Project: Understanding and exploiting programmed cell death pathway during intracellular infections
Intracellular infections remain a major problem of human health and the rise in antibiotic resistance threatens to bring us back to the pre-antibiotic era, where infectious diseases killed millions of people. We therefore require novel strategies that not only target the bacteria, but also improve host defence. Although programmed host cell death (i.e. pyroptosis, necroptosis, apoptosis) is thought to play an important role in controlling these pathogens, defects in individual pathways of programmed cell death often only cause minor defects in the in vivo control of such infections. This is likely related to redundancy that evolved in response to pathogen evasion strategies, which allows the host to compensate for evasion of one pathway through the activation of another. However, we know very little about the organisation, regulation and utilization of this system of redundancy in cell death pathways. New findings from generated in a collaboration between the Bedoui group at the Doherty Institute and the Herold group at the Walter and Eliza Hall Institute suggest that a backup system allows the host to flexibly utilize different pathways of programmed cell death to eliminate infected cells. Building on these novel insights, we are seeking a highly motivated PhD student with a BSc (Hons)/MSc degree in immunology, biology, biochemistry or microbiology to investigate how this backup system works at the molecular level; how the different types of infected phagocytes utilize the system in vivo to maintain control of Salmonella; and if this system can be manipulated for therapeutic purposes.
The Bedoui group uses models of viral and bacterial infections to study how the innate and the adaptive immune systems interact. Key foci are to understand how innate cells sense pathogens and how this information is integrated into T cell responses that control infections and cancer.