Autophagy as a defence against zoonotic bacterial pathogens

Pathogenic bacteria within the food chain pose a massive health and economic cost. Recent outbreaks have demonstrated the vulnerability of our food supply to contamination and subsequent human disease.
Autophagy is a crucial response to diverse stresses, including bacterial infection. However, we understand relatively little about how the specialised autophagosome vacuole is assembled. It is thought that the autophagosomal membrane is recruited from diverse sources, yet the autophagosome itself is mostly devoid of intramembrane proteins and cholesterol. Thus specific membrane handling proteins are likely required to source, modify and assemble the autophagosome.
We have preliminary data suggesting the OSBP family of sterol-transporters are involved in both autophagy of salmonella and mitophagy (mitochondrial autophagy). You will confirm and extend these observations using gene-knockdown and functional genetic approaches. Knockdown of OSBP2 is expected to reduce autophagy of salmonella and this will be tested using imaging of infected cells. Conversely we have observed over-expression of OSBP2 drives mitochondrial fragmentation, you will test this to see if this represents induction of mitophagy and establish the functional requirements for OSBP2 triggering of mitophagy.
You will perform siRNA gene knockdown and validation, transfection and infection of human cell lines, fluorescence microscopy and quantitative western blotting.