Assembly and Placement of the Cell Division Ring

? DESCRIPTION (provided by applicant): How cells form specific cell shapes and divide into two during cytokinesis are fundamental questions in cell biology. Mechanical forces, structural elements such as the membranes, cytoskeleton and the extracellular environment, and signaling networks all contribute to specify the shape of the cell. Here, we study mechanical-based regulatory mechanisms for cytokinesis and cell polarization in the fission yeast Schizosaccharomyces pombe. These are simple rod-shaped eukaryotic cells that grow at cell tips and divide medially using a contractile ring and septum. Preliminary results suggest that mechanical forces from the actomyosin contractile ring contribute to shaping the ring and septum cell wall, ensuring that cytokinesis completes efficiently. Mechanical mechanisms also shape the rounded cell ends and contribute to cell polarity. Through quantitative cell biology and molecular genetics, we will elucidate these mechanoregulatory mechanisms and characterize key regulatory components in these pathways. These studies have broad impact on understanding mechanical-based regulation and cell shape control in mammalian cells and are relevant to human diseases such as cancer and heart disease. Our specific aims are 1) to determine to role of the contractile ring in coordinating formation of the septum; 2) to determine how the dynamics and distribution of actin and other ring components are regulated in the contractile ring; 3) to determine how mechanical-based mechanisms regulate cell shape and polarity pathways at the ends of the cell.