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

裂殖酵母细胞大小的双边 BBSRC-NSF/BIO 调节

• 批准号: 1548264
• 负责人: Fred Chang
• 金额: $ 70.02万
• 依托单位: Columbia University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1548264&HistoricalAwards=false
• 关键词: Bilateral; BBSRC; NSF; BIO; Regulation

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.

细胞如何控制细胞大小一直是生物学中一个很有兴趣的问题。 虽然与该过程相关的各个组件是已知的，但尚未完全实现将它们集成到合理的功能系统中。在这个合作项目中，来自美国（哥伦比亚大学）和英国（约翰英尼斯研究所）的研究人员将联合收割机实验和理论结合起来，以解决精确控制裂变酵母细胞大小的问题。 初步的理论模型和实验已经允许一个新的假设框架的作用，一个特定的蛋白质，称为Cdr 2，在这个过程中。细胞大小和细胞分裂的控制在所有生物体中都是必要的，了解细胞大小控制的基本动力学提供了新的知识和对细胞大小控制受损的疾病的见解。该项目提供了物理学（包括理论），定量实验方法和细胞生物学之间的接口跨学科培训机会。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，这是该项目的目标。具体重点是Cdr 2，这是一种外周膜结合蛋白，特异性靶向细胞中间的节点区域。这个区域的种群向其他蛋白质“报告”细胞大小的状态，从而促使细胞分裂。 该项目将研究一种新的假设，该假设预测当Cdr 2在节点区域达到一定的阈值浓度时，未结合的Cdr 2可用于抑制下游调节因子Wee 1激酶。在缺乏游离Cdr 2的情况下，Wee 1抑制细胞周期控制因子Cdk 1/Cyclin B以阻断进入有丝分裂。因此，Cdr 2对Wee 1的抑制触发了有丝分裂的进入。这个美国/英国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。