Structure/function studies of pathogenic E. coli (EPEC/EHEC) effector molecules

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Communication between a pathogen and a host is a requirement for establishing a successful infection. Events such as non-specific/specific adhesion and modulation of host cell processes are dictated by molecular recognition events frequently mediated by protein molecules. This project funds research into a number of these processes in different host:pathogen interactions. Systems under study include the molecular mechanisms of 'effector' proteins from pathogens of mammals and plants that use a type III secretion system to directly inject proteins into host cells; molecular mechanisms of cellular adhesion by the gram positive human pathogen S. pyogenes; molecular mechanisms of 'effector' proteins from oomycete pathogens of plants. These studies include investigation into the host cell targets of these pathogenic proteins, subsequent characterization of the interaction and interpretation with respect to biological function. The primary research technique used to investigate these processes is protein structure determination by X-ray crystallography, although other solution-based in vitro biophysical/biochemical techniques are used as appropriate. In vivo studies are also an essential component of our work, frequently enabled by collaboration. This grant also supports work on investigating the mechanisms of metal binding by monomeric cupredoxins that contain a T1 copper centre and mechanisms of copper trafficking in Synechocystis species.

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