Molecular mechanisms powering a bacterial toxin injection device

Grantholders

  • Dr Ariel Blocker

    University of Bristol

Project summary

Type III secretion systems (T3SSs) are essential devices in the virulence of many Gram-negative bacterial pathogens. They translocate protein effectors of virulence into eukaryotic host cells to manipulate the cells during infection. In order to enter the narrow channel at the centre of the T3SS injection needle, substrates must carry a targeting motif and become unfolded. However, the architecture of the cytoplasmic and inner-membrane export apparatus is not well defined. In addition, it is unclear how energy from ATP hydrolysis and the proton motive force is utilised to drive substrate export. Dr Blocker plans to use a combination of genetic and biochemical studies focused around in vitro reconstitution, as well as high-resolution structural approaches, such as electron microscopy and mass spectrometry, in order to investigate these aspects of T3SSs.