounds

Assay

platforms

Biopharm

affinity

maturation

Biopharm

discovery

platforms

Chemo and

expression

proteomics

GSK inputs to the Crick linklab

The laboratory design

• Four lab floors above ground

• Three floor basement:

animal, containment and

imaging facilities

• Lab space for 1300

• Lecture theatre, seminar

suite, meeting facilities

• Ground floor public access –

available to community

• GIFA: 78000 m2

A research floor

200m

70m

The last ten years...

One year on…

APRIL 2012

2007

Initial vision

Site purchased

2008 Science Planning Committee

Building design

2010 Planning permission granted

Legal agreement signed

2011 Paul Nurse appointed CEO

2012 Imperial College and KCL join

Building work starts

2013 Topping out; building fit-out

2015 Crick starts operations

2016 We’ll be in! (handover late July, all in by end November…)

WT /MRC/CRUK/UCL project board established

Who’s in the Crick on day 1?

• 87 Research groups: ex-NIMR and LRI

• 19 Partner attachments - 6 secondments, 10 satellites, 3 sabbaticals

Physical/biophysical

Computational/mathematical

Clinical/biological

Biological sciences

• Second round of attachments now offered

What’s in the Crick on day 1?

Biochemistry & Proteomics

Cell Biology

Cell Cycle & Chromosomes

Chemical Biology

Computational & Systems Biology

Developmental Biology

Ecology, Evolution & Ethology

Gene Expression

Cancer Genetics & Genomics

Genome Integrity & Repair

Human Biology & Physiology

Imaging

Immunology

Infectious disease

Metabolism

Microfabrication & Bioengineering

Model organisms

Neurosciences

Signaling & Oncogenes

Stem Cells

Structural Biology & Biophysics

Synthetic Biology

Tumour Biology

Facilities and Tech Platforms

• MRC Biomedical NMR Centre

• Worldwide Influenza Centre

• Biological Resources Facility

- Rodents

- Aquatics

- Transgenesis

- Intravital imaging

• Biological making lab (UCL)

• Advanced Sequencing

• Cell Services

• Computational Biology

• Electron Microscopy

• Experimental Histopathology

• Flow Cytometry

• Genomics / Equipment Park

• High Throughput Screening

• Light Microscopy

• Mass Spectrometry

• Metabolomics

• Peptide Chemistry

• Instrument prototyping

• Structural Biology

Food for thought….

“The motive that will conquer cancer will not be pity

nor horror; it will be curiosity to know how and

why.…”

….HG Wells

Open science – GSK linklab

Disease

knowledge

Shared

learning

Long term

relationship

Drug discovery

projects

Shared Outputs

Joint

publications

Curiosity-drivenscience

Disease expertise

Disease projects

Drug discovery

Compounds,reagents,biopharms

Discoveryplatforms

Joint inputs

Restaurant

Seminar room suite

Lecture theatre

Loading bay

Ground floor

Entry circulation

Bikes

Translatable

programmeAccelerated application

Research progress

Industrial

insights

Applied

scientists

CRICK

GROUP

Open science: route to application

Develop mechanisms to ease development of translational programmes

• Encourage inter-lab interaction and resource sharing

- open laboratory spaces to encourage interactions

- core facility laboratories scattered through building

- local administrative functions located centrally on each floor

- interaction zones at write-up space and in atrium spaces

• Different primary laboratories share dedicated secondary lab spaces

• Secondary lab spaces adaptable/interchangeable

- “kit of parts”: tissue culture, microscopes, instruments, cold, etc

Principles of the lab layout

Playing a national role

• Catalyse interaction between

biomedical research institutions

and medical schools, industry

• Technology development and

application

• Training of scientists, clinicians

and technical staff

• Health and wealth creation by

investment in medical research

Partner

universities

Other

UK HEIs

Healthcare

industries

National

Health

Service

Medical

Schools

Crick

31

34

Medicine and the Crick

• Bi-directional relationship with clinicians from our university partners

• Interaction with their associated AHSCs and BRCs

• Clinical engagement:

– allows clinical information and insights to inform discovery research

– improves access to human tissue

– enables the development of a culture of experimental medicine within

the Crick in the pursuit of translatable projects.

