Collaborative Research: Regulation of Nuclear Size

这个项目阐明了细胞核的大小是如何确定的。一百多年来，人们一直认识到细胞核的大小与细胞的大小有关，因此较大的细胞有较大的细胞核。随着细胞的生长，细胞核也以同样的速度生长。这种尺寸缩放关系是生命的基本规则之一，但负责核尺寸调节的机制仍然知之甚少。破译这些机制将有助于了解细胞调节细胞核大小的重要性，并提供细胞和细胞器大小调节是如何完成的一般原理。总的来说，这项工作将增加我们对用于构建活细胞的基本细胞过程的了解。作为一个更广泛的成果，该项目将通过开发教育模块和科学展览，向更大的公众介绍物理力量和定量测量在细胞生物学研究中的重要性。在这个项目中，将开发一个核尺寸缩放的定量模型。该模型提出，核的大小是由渗透压和膜张力等物理因素决定的。具体来说，核的大小很大程度上是由核质和细胞质内的胶体渗透压平衡决定的，而胶体渗透压是由每个隔室中存在的具有渗透活性的大分子的数量决定的。一般的方法是用理论建模和定量实验相结合的裂变酵母裂糖酵母pombe作为模式生物。在S. pombe中，细胞核表现为“理想渗透计”，其大小与渗透环境定量对应。该模型将在诸如渗透压等物理参数变化的实验中进行检验。将阐明核尺寸异常逐渐得到纠正的核尺寸稳态机制。耦合核体积增长和核膜表面积的机制将被检查。这种核大小的渗透模型有望极大地影响对细胞器大小调节的一般理解。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This project elucidates how the size of the nucleus in the cell is determined. It has been appreciated for over a hundred years that nuclear size scales with cell size, so that larger cells have larger nuclei. As cells grow, the nucleus grows at the same rate. This size scaling relationship is one of the fundamental rules of life, but the mechanisms responsible for nuclear size regulation are still poorly understood. Deciphering such mechanisms will give insights into why it is important for cells to regulate nuclear size and will provide general principles of how size regulation of cells and organelles is accomplished. In general, this work will add to our knowledge of fundamental cellular processes that are used to build living cells. As a broader outcome, this project will introduce to the larger public the importance of physical forces and quantitative measurements in cell biology research through development of educational modules and a scientific exhibit. In this project, a quantitative model for nuclear size scaling will be developed. This model proposes that nuclear size is specified by physical factors such as osmotic pressure and membrane tension. Specifically, nuclear size may be determined largely by a balance of colloid osmotic pressures within the nucleoplasm and cytoplasm, which are determined by the numbers of osmotically active macromolecules present in each compartment. The general approach is to use theoretical modeling coupled with quantitative experiments on the fission yeast Schizosaccharomyces pombe as a model organism. In S. pombe, the nucleus behaves as an “ideal osmometer” whose size corresponds quantitatively to its osmotic environment. This model will be tested in experiments in which physical parameters such as osmotic pressure are varied. The mechanism of nuclear size homeostasis in which abnormal nuclear sizes are gradually corrected will be elucidated. Mechanisms that couple nuclear volume growth and nuclear envelope surface area will be examined. This osmotic model of nuclear size promises to greatly impact the general understanding of organelle size regulation.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.