Award details

A novel apoptotic mode of action for a bacterial toxin

Reference	BB/C004655/2
Principal Investigator / Supervisor	Professor Richard Ffrench-Constant
Co-Investigators / Co-Supervisors	Dr Barbara Reaves, Professor Charles Streuli, Professor Jean van den Elsen
Institution	University of Exeter
Department	Biosciences
Funding type	Research
Value (£)	236,004
Status	Completed
Type	Research Grant
Start date	01/08/2006
End date	31/03/2008
Duration	20 months

Abstract

Although a wide range of bacterial effectors modulate apoptosis in host cells, none have been shown to act directly via the mitochondrion. In preliminary experiments we have shown that the Makes caterpillars floppy toxin (Mcf) appears to act by mimicking a BH3 domain only protein to promote apoptosis in both insect and mammalian cells. This is the first example of a BH3 domain containing protein that can promote apoptosis after topical application to cells. Here we will perform a series of experiments to prove that Mcf acts in a novel manner for a bacterial toxin. We will first purify enough Mcf for our studies and raise monoclonal antibodies specific to different domains of the protein. Second, we will investigate the functionality of the different domains using truncations of the protein and site directed mutagenesis of the BH3-like domain. Third, and finally, we will investigate where in the pathway Mcf acts by investigating its interaction with BcIX, over-expression of which appears to protect against Mcf mediated apoptosis. This work will not only describe the first BH3-like domain in prokaryotes but will also cast light on a protein which can be translocated across cell membranes.

Summary

unavailable

Committee	Closed Committee - Biochemistry & Cell Biology (BCB)
Research Topics	X – not assigned to a current Research Topic
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

Associated awards:

BB/C004655/1 A novel apoptotic mode of action for a bacterial toxin

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