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

细胞如何控制细胞的大小仍然是生物学中非常感兴趣的问题。虽然与这一过程相关的各个组件是已知的，但它们集成到一个合理的功能系统中还没有完全实现。在这个合作项目中，来自美国(哥伦比亚大学)和英国(John Innes Institute)的研究人员将实验和理论相结合，以解决分裂酵母细胞大小的精确控制问题。初步的理论模型和实验已经允许提出一种关于特定蛋白质在这一过程中的作用的新假说，称为CDR2。控制细胞大小和细胞分裂在所有活着的生物体中都是必要的，了解细胞大小控制的基本动态既提供了新的知识，也提供了对细胞大小控制受损的疾病的见解。该项目在物理学(包括理论)、定量实验方法和细胞生物学之间提供了跨学科的培训机会。要了解调节细胞大小和细胞分裂的机制需要理论和实验的整合，这是本项目的目标之一。具体的焦点是Cdr2，它是一种外周膜结合蛋白，专门针对细胞中部的结节区域。该区域的种群向其他促使细胞分裂的蛋白质“报告”细胞大小的状态。这个项目将检验一个新的假说，该假说预测当Cdr2在节点区域达到一定的阈值浓度时，未结合的Cdr2可以抑制下游调节因子Wee1激酶。在没有游离Cdr2的情况下，Wee1抑制细胞周期控制因子CDK1/Cyclin B，以阻止进入有丝分裂。因此，Cdr2对Wee1的抑制触发了有丝分裂的进入。这一美英合作项目得到了美国国家科学基金会和英国生物技术和生物科学研究理事会的支持。

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.