Research groups

Research

Studies of wound healing and inflammation in flies and fish and mice.

Embryos heal wounds very rapidly and efficiently and without leaving a scar. Studying how they do this can tell us much about the natural morphogenetic movements of embryogenesis as well as suggesting 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 revealed the key actin machineries that drive the paradigm morphogenetic process of dorsal closure which appears to bear striking analogy with re-epithelialisation of a vertebrate skin wound. Using embryos expressing mutant forms of the various small GTPases, we have tested the function of each of these actin-based elements - the actin cable and dynamic filopodia and lamellipodia – in both dorsal closure and the repair of laser-generated wound holes in the fly embryo. Our experiments in embryonic chicks and mice and in the neonatal PU.1 null mouse, which is genetically macrophageless, suggest that an inflammatory response is not essential for healing 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 whose functions we are now testing by in vivo knockdown of antisense ODNs. Finally, by taking advantage of the translucency of Drosophila embryos and the zebrafish larval tail we have we are using these two models to make DIC movies of the inflammatory response and to dissect the genetics of this process by screening for mutants that fail to recruit leukocytes to the wound site and by knockdown of candidate “inflammation” genes. Our hope is that these basic cell and molecular studies in genetically tractable organisms will supply us with the clues we need to design the new repair and regeneration medicines of the future. Research projects are available in all of these areas.

Wound healing (C,D) recapitulates morphogenesis(A,B) in the Drosophila embryo

Group

Yutaka Matsubayashi, Yi Feng, Severeina Moreira, Eva Polk, Becky Jones and Debi Ford.

Recent publications

Shaw T, and Martin P. (2009). Epigenetic reprogramming during wound healing: loss of polycomb-mediated silencing may enable upregulation of repair genes. EMBO Rep. 10(8), 881-886.

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.

Cvejic, A. Hall, C. Bak-Maier, M. Flores, MV. Crosier, P. Redd, MJ. and Martin, P. (2008). Analysis of WASp function during the wound inflammatory response--live-imaging studies in zebrafish larvae. J Cell Sci. 121, 3196-3206.