Determining how cell growth triggers cell division

PROJECT SUMMARY The overarching goal of this project is to understand how cell growth triggers cell division in budding yeast and identify general regulatory principles applicable to eukaryotic cells. Our work aims to understand how the most basic aspect of cell morphology, cell size, is controlled. Solving this question has the potential to revolutionize our understanding of how cell division is regulated in both natural developmental contexts and in disease. In 2015, my laboratory reported a breakthrough discovery in understanding how growth triggers division in budding yeast. While it was expected that growth would act to increase the activities of the cyclin-dependent kinases (Cdk) known to promote cell division, this is not the case. Rather, we found that cell growth acts in the opposite manner. Cell growth triggers division by diluting a protein that inhibits cell division, Whi5. This discovery formed the basis of my first MIRA grant, which funded important progress in understanding G1/S cell cycle control, cell size control, and its relationship to cellular senescence in both budding yeast and human cells. This MIRA project builds on our prior discoveries by deepening our understanding of how budding yeast regulate the size. More specifically, the project defines three new research directions: 1) Investigating the molecular mechanism behind the size-independent transcription of WHI5, focusing on the role of forkhead transcription factors. 2) Identifying Whi5-independent mechanisms that regulate cell size at the G1/S transition and defining the role of the SBF transcription factor in this process. 3) Studying the role of Bck2 in the G1/S transition and its interaction with the SBF transcription factor to understand its influence on cell size control. These directions aim to uncover novel insights into the cellular machinery regulating cell size, which has broader implications for eukaryotic cell biology and medical research.