Research group leaders
Karen Lipkow
In the true spirit of Systems Biology, we combine experiments and computer models to understand the functional relationship between cellular signalling and architecture. We concentrate mainly on two systems:
1. The chemotaxis pathway of Escherichia coli, which helps the bacteria to find the optimum environment: This is arguably the best-studied signal-transduction system in Biology, allowing us to go far beyond piecing it together, finding subtleties and major concepts that are valid for all organisms. We study how the signalling proteins are distributed and shuffled inside the cell, how the spatial organisation reacts to signalling state and in turn influences signalling properties such as speed, robustness and fidelity.
2. Transcription factor target finding in Saccharomyces cerevisiae: We study how transcription factors move around the nucleus, and whether we can detect any physiological advantage to the fact that the target genes of most transcription factors are spatially clustered, using the example of the yeast copper resistance system.
Computationally, our favourite method is a particle-based simulation algorithm, in which the movements and reactions of every relevant molecule are modelled at high spatio-temporal detail. However, depending on the scientific question, we adjust our scope from concentrations to protein domains to single atoms. Experimentally, we test our modelling predictions using standard and advanced micro- and molecularbiological techniques and quantitative fluorescent microscopy.
Lab members: Jeremy Bancroft, Bill Collins, Robert Ross, Hugo Schmidt, Sven Sewitz
Visit web page at Cambridge Systems Biology Centre
Key publications:
1. DePristo, M.A., Chang, L., Vale, R.D., Khan, S.M., and Lipkow, K. (2009). Introducing simulated cellular architecture to the quantitative analysis of fluorescent microscopy. Progress in Biophysics and Molecular Biology 100, 25-32.
2. Lipkow, K., and Odde, D.J. (2008). Model for Protein Concentration Gradients in the Cytoplasm. Cellular and Molecular Bioengineering 1(1), 84-92.
3. Bray, D., Levin, M.D., and Lipkow, K. (2007). The Chemotactic Behaviour of Computer-based Surrogate Bacteria. Current Biology 17(1), 12-19. Featured article, highlighted by the journal cover and a dispatch by M. Kollmann and V. Sourjik in Current Biology 17(4), R132-R134.
4. Lipkow, K. (2006). Changing Cellular Location of CheZ Predicated by Molecular Simulations. PLoS Computational Biology 2(4), e39.