Bilateral BBSRC-NSF/ BIO Regulation of Cell Size in Fission Yeast

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How cells control cell size remains a question of great interest in biology. Although individual components related to this process are known, their integration into a rational functional system has not been fully achieved. In this collaborative project, investigators from the US (Columbia University) and the UK (John Innes Institute) combine experiments and theory to address the precise control of fission yeast cell size. The preliminary theoretical model and experimentation has allowed the framing of a novel hypothesis on the role of a specific protein, termed Cdr2, in this process. Control of cell size and cell division is necessary in all living organisms, and understanding the basic dynamics of cell size control offers both new knowledge and insight into diseases where cell size control is impaired. The project provides interdisciplinary training opportunities at the interface between physics (including theory), quantitative experimental methods and cell biology.To understand the machinery that regulates cell size and cell division requires the integration of theory and experiment, which is a goal of this project. The specific focus is on Cdr2, which is a peripheral membrane binding protein that specifically targets the node area in the middle of the cell. The population of this area "reports" the status of cell size to other proteins that prompt the cell to divide. This project will examine a novel hypothesis that predicts that when Cdr2 reaches a certain threshold concentration at the node region, unbound Cdr2 becomes available to inhibit the downstream regulatory factor, Wee1 kinase. In the absence of free Cdr2, Wee1 inhibits the cell cycle control factors Cdk1/Cyclin B to block entry into mitosis. Thus the inhibition of Wee1 by Cdr2 triggers the entry into mitosis.This collaborative US/UK project is supported by the US National Science Foundation and the UK Biotechnology and Biological Sciences Research Council.