RUI: Cell Size and Molecular Concentrations in eukaryotes

Every cell type has a characteristic size that is essential for proper function. Cells grow to a determined size and then either divide or stop growing. However, it remains unclear how cells “know” and regulate their size, and how size influences cell behavior. This NSF-funded project will uncover the mechanisms by which cells sense and respond to changes in size, using the budding yeast Saccharomyces cerevisiae as a model system. Our research focuses on the role of specific signaling proteins (Protein Kinase C and MAP kinase) to understand how they control cell size and adjust cellular processes. To address these questions, we will combine advanced imaging tools with genome-wide analyses to identify key proteins involved in cell size regulation and to understand how size changes impact cell physiology. This project will provide hands-on research opportunities for undergraduate students at Brooklyn College, a public university in New York City. This study will probe the molecular mechanisms that regulate cell size in S. cerevisiae to: 1) identify cell signaling pathway(s) that detects changes in cell size; 2) use genetically encoded multimeric nanoparticles combined with imaging and data analysis to define mechanisms of cytoplasmic and nuclear dilution in growing cells; and 3) utilize high-throughput single-cell transcriptomics to understand the molecular underpinnings of cell size regulation. The project focuses on Protein Kinase C (PKC) and Mitogen-activated protein kinases (MAPKs) to elucidate how cells perceive their size and activate PKC-MAPK signaling pathways to “decide” their subsequent behavior. Broader Impacts of this proposal include: 1) the potential to significantly advance our knowledge of cell size control across eukaryotes; 2) provide research opportunities for undergraduates and a head start with lab experience and scientific research; and 3) establish a 'systematic curriculum' integrated into upper-level Biology courses designed to increase the number of students engaged in STEM. 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.