Bilateral NSF/BIO-BBSRC: Regulation of cell size in fission yeast

双边 NSF/BIO-BBSRC：裂殖酵母细胞大小的调节

• 批准号: BB/M023796/1
• 负责人: Martin Howard
• 金额: $ 47.09万
• 依托单位: John Innes Centre
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM023796%2F1
• 关键词: Bilateral; NSF; BIO; BBSRC; Regulation

How is the size of a cell controlled? Cells come in vastly different sizes, ranging from tiny bacteria to very large neurons or protozoa, but cells of a given cell type generally display a fairly constant size. The size of cells is important for their function and livelihood, and is tightly regulated. In general, how cell size is specified by molecular components remains, however, mysterious. Are there rulers that allow the cell to determine how big it is? In actively dividing cells, growth is coordinated with cell division so that cell size is maintained. One strategy is for cells to sense that they are big enough before undergoing a cell division. Although such controls have been proposed for decades, the mechanisms for cell size sensing are still not properly understood in any cell type, not even in simpler cases such as bacteria and yeast. We propose to study the fundamentals of cell size control in a simple model cell type, the fission yeast. These cells are ideally suited for this purpose because of their simple shape and regular division habits. The internal machinery that regulates cell division is conserved up to humans, making the findings in these simple cells generally relevant. Decades of research have identified the key molecules needed for cell size regulation. However, the central question of how these molecules are used to sense cell size remains poorly understood. We have recently suggested a new mechanism for how one of these molecules, Cdr2, is used to sense the size of the cell. We propose that Cdr2 probes the surface area of the cell, and then accumulates in dot-like structures in the middle of the cell called "nodes". From these nodes, Cdr2 can then report on the status of cell size to other proteins that tell the cell to divide. In this proposal we will study how Cdr2 senses cell size and how it reports to the cell cycle machinery. This effort involves collaboration between experts in mathematical modelling and experimentalists who will be imaging fluorescently labelled proteins inside living yeast cells. Our results will reveal how the rapid movements of Cdr2 and other molecules from one place to another in the cell allow it to sense cell size. The importance of this work is that it will provide one of the first examples of a cell size sensing mechanism. This will have broad implications into how other cells control their sizes, and ultimately provide insight into diseases such as cancer where cell size controls are altered.

单元格的大小是如何控制的？细胞的大小差异很大，从微小的细菌到非常大的神经元或原生动物，但给定细胞类型的细胞通常表现出相当恒定的大小。细胞的大小对于它们的功能和生存很重要，并且受到严格的调控。然而，总的来说，分子成分如何决定细胞大小仍然是个谜。是否有标尺可以让单元格确定其大小？在活跃分裂的细胞中，生长与细胞分裂协调一致，从而维持细胞大小。一种策略是让细胞在进行细胞分裂之前感知到它们足够大。尽管这种控制方法已经提出了几十年，但在任何细胞类型中，细胞大小传感的机制仍然没有被正确理解，甚至在细菌和酵母等更简单的情况下也是如此。我们建议研究一种简单的模型细胞类型——裂殖酵母中细胞大小控制的基础原理。这些细胞由于其简单的形状和规则的分裂习惯而非常适合此目的。调节细胞分裂的内部机制对于人类来说是保守的，这使得这些简单细胞中的发现具有普遍意义。数十年的研究已经确定了细胞大小调节所需的关键分子。然而，如何使用这些分子来感知细胞大小的核心问题仍然知之甚少。我们最近提出了一种新机制，如何使用这些分子之一 Cdr2 来感知细胞的大小。我们提出 Cdr2 探测细胞的表面积，然后在细胞中间的点状结构中积累，称为“节点”。然后，Cdr2 可以从这些节点向其他蛋白质报告细胞大小的状态，从而告诉细胞进行分裂。在本提案中，我们将研究 Cdr2 如何感知细胞大小以及它如何向细胞周期机制报告。这项工作涉及数学建模专家和实验人员之间的合作，他们将对活酵母细胞内的荧光标记蛋白质进行成像。我们的结果将揭示 Cdr2 和其他分子从细胞中的一个位置到另一个位置的快速移动如何使其能够感知细胞大小。这项工作的重要性在于它将提供细胞大小传感机制的第一个例子。这将对其他细胞如何控制其大小产生广泛的影响，并最终提供对细胞大小控制发生改变的癌症等疾病的深入了解。

项目成果

Controlling cell size through sizer mechanisms.

• DOI: 10.1016/j.coisb.2017.08.010
• 发表时间: 2017-10-01
• 期刊: Current opinion in systems biology
• 影响因子: 3.7
• 作者: Facchetti, Giuseppe;Chang, Fred;Howard, Martin
• 通讯作者: Howard, Martin

Reprogramming Cdr2-Dependent Geometry-Based Cell Size Control in Fission Yeast

• DOI: 10.1016/j.cub.2018.12.017
• 发表时间: 2019-01-21
• 期刊: CURRENT BIOLOGY
• 影响因子: 9.2
• 作者: Facchetti, Giuseppe;Knapp, Benjamin;Howard, Martin
• 通讯作者: Howard, Martin