OCISB: From small to large networks and back, BBSRC Systems Biology Workshop

BBSRC Systems Biology Grantholder Workshop, University of Nottingham, 16 December 2008.

Judy Armitage: Bacterial sensory networks. The e.coli chemotaxis system is probably the best-understood "system" in biology, where biases in swimming direction are provided by regulating motor switching. The chemotaxis pathway is a paradigm for HPK-RR (histidine protein kinase – response regulators) pathways. There can be over 100 HPK pathways in a single species. OCISB projects include: extend E.coli models to species with two or more chemosensory pathways, and extend these to HPKLRR pathways in general to allow prediction of partners. They started with R.sphaeroides, her "favorite" bacterium. This bacterium has 2 targeted pathways preventing crosstalk. They gave the generated data sets to the modelling groups and asked if proteins operating in parallel or linear pathway? The control theory people came up with 4 models that fit the data, but 3 could be excluded based on perturbation tests in vivo. The same data was given to mathematical biologists.

Modelling was with ODEs (temporal dynamics), and partial DE (for spatiotemporal dynamics). Porter et al (2008) PNAS online, showed how histidine kinase CheA3 is also a specific phosphatase for CheY6-P, one of the 6 motor binding proteins – tuning kinas:phosphatase will control motor switching. Further, there must be a link between cytoplasmic cluster and polar kinase. CheB2~P phosphorelay allows response to environment to be tuned to metabolic need. How common is this and how is discrimination achieved? CheA (HPK) CheY/CheB (RR). Modelling MCP Helix mutants with the sidekick tool – a coarse-grain transmembrane (TM) pipeline.

These are just my notes and are not guaranteed to be correct. Please feel free to let me know about any errors, which are all my fault and not the fault of the speaker. πŸ™‚

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