Award details

Robustness and sensitivity of intracellular signals in bacteria

Reference	BB/C513350/1
Principal Investigator / Supervisor	Professor Philip Maini
Co-Investigators / Co-Supervisors	Professor Judith Armitage, Dr Marcus Tindall
Institution	University of Oxford
Department	Mathematical Institute
Funding type	Research
Value (£)	343,513
Status	Completed
Type	Research Grant
Start date	01/07/2005
End date	30/06/2008
Duration	36 months

Abstract

E. coli chemotaxis is probably the best characterised behavioural system in biology, with all the proteins identified and 30 years of molecular genetics and biochemistry addressing the signalling pathway. Extracellular signals are sensed by a limited number of transmembrane receptors and cause a change in activity of a histidine kinase, controlling the phosphorylation, and hence affinity, of a diffusible protein. When phosphorylated this protein has reduced affinity for the kinase, but increased affinity for the rotary motor of the flagellum. It therefore binds the motor and causes it to switch rotational direction and thus causes the cell to change the direction in which it is swimming. However, despite the level of biochemical, structural and molecular understanding theoretical models have still not been able to account for the incredible sensitivity and gain of the system: most bacteria can respond to a change of a few molecules over a background extracellular concentration ranging across 5-7 orders of magnitude. While the E. coli pathway is the best understood pathway, it probably reflects the chemosensory pathway of only a limited number of bacterial species. Most species whose genomes have been sequenced have multiple homologues of the chemosensory genes, additional chemosensory proteins, cytoplasmic receptors, or all three. We will initially use the E. coli data and current models and identify parameters that may allow a more accurate understanding. These will be checked against experiments and new parameter values will be fed into existing as well as newly developed mathematical models. We are able to change the stoichiometry of individual and groups of chemosensory proteins in vivo, we can measure the diffusion kinetics of individual proteins within the cell and we can measure the in vivo kinetics of protein:protein interactions. These data will inform the mathematical models. We will then expand the model and the experiments to a more complex, but also well understood and genetically tractable species, Rhodobacter sphaeroides. This species is not only metabolically flexible, but is also has two chemosensory pathways, one targeted to polar patches and one in a cluster in the cytoplasm. We will examine protein diffusion, interaction and behaviour in this species and develop the mathematical models to address this more complex system. We hope to develop a generic mathematical model, validated against experiments, that will be usable by everyone working on bacterial chemotaxis and those working on related sensory pathways, that regulate gene expression in all bacterial species and also a range of essential physiological adaptation in eukaryotes from yeast to higher plants.

Summary

unavailable

Committee	Closed Committee - Plant & Microbial Sciences (PMS)
Research Topics	Microbiology, Systems Biology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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