Physiological and environmental control of C. elegans germline stem cell mitosis

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Mitosis is a highly dynamic process, carefully orchestrated to ensure equal partitioning of the replicated genome between daughter cells. While there are a wealth of mechanistic studies of mitosis in cell culture models, far less is known about how mitosis occurs in cells dividing in situ, i.e. in their native environment, within a living organism. In particular, how mitosis is adapted to different physiological or environmental conditions is largely unknown. This knowledge gap is due primarily to the technological challenge of conducting live imaging studies, which have anchored our current understanding of mitotic processes, on cells dividing in situ. My research program will address this gap by using in situ live cell imaging of mitotic C. elegans germline stem cells (GSCs) to determine how changes at the environmental and organismal level impact mitosis in individual cells. During my postdoctoral fellowship, I developed the first method to live image mitosis in situ in C. elegans adult germline stem cells (GSCs), establishing GSCs as a model for the study of mitosis and affording the unique opportunity to assess how manipulation of environmental conditions and organismal physiology affects the cell biology of mitosis. I have shown that modulating dietary intake or Insulin signaling influences the duration and, likely, the fidelity, of a core mitotic process called “congression”. Following on these results, this research program will combine high-resolution live-cell imaging, quantitative image analysis and genetic approaches to investigate (1) the molecular basis for altered GSC congression under different physiological conditions and (2) the signaling mechanism(s) by which these changes are regulated. The overarching goal of our research program is to discover how mitosis occurs in the physiologically complex environment of a living organism, how it is adapted to preserve fidelity and where mitotic processes are prone to fail under a range of physiological conditions. As most C. elegans genes perform evolutionarily conserved functions, these results may provide insight into the in vivo regulation of mitosis in other organisms and uncover selective pressures that have driven mitotic adaptations.