Collaborative Research: Regulation of Nuclear Size

这个项目阐明了细胞核的大小是如何决定的。一百多年来，人们已经认识到，细胞核的大小与细胞大小成比例，因此较大的细胞具有较大的细胞核。随着细胞的生长，细胞核也以同样的速度生长。这种大小比例关系是生命的基本规则之一，但对核大小调节的机制仍然知之甚少。破译这些机制将使我们深入了解为什么细胞调节核大小是重要的，并将提供细胞和细胞器大小调节是如何完成的一般原则。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，向广大公众介绍物理力和定量测量在细胞生物学研究中的重要性。 在这个项目中，将开发一个核尺寸定标的定量模型。该模型提出，核的大小是由物理因素，如渗透压和膜张力。具体地，核大小可以主要由核质和细胞质内的胶体渗透压的平衡决定，其由每个隔室中存在的药理活性大分子的数量决定。一般的方法是使用理论建模加上定量实验的裂殖酵母粟酒裂殖酵母作为模式生物。In S.在粟酒裂殖酵母中，细胞核表现为“理想渗透计”，其大小定量地对应于其渗透环境。该模型将在渗透压等物理参数变化的实验中进行测试。将阐明核大小动态平衡的机制，其中异常的核大小逐渐得到纠正。将研究耦合核体积增长和核膜表面积的机制。核大小的渗透模型有望极大地影响细胞器大小调节的一般理解。该奖项反映了NSF的法定使命，并已被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

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.