Paul Martin
paul.martin@bristol.ac.uk
Professor of Cell Biology / Head of Tissue Repair and Morphogenesis Lab
+44 (0) 117 331 2298
Research
Introduction
Embryos heal wounds very rapidly and efficiently and without leaving a scar. They appear to do this using a very similar portfolio of cellular tools to those used by embyos to undergo the natural morphogenetic movements of development. We hope that studying these parallels will help us better understand embryonic tissue movements and also suggest ways in which we might make adult tissues repair more efficiently. Using live confocal imaging of transgenic Drosophila embryos expressing gfp-actin in epithelial tissues we have compared repair of laser-generated epithelial wounds with the paradigm morphogenetic process of dorsal closure and show that remarkably similar actin-based actin machineries (an actomyosin pursestring and dynamic filopodia and lamellipodia) drive these two processes. It seems that very similar mechanisms may also be used by vertebrate embryos to zipper epithelial seams together, for example as the eyelids fuse during foetal development.
Scanning electron microscope view of a wound in a zebrafish larvae showing how contraction of the leading epithelial cells causes the wound margin to “scrunch-up” as it is drawn forward by the action of the actomyosin pursestring.
We have also become interested in the inflammatory response that is an inevitable consequence of any repair response in adult tissues. Our experiments in embryonic chicks and mice (where there is no inflammatory response), and in the neonatal PU.1 null mouse, which is genetically lacking the key leukocyte lineages, suggest that an inflammatory response is not essential for repair and may indeed be causal of fibrosis in post-embryonic animals. Consequently, we have used a microarray approach with this mouse in order to identify a portfolio of candidate inflammation/fibrosis genes and have begun to knock down each of these genes in turn to discover whether this might improve repair. We have also established models of inflammation in the Drosophila embryo and in the translucent zebrafish larval tail fin, which allow us to make DIC movies of the inflammatory response and to dissect the genetics of inflammation, including the precise roles of each of the small GTPases and their effectors in recruitment of inflammatory cells to the wound site.
Link to our main research pages
Group Members
- Yi Feng
Post-doc - using zebrafish to live image the wound inflammatory response - Debi Ford
Technician - microscopy and histology wiz but only comes in one day a week - Becky Jones
Graduate student - modelling of Wiskott Aldrich Syndrome in a zebrafish mutant of WASp - Yutaka Matsubayashi
Research Associate - Investigating concerted epithelial cell migrations in both in vitro and in vivo wound closure - Eva Polk
Graduate student - studies of polycomb regulation during wound healing - Severina Moreira
Graduate Student - dissecting the “damage” chemotactic cues for inflammatory cells in a Drosophila model of wound healing
Selected Publications
- Shaw, T. and Martin, P. (2009)
Epigenetic reprogramming during murine wound healing: loss of polycomb-mediated silencing may enable repair gene upregulation.
EMBO R. 10, 881-886. - Stramer, B. Winfield, M., Shaw, T., Millard, T., Woolner, S. and Martin, P. (2008)
Gene induction following wounding of wild type versus macrophage-deficient Drosophila embryos.
EMBO R. 9, 465-471. - Cvejic, A., Hall, C., Bak-Maier, Flores, MV., Crosier, P., M, Redd. M. and Martin, P. (2008)
Live imaging and genetic dissection of WASp function during the in vivo wound inflammatory response of Zebrafish larvae.
J. Cell Sci. 121, 3196-3206. - Mori, R., Shaw, T. and Martin, P. (2008)
Molecular mechanisms linking wound inflammation and fibrosis – knockdown of osteopontin leads to rapid repair with reduced scarring.
J. Exp Med. 205, 43-51. - Millard, T. and Martin, P. (2008)
Dynamic analysis of filopodial interactions during the zippering phase of Drosophila dorsal closure.
Development 135, 621-626.