Detecting Death and Damage; Understanding Macrophage Migration in vivo
A critical early wound response is the recruitment of inflammatory cells drawn by danger cues released by the damaged tissue. Hydrogen peroxide has been identified as the earliest damage signal in Drosophila and Zebrafish and we have shown using fly embryos that laser wounding triggers an instantaneous calcium flash in the epithelium which in turn activates the NADPH oxidase DUOX to generate Hydrogen Peroxide. As a consequence of hydrogen peroxide production, macrophages within the fly embryo rapidly migrate toward the wound site powered by the formation of dynamic actin-rich lamellipodia. We are using live imaging to understand the mechanism by which inflammatory cells are able to detect hydrogen peroxide and generate the dynamic actin-rich structures necessary for their migration. We are particularly interested in how immune cells are able to prioritise competing cues such as wound induced damage signals and ‘eat me’ cues from apoptotic corpses and how exposure to one of these signals influences the cells ability to respond to subsequent cues.

SPEAKER BIOGRAPHY

Prof Wood is a Wellcome Trust Senior Research Fellow within the Centre of Inflammation Research at the University of Edinburgh. After carrying out his PhD at UCL and Postdoctoral work in Lisbon, Portugal he set up his lab at the University of Bath in 2006 as a Wellcome Trust Career Development Fellow. In 2010 he became a Wellcome Trust Senior Fellow and in 2014 moved his lab to the University of Bristol before moving again to Edinburgh in 2018. Over the past 16 years his lab has played a major part in defining the molecular machinery that drives inflammatory migration of Drosophila macrophages and the way in which the in vivo environment impacts upon the ability of these cells to migrate. One key interest has been to understand the balance between competing cues and how the exposure to one signal can affect the ability of an immune cell to respond to another. In 2016, his lab provided the first demonstration of innate immune memory in Drosophila macrophages, showing that engulfment of an apoptotic corpse transforms macrophages from naïve cells unable to recognise wounds or bacteria into ‘primed’ immune cells able to raise an inflammatory response to wounds or infection (Weavers et al, Cell 2016). His lab was able to show that inflammatory migration requires the complement protein Mcr (Lin et al, Cell 2017) and has also discovered that epithelial cells are also able to ‘remember’ exposure to inflammatory signals following wounding by activating a cytoprotective mechanism within them driving resilience and protecting from further damage (Weavers et al, Current Biology 2019). The Wood lab has discovered that macrophages can readily switch mode of engulfment to overcome immobility and spatial constriction (Davidson and Wood, Cell Reports 2020) and, combining Drosophila and zebrafish wounding studies, has identified Pez/PTPN21 as a novel regulator of inflammation conserved from invertebrates to vertebrates (Campbell, Davidson et al, Current Biology 2021). Additionally, In 2018 work in the lab discovered that Drosophila adipocytes are not immotile, as previously presumed, but actively migrate to wounds using a novel mode of motility (Franz et al, Dev Cell 2018). This work received much attention globally featuring in the New York Times. Most recently the lab has generated a novel probe to identify apoptosis in vivo and used this to reveal that macrophages prioritise eating over digestion to maximise global apoptotic clearance (Raymond, Davidson et al, Science 2022).
Date: 3 March 2023, 13:00 (Friday, 7th week, Hilary 2023)
Venue: Sherrington Building, off Parks Road OX1 3PT
Venue Details: Blakemore Lecture Theatre
Speaker: Will Wood (Centre for Inflammation Research, University of Edinburgh)
Organising department: Department of Physiology, Anatomy and Genetics (DPAG)
Organisers: Dr Mootaz Salman (DPAG, University of Oxford), Dr Armin Lak (DPAG, University of Oxford)
Organiser contact email address: hod-pa@dpag.ox.ac.uk
Host: Professor Paul Riley (DPAG, University of Oxford)
Part of: DPAG Head of Department Seminar Series
Booking required?: Not required
Audience: Members of the University only
Editor: Talitha Smith