Despite operating on grossly different spatial and temporal scales, wound repair at both the single cell and multicellular level are critical for survival and use ancient and conserved processes. Thus, an understanding of the mechanisms underlying both types of repair is of both clinical significance and a model for exploring fundamental cell biological properties. The general aim of this proposal is to understand the molecular and mechanical basis for wound repair in the context of a living organism. Drosophila provides an excellent model for in vivo investigation of wound repair because of its amenability to live imaging, as well as providing genetic tractability unavailable in other wound repair models. We have recently developed an in vivo single cell repair model using the syncytial Drosophila embryo to complement the established multicellular repair model, allowing for exploration of both repair processes in similar genetic backgrounds by altering the developmental timing. Our long-term goal is to delineate the components/machineries, signals, and events that govern these two different repair processes.
The specific aims of this proposal are 1) to investigate the mechanisms associated with the interaction(s) between the membrane and the underlying actomyosin ring during single cell wound repair; 2) to identify and analyze early acting components/signals governing single cell wound repair; and 3) to determine the nature of the coordinated regulation governing the two mechanisms functioning during embryo epithelial repair. Our studies will be of fundamental medical relevance, not only to the numerous diseases associated with recurrent and chronic wounding, but also to generally enhancing the repair response (i.e., enhancing repair speed or prevention of excessive scar tissue formation) and providing the structural and mechanical understanding necessary for tissue engineering central to reconstructing tissues. Our findings will also have broader implications as these repair processes share similar features to normal morphogenetic movements and developmental events.
Wounds occur in response to daily wear and tear, accidents/trauma, violence, and clinical interventions, as well as to medical conditions ranging from infections to diseases and cancers. These injuries happen at many levels, including single cells (i.e., muscle cells) and multicellular tissues (i.e., the skin), and must be rapidly repairedto prevent infection and restore normal function. The aim of this research is to identify the molecules, signals, and regulatory pathways governing wound repair responses in order to develop new strategies for treating cell, tissue, and/or organ damage, as well as to guide new technologies such as tissue engineering.
| Nakamura, Mitsutoshi; Dominguez, Andrew N M; Decker, Jacob R et al. (2018) Into the breach: how cells cope with wounds. Open Biol 8: |
| Nakamura, Mitsutoshi; Verboon, Jeffrey M; Parkhurst, Susan M (2017) Prepatterning by RhoGEFs governs Rho GTPase spatiotemporal dynamics during wound repair. J Cell Biol 216:3959-3969 |
