POSTERS - BLAST X - University of Utah

BLAST X Poster #6
USING CONTROL THEORY TO ELUCIDATE CONNECTIVITY IN R. SPHAEROIDES
CHEMOTAXIS
Mark A. J. Roberts 1 , Elias August 2 , Judith P. Armitage 1 and Antonis Papachristodoulou 3
1
Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK
2
Control Group, Department of Engineering Science, Oxford University, Parks Road, Oxford,
OX1 3PJ, UK
3
Oxford Centre for Integrative Systems Biology, Department of Biochemistry, South Parks Road,
Oxford, OX1 3QU, UK
With an increasing number of sequenced bacterial genomes it becomes evident that the
chemotactic sensory mechanism of bacteria is more complex than E. coli. In this poster we
describe how ideas from engineering control theory can be used to develop a novel approach
for designing experiments in order to elucidate the biochemical network structure of signalling
pathways in general. The goal is to develop a systematic approach for finding the best
experiment that will delineate the network structure.
We then apply this method to the chemotaxis pathway of R. sphaeroides, which has
multiple homologues of the E. coli proteins. To achieve this we are constructing, in silico,
various possible models of R. sphaeroides chemotaxis that can explain experimental
observations. These models include the different possible interactions for the CheB and CheY
proteins. Applying results from optimal control theory, we determined the best input (ligand)
profile that gives an output which would allow us to discriminate best between the proposed
models, aiming to invalidate some of them. This input ligand profile is then administered to R.
sphaeroides in a flow cell and the response is measured using a tethered cell assay. We have
also developed methods to determine the best initial conditions to discriminate between the
models, based on the limitations of what can be implemented biochemically, and these were
then also tested in a tethered cell assay.
We used the experimental results from these designed tethered cell experiments to
invalidate some of the proposed network structures and hence suggest a probable network
connectivity for the multiple CheY and CheB proteins within R. sphaeroides.
This is an exciting approach to determine network structures in a fast and efficient
manner and can be applied to a wide range of signalling pathways as well as potentially
allowing chemotaxis pathways in other species using published genomes to generate the
necessary models.
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