Research Groups
Introduction
Blundell Brindle Broadhurst Brown Carrington Dupree Evan  Head of Dept. Farndale Gay Grace Griffin Hendrich Hesketh Higgins Hollfelder Hong Howe Hyvonen Jackson S Jackson T Jackson R Laue Leadlay Lester Lilley Lipkow	Livesey Luisi Lummis Mata McCafferty Metcalfe Mishima Miska Monie Mott Murzina Nietlispach Owen Oliver Packman Pellegrini Robinson Salmond Scadden Silva Smith A Smith C Standart Thomas Timmers Tolkovsky Welch Zhang
Past members

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
Hugo Schmidt

References