The process of dividing one cell into two - termed cytokinesis - is fundamental to all life on Earth and this project seeks to further elucidate the structure and function of the protein-based machinery that mediates the splitting of the cell. The machinery that accomplishes animal cell cytokinesis is known as the contractile ring and it consists of a transiently assembled belt of cytoskeletal proteins which generates the force required to divide the cell. Employing a variety of imaging technologies in combination with computational modeling, this project will test the hypothesis that in animal cells the contractile ring assembles from nodes of contractile proteins that aggregate into a functional contractile assemblage. The resulting increase in knowledge of the architecture and dynamics of the contractile ring derived from this project will have significant impacts on research in the fields of cell proliferation, movement, shape change, as well as differentiation and development. This project will train students from a four-year liberal arts college (Dickinson College) and a minority-serving research university (New Mexico State University), who will work not only at their respective institutions but also collaboratively at the University of Washington's Friday Harbor Laboratories (FHL). A computational modeler with experience in agent-based modeling of cytoskeletal protein dynamics will provide training in agent-based modeling. Lastly, the investigators will engage in a number of activities that will broaden the impact of the project through the broadening of participation of URM students, the integration of research and education, and public engagement and improvement of science literacy.
The aims of this project will test the hypothesis that the contractile ring assembles from nodes comprised of the cytoskeletal proteins myosin II, actin, septins and anillin, which then congress into a mature contractile machine that generates the force necessary for cytokinesis. This node-based mode of ring assembly occurs in fission yeast, but had never been demonstrated in higher order animals cells until the investigators described the presence of node-like structures in the early contractile rings of sea urchin embryos. Using this report as a foundation, the investigators will apply super resolution, electron, and live cell microscopy to examine node composition, assembly and aggregation during cytokinesis in sea urchin and sea star embryos. Using empirical data as well as existing models for yeast node congression, two- and three-dimensional, agent-based models will be tested in silico, and results from these simulations will be used to inform further experimentation. Lastly, these approaches will be applied to the study of polar lobe formation, which uses a contractile ring-like structure that forms during cytokinesis in many early embryos, but whose composition and spatiotemporal regulation may be quite different from a standard contractile ring.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
