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Molecular analysis of actin-based motility of Burkholderia spp

Reference	BBS/E/I/00001335
Principal Investigator / Supervisor	Professor Mark Stevens
Co-Investigators / Co-Supervisors	Dr Edouard Galyov
Institution	The Pirbright Institute
Department	The Pirbright Institute Department
Funding type	Research
Value (£)	70,880
Status	Completed
Type	Institute Project
Start date	01/10/2007
End date	30/09/2010
Duration	36 months

Abstract

Control of actin assembly is essential for a plethora of cellular processes. In addition, subversion of actin dynamics by facultative intracellular pathogens facilitates their entry and exit from host cells, with key implications for pathogenesis. The study of bacterial and viral actin nucleators has yielded fascinating insights into the composition and regulation of protein complexes at sites of actin assembly and provided cell-free models to study lamellipodia and filopodia formation. With support from the BCB Committee, we recently identified a family of novel Type V secreted proline-rich actin-binding proteins that mediate actin-based motility of Burkholderia spp. by stimulating the continuous polymerisation of actin at a single pole. The structure, function and interactions of B. pseudomallei BimA and its orthologues are not understood. Here we propose to identify BimA domains required for actin binding, polymerisation and motility by site-directed mutagenesis and examine if its activity is regulated by phosphorylation and/or glycosylation as predicted. The protein complex assembled by BimA will be analysed and interacting partners localised to B. pseudomallei-induced actin tails in vivo and added to in vitro reconstitution assays. The composition of protein complexes assembled by BimA orthologues from related species will also be assessed to determine if they stimulate actin-based motility by distinct mechanisms.These studies will simultaneously dissect the mode of action of key microbial virulence factors and produce important new knowledge on the regulation of cellular actin dynamics.

Summary

unavailable

Committee	Not funded via Committee
Research Topics	Animal Health, Microbiology
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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