Following a generous donation, the BSDB has instituted the Dennis Summerbell Lecture, to be delivered at its annual Autumn Meeting by a junior researcher at either PhD or Post-doctoral level. The 2017 lecture awardee was Helen Weavers (School of Biochemistry, Faculty of Biomedical Sciences, University of Bristol) was with her submitted abstract “Understanding the inflammatory response to tissue damage in Drosophila: a complex interplay of pro-inflammatory attractant signals, developmental priming and tissue cyto-protection”. Her award lecture was presented at the Autumn Meeting 2017, jointly organised by the BSDB together with the Swedish, Finish, Norwegian and Danish Societies of Developmental Biology, 25-27 October 2017 in Stockholm.
Helen’s work so far
Understanding the inflammatory response to tissue damage in Drosophila: a complex interplay of pro-inflammatory attractant signals, developmental priming and tissue cyto-protection
Helen Weavers, Bristol, UK
An effective inflammatory response is pivotal to fight infection, clear debris and orchestrate the repair of injured tissues; however, inflammation must be tightly regulated since many human disease pathologies are a consequence of inflammation gone awry. Using a genetically tractable Drosophila model, I use precise genetic manipulation, live imaging and computational modelling to dissect the mechanisms that activate the inflammatory response to tissue damage and those that simultaneously protect the regenerating tissue from immunopathology. Upon tissue damage, immune cells (particularly neutrophils and macrophages) are recruited into the damaged area by damage signals (danger-associated molecular patterns, DAMPs) released from the injured tissue. In collaboration with computational biologists, we employ a sophisticated Bayesian statistical approach to uncover novel details of the pro-inflammatory wound attractants, by analysing the spatio-temporal behaviour of Drosophila immune cells as they respond to wounds. We show that the wound attractant is released by wound edge cells and spreads slowly through the tissue, at rates far slower than small molecule DAMPs such as ATP and H2O2. Strikingly, we also find that immune cells must be developmentally ‘primed’ by uptake of apoptotic corpses before they can respond to these damage attractant signals. Such corpse-induced priming is an example of “innate immune memory” and may serve to amplify the inflammatory response in situations involving excessive cell death – and otherwise limit an overzealous and damaging immune response. Indeed, whilst inflammation is clearly beneficial, toxic molecules (e.g. reactive oxygen species, ROS) generated by immune cells to fight infection, can also cause significant bystander damage to host tissue and delay repair – and may underpin chronic wound-healing pathologies in the clinic. To counter this, I find that wounded Drosophila tissue employs a complex network of cyto-protective pathways that promote tissue ‘resilience’, which both protect against ROS-induced damage and stimulate damage repair. Successful tissue repair, therefore, not only relies on the host’s ability to mount an effective inflammatory response, but also its ability to finely tune it and limit associated immunopathology.</div?