“ADP-ribosylation in bacterial immunity and biotic interactions”

Host: Professor Sarah Coulthurst  

Venue: Sir Kenneth and Lady Noreen Murray Seminar Room, CTIR 284, Discovery Centre.

Abstract 

ADP-ribosylation signalling is part of the immune response of eukaryotes and prokaryotes. Upon viral infection of eukaryotes, ADP-ribosylation is catalyzed by an interferon-induced subset of ADP-ribosyltransferases (“antiviral PARPs”), which leads to the production of proinflammatory, antiviral cytokines to suppress viral replication. Yet, viral macrodomains encoded by viruses such as SARS-CoV-2 have evolved to counteract PARP-mediated response, thus representing promising antiviral drug targets. In my talk, I will present our collaborative work on SARS-CoV-2 for the discovery and development of NSP3 macrodomain small molecule inhibitors. In prokaryotes, ADP-ribosylation is employed in interspecific interactions including conflicts between phages and respective hosts. My research focuses on the structural and biochemical characterisation of novel enzyme systems involved in such conflicts. DarTG is the first discovered toxin-antitoxin system utilising ADP-ribosylation, and is found in a variety of prokaryotes including global pathogens. I will present our findings on DarTG families known so far and the role of DarTG2 in the regulation of growth in Mycobacterium tuberculosis