Academic Interest
Roles of cytoskeletal and signaling proteins in cell division and cellular wound healing.

Research Description
The long-term goal of our laboratory is to understand the roles of cytoskeletal and signaling proteins in cell division and cellular wound healing. In the near term, we are focusing on the molecular mechanisms of cytokinesis and single cell wound healing in the fission yeast S. pombe. Cytokinesis partitions cellular constituents into two daughter cells at the end of the cell cycle. When coordinated with the generation of cellular asymmetry, cytokinesis can produce diverse cell types in multicellular organisms. Thus, cytokinesis plays a crucial role in both cell proliferation and cell differentiation. Cytokinesis failure often leads to tetraploid cells, which could become aneuploid and eventually develop into cancer cells. Understanding the mechanism of wound healing is obviously fundamental to human health because wounds can result from diverse sources: trauma, surgery, infection, and muscle contraction. In addition, wounding can promote tumor formation and metastasis, and tumor cells could survive chemotherapy and radiation therapy using wound-healing pathways. Therefore, new therapies could eventually be designed to facilitate wound healing, lessen the incidence of tumorigenesis, and manage tumor cells based on our conceptual breakthroughs on the molecular links between cytokinesis and single-cell wound-healing responses.

The fission yeast S. pombe has emerged as a favorite model system for the analysis of cytokinesis. Not only is it genetically tractable and favorable for microscopic analysis, but it also has highly efficient homologous recombination, a small (13.8 Mb) and fully sequenced eukaryotic genome, and perhaps most importantly, it carries out cytokinesis much like animal cells. The majority of proteins involved in cytokinesis are evolutionarily conserved and thus much of what we learn about these proteins in fission yeast is applicable to human cells.

Contractile rings consisting of actin filaments and myosin-II motor proteins are the common machinery for cytokinesis and other processes including erythrocyte enucleation, morphogenetic epithelial closure, epithelial wound healing, and apoptotic cell extrusion.  It would seem that the ancient cytokinetic contractile ring has been evolutionarily adapted for a variety of cellular functions. Thus, we are studying contractile-ring assembly, constriction, and function in cytokinesis and single cell wound healing using a combination of cellular, molecular, biochemical, genetic, microscopic, and mathematical approaches.

To learn more about our research and publications, please visit our lab website at:
http://biosci.osu.edu/~nile/index.html