Grant: Project Grant

Uncontrolled cell division forms the basis for all cancers. Consequently, most anti-cancer drugs block the cell cycle, with many specifically targeting mitosis (e.g. Taxol). Variable drug efficiency is a major obstacle in the development of robust cancer therapies. It is not known why cancer cell responses vary, but underlying differences in core mitotic processes may contribute. Proper cell division is also vital to maintain the function of many adult tissues, allowing adult stem cells to sustain normal tissue turnover and to promote tissue regeneration following damage. A decline in stem cell function has been linked to a range of age-related pathologies, including organ failure and the development of cancer. A significant gap in our understanding of mitosis derives from the lack of model systems to study cells dividing within their native environment. Consequently, we know very little about how mitosis occurs within specific cell types, within the complex physiological environment of a living organism. Importantly, mitosis in both adult stem cells and tumor cells will be influenced by these in vivo factors. The goal of this proposal is to investigate how mitosis occurs in vivo and to uncover how key aspects of mitotic regulation are affected by cell fate and broader physiological factors. We use a small nematode worm (C. elegans) as a model system, which permits live-imaging studies of mitosis within intact living animals that are challenging in mammalian models and not possible in human subjects. As many C. elegans genes perform conserved functions in humans and several major mitotic proteins were discovered in C. elegans, it is highly likely that the mechanisms uncovered in my lab will be important for mitosis in human cells. Understanding how mitosis occurs in vivo will fill a major gap in our understanding of the cell biology of mitosis and inform the development of new, more effective drugs designed to improve adult stem cell function or to treat cancer.