Introduction

Research Groups

Select Research Group Head Prof. Sir Tom Blundell Prof. Kevin Brindle Dr Bill Broadhurst Dr Guy Brown Dr Mark Carrington Prof. Paul Dupree Prof. Gerard Evan - Head of Dept Prof. Richard Farndale Dr Giorgio Favrin Dr Jenny Gallop Dr Nick Gay Dr Andrew Grace Dr Jules Griffin Dr Brian Hendrich Dr Andrew Hesketh Dr Robin Hesketh Dr Matt Higgins Dr Florian Hollfelder Dr Hee-Jeon Hong Prof. Chris Howe Dr Marko Hyvonen Prof. Steve Jackson Dr Tony Jackson Prof. Richard Jackson Prof. Ernest Laue Prof. Peter Leadlay Dr Kathryn Lilley Dr Karen Lipkow Dr Rick Livesey Prof. Ben Luisi Dr Sarah Lummis Dr Juan Mata Dr John McCafferty Prof. Jim Metcalfe Dr Masanori Mishima Dr Eric Miska Dr Tom Monie Dr Helen Mott Dr Natasha Murzina Dr Daniel Nietlispach Dr Darerca Owen Prof. Steve Oliver Dr Luca Pellegrini Dr Markus Ralser Dr Nick Robinson Prof. George Salmond Dr Deirdre Scadden Dr José Silva Prof. Austin Smith Prof. Chris Smith Dr Nancy Standart Prof. Dame Jean Thomas Dr Aviva Tolkovsky Dr Martin Welch Dr Joyce Wong Dr Nianshu Zhang

Service & Research Support Facilities

Select by Subject or Manager DNA Sequencing Facility . . . . . Mr John Lester _______________________________ Quantitative Proteomics . . . . . Dr Kathryn Lilley _______________________________ Proteomics Core Services . . . . . Dr Mike Deery _______________________________ Protein & Nucleic Acid Chemistry . . . . . Dr Len Packman _______________________________ Metabolomics . . . . . Dr Jules Griffin _______________________________ Baculovirus Facility . . . . . Dr Darerca Owen _______________________________ Biophysics Facility . . . . . Dr Katherine Stott _______________________________ Crystallographic X-ray Facility . . . . . Dr Dima Chirgadze _______________________________ NMR spectroscopy . . . . . Dr Daniel Nietlispach _______________________________ Fermentation Facility . . . . . Dr Nianshu Zhang _______________________________ Bioinformatics & Computational Biology Services . . . . . Dr Jenny Barna _______________________________ Computer & IT Support . . . . . Dr Erik Timmers _______________________________

Past members last known active weblink

Select past member of Department Dr Stephen Bell Prof. Jonathan Blackburn Dr David Brown Dr Pak-Lee Chau Dr Hal Dixon (deceased) Dr Jessica Downs Prof. David Ellar Dr Paul Kemp Dr Simon Lovell Dr Kenji Mizuguchi Dr Massimo Paoli Prof. Richard Perham Dr Peter Reynolds Dr Philip Rubery Dr Gerry Smith Dr Margaret Sunde Prof. Jamie Vandenberg Dr Kira Weissman

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See also Cambridge Systems Biology Centre

Integrating Cellular Architecture and Signalling

Research Grouping: Functional genomics, systems biology and genetic medicine

In the true spirit of Systems Biology, we combine experiments and computer models to understand the functional relationship between cellular signalling and architecture.

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Fig. 1: Smoldyn model of an Escherichia coli cell with all molecules of the chemotaxis pathway

For their survival and correct function, cells need to sense environmental signals, react to them and transmit these from receptors to effectors. Signal transduction has been studied for decades, and many important components and principles have been identified. Equally, the internal structure of cells has been studied since the invention of microscopes, but mainly by different scientists. In the living cell, though, both components necessarily interact. We investigate the interplay of both: How signals are transmitted through a highly structured and heavily crowded cell, and how signalling influences this architecture.

Initially concentrating on the well-studied system of bacterial chemotaxis, we have pioneered a computer model to simulate the movement and reactions of thousands of molecules within a spatially structured cell. This very detailed model allowed us to make predictions on the influences of architectural features on protein distribution, molecule lifetimes and signalling speeds. We introduced and tested the concept of dynamic localisation, which enhances speed, robustness and fidelity of signalling without any cost to the cell. We are now testing these models experimentally by molecular biology and microscopy, expanding the computational analysis and extending them to other systems. This will lead to a truly integrated study of signalling and cell architecture, going back and forth between microscopy, molecular biology and mathematical and computational models. This will enhance our understanding of the questions in ways impossible with methods taken from just a single field.

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Fig. 2: Simulated diffusion trace and reaction of a single signalling molecule in a bacterial cell (duration: 100ms)	Fig. 3: Dynamic localisation model of E. coli chemotaxis

Lab members
Otavio Brustolini, Bill Collins, Robert Ross, Hugo Schmidt, Sven Sewitz

References