Benefi

ts f

or

healt

h a

nd w

ealt

h

DevelopmentOpportunity

Idea2Innovation

Discovery

Science

External funding

Crick Internal

fundingTAG*

‘Open Science’ relationships with embedded companies; academic

partners and clinicians

Accelerated Translation Capable

hands Close Distance Translation

Crick owns foreground IP to facilitate open science & accelerated translation

“in

Residence”

*Translation Advisory Group

Management and Delivery of Translational Science Tracking ImpactIdentification of Translation Opportunity

Open Science at the Crick

Close distance translation• Improve the pathway to translatable science by spotting potential

opportunities earlier

• Increase the linkages for PIs to enable CDT

• Over time as CDT becomes part of the Crick culture, the need to drive it

will reduce

Accelerated technology transfer• Acceleration of discoveries towards benefits for human health is the driver,

not value creation

• Collaborate with our academic partners and industry to develop a

multidisciplinary culture

• Projects are initiated from a sharing of scientific goals or specific areas of

endeavour

Management and communication

• Executive Committee

• Science Management Committee

- science strategy, policy, etc

• Operation Management Committee

- Finance, HR, IT, Legal, FM, Comms ….

• Science Resource Allocation Panel

- Lab resource, Tech platforms, budget planning

• Science Resource Allocation Panel

• Faculty Committee – management/group leader discussion forum

- 9 Group Leaders elpected by staff

• Science Leaders’ meeting – All Group Leaders, STP heads

• Extensive links with clinical

facilities and industry to

facilitiate translation

• Application and development

work to be encouraged

• Clinical and commercial

translation to be valued as highly

as discovery research

Innovation and translation

The Crick science programme

• National Insurance Act of 1911 put aside funds for research

(£55,000 in 1914) and TB treatment

• The Medical Research Committee was established and submitted

the first ‘scheme of research’ in 1913

• One of first decisions was to create a research institute in London

in 1914—the precursor of NIMR

• ‘Haldane Principle’ (in which MRC makes scientific decisions

independent of government) proposed in 1918

• Became the Medical Research Council in 1919

The Medical Research Council

• From one institute created in 1914, the MRC now has 54

institutes, centres and units, including units in The Gambia and

Uganda

• The MRC spent £845.3m on research in 2013/14

• MRC supports more than 4,000 people in Units and Institutes

• At any one time, the MRC supports about 390 fellows and 1,440

PhD students

• In 2013 the MRC spent £12m on Centenary Awardsx

The MRC last year

• NIMR’s first premises were in

Hampstead

• The Institute was originally run by a

committee of Directors; Henry Dale

took over as sole Director in 1928

• Construction of the Mill Hill labs began

in 1937 and scientists moved in 1949

• Officially opened in 1950 by George VI

and Queen Elizabeth

NIMR History

Genetics and Development

Neurosciences

Infections and Immunity

Structural Biology

Scientific Areas at the NIMR

• Europe’s largest cancer research organisation

- Funded entirely by public donations, no government funding

- Funds basic, translational, clinical research

- Advises / develops government cancer policy

- Provides objective information to the public

• £350m science spend – £1m every day!

- Institutes – London, Cambridge, Oxford, Manchester, Glasgow

- Grants

- Research infrastructure through Centres programme

Cancer Research UK

• 1902 Imperial Cancer Research Fund

founded, director Ernest Bashford

• 1963 Lincoln’s Inn Fields Laboratory

opens

• 1986 Clare Hall laboratory opens

• 2002 ICRF –CRC merge to form

Cancer Research UK

• 2002 LIF and CH become the London

Research Institute

History of the LRI

Science at the LRI

Hanahan and Weinberg, 2000

Scientific areas at the LRI

• Tumor - host interactions

- tissue invasion and metastasis

- angiogenesis

- stromal cell interaction

- interaction with host immunity

• Control of cell growth

and proliferation

- self-sufficiency in growth signals

- insensitivity to growth inhibitory signals

- evasion of apoptosis

- unlimited replicative potential

• Genome damage and

cancer genomics

- cancer genetics

- tumour evolution

- environmental mutagenic challenges

- endogenous mutagenic challenges

• History of Nobel Prizes:

1936 Henry Dale: role of acetylcholine as a neurotransmitter

1952 Archer Martin: invention of partition chromatography

1972 Rodney Porter: determining structure of immunoglobin

1975 Renato Dulbecco: DNA tumour virus/host interactions

2001 Paul Nurse and Tim Hunt: conservation of the cell cycle

2015 Tomas Lindahl: DNA damage and repair mechanisms

A history of discovery

• Other prizes and awards held by current faculty

- Louis Jeantet (5), EMBO medal (5), BSCB Hooke medal (3), BSDB

Waddington Medal (2)

- 14 Fellows of the Royal Society

- 24 Fellows of the Academy of Medical Sciences

- 32 Members of EMBO

Find out more…

http://www.historyofnimr.org.uk http://blueskiesbenchspace.org