Division of Molecular BiosciencesDepartment of Life Sciences Faculty of Natural SciencesImperial College London

Prof. Paul Freemont (Head of Division)Prof. Mike Sternberg (Deputy Head)

Molecular Biosciences

• Strategic aims -

• To understand at the molecular level (including visualisation) the function of cells as an integrated system including details of individual components and biological mechanisms which constitute the system

• To apply this information in the development of new research themes such as Systems Biology, Synthetic Biology and Drug Discovery.

Molecular Bioscience Division Profile

• Academic Staff: 19• Independent Research Fellows: 5 • Postdoctoral Fellows: 59• PhD and Master Students: 78• Grants held = £24M• Grants 06/07 spend = £6M• Collaborations and support from industry primarily in

Biopharma and Biotech.• Two Spin out companies: Equinox Pharma and

NanoBioDesign

• Integrative Systems Biology and Bioinformatics– Systems understanding of living cells and organisms at different scales

• Synthetic Biology – Design and manufacture of biologically based parts, devices and systems and redesigning existing, natural biological systems

• Atomic Biology – Imaging cells at atomic resolution using interdisciplinary structural biology techniques

• Biomedical Glycobiology – Using glycan analyses and functional studies of sugar receptors in cellular recognition with an emphasis on disease states

• Membrane Protein Structural Biology – The application of new methods to express, crystallize and solve the structures of membrane proteins focused on therapeutically important human GPCR receptors.

• Bio-Solar Energy - the artificial leaf and hydrogen production• Academic Drug Discovery and Biopharmaceutical Processing– Utilisation of

bioinformatics, protein structure and screening to facilitate drug discovery and manufacture

Interdisciplinary research themes in MBS

• Centre for Structural Biology (Prof. Steve Matthews) http://www.imperial.ac.uk/structuralbiology• Centre for Bioinformatics (Prof. Mike Sternberg)

http://www.imperial.ac.uk/bioinformatics• Centre for Integrated Systems Biology (Prof. Jaroslav

Stark)http://www.doc.ic.ac.uk/bioinformatics/CISB/

• Centre for Electron Microscopy (Profs. Marin van Heel and Paul Freemont)

• Glycobiology Training, Research and Infrastructure Centre (Prof. Anne Dell FRS) http://www.imperial.ac.uk/glycoTRIC

• Cross-Faculty NMR Centre (Prof. Steve Matthews) http://www3.imperial.ac.uk/nmrcentre

Interdisciplinary Research Centres

• Bioreactor suite• Robotic crystallisation• X-ray data collection• Bioanalytical suite • High-field NMR• Cryo-electron microscopy• Mass spectrometry• Structural Bioinformatics • High performance computing

• Run MRes in Structural Biology•

Structural Biology:Facilities and Infrastructure

CISBIC

• Centre for Integrative Systems Biology at Imperial College

• BBSRC/EPSRC funded £6M from Sept 2005 for 5 years

• But “What is Systems Biology” ?

What is Systems Biology?

Very many interpretations!

What is Systems Biology?

• Explaining and predicting biological processes by integrating knowledge about both the parts and their interactions and not just the sum of the parts

CISBIC vision

• Higher level of complexity requires an iterative cycle of wet biology and modelling

Three integrated sub-projects

Exemplar project on host-pathogen interaction

Systems Biology developments

• Research– Additional BBSRC SABR

grants led by CISBIC– Funding of a research

centre and project by Syngenta

– New appointments - Dr Robert Endres (next speaker)

• Teaching– Final year UG module– MSc in Bioinformatics and

Theoretical Systems Biology

– New MRes in Systems and Synthetic Biology (Oct 08) with CISBIC and the IoSSB

Exemplar Project

Core Facilities and Outreach

New Projects

Years 1 – 5

Data Integration

Glycoproteomics

Dell

Core Facilities

Transcriptomics

Kafatos + CSC

Cell Imaging

MageeMetabonomics

Nicholson SternbergButcher

Proteomic and Glycomics

• World leading mass spectrometry

Bioinformatics Support Service

• Dr Sarah Butcher (Head) + 5 staff• Bioinformatics software, databases and

hardware• Help via web site and e-mail help-desk • Undertake small scale and large scale support

including bespoke programming• Several grants now fund full or part posts in

BBS to deliver robust data management (now a BBSRC requirement)

• Runs training workshops

Major Collaborations

• Dr Gerard Bishop (Biology) – Sequencing the Tomato genome (2 grants)

• Dr Pietro Spanu (Biology) – Sequencing Blumeria graminis genome (1 grant)

• Dr David Leak (Biology) – Pichia protein secretion (1 grant)

• CISBIC (various)• Other collaborations ongoing with Physics,

Chemistry, Computing, Faculty of Medicine (various divisions), other universities in UK and outside

Synthetic Biology developments

• Research– Institute of Systems and Synthetic Biology (cross-

faculty)• EPSRC Science and Innovation application (April

08)• Bio-energy and bio-fuels (with Biology)• Strategic appointments in Synthetic Biology

• Teaching– Final year UG module with Bioengineering– New MRes in Systems and Synthetic Biology (Oct 08)

with CISBIC and the IoSSB

Examples of collaborations within DoLS

• Patwardhan & Onesti - Single particle e.m. of the MCM complex• Sternberg & Sinden - Functional annotation of Plasmodium• Sternberg & Christophides – Plant systems biology• Stumpf & Spanu – Fungal pathogens of plants• Stumpf & Buck – Bacterial stress response pathways• Zhang & Buck - Structural mechanisms of bacterial transcription• Matthews & Frankel - Structural basis of pathogenecity• Freemont & Mann - Structure of cell cycle phosphatases• Dell & Haslam with Crisanti - Mosquito proteomics• Dell & Halslam with Ushkariov - Proteomics• Bioinformatics Support Service….• And more….

And more collaborations

• Ernesto Cota and Pietro Spanu• Anne Dell & Stuart Haslam with

– Andreas Crisanti (Mosquito proteomics)– Yuri Ushkaryov,

Mechanisms for Collaborations

• Need to be proactive before grant announcement

• Focused workshops on themes appropriate for support by research funding bodies

• Are there realistic Departmentally-driven incentives?– e.g. should more of our small pool of PhD

students be directed towards collaborative project?