Collaborative Research: Regulation of Nuclear Size

这个项目阐明了细胞中细胞核的大小是如何确定的。一百多年来，人们一直认识到，核的大小随着细胞的大小而增大，因此更大的细胞有更大的核。随着细胞的生长，细胞核的生长速度也是一样的。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知之甚少。破译这些机制将使人们深入了解为什么细胞调节核大小是重要的，并将提供如何实现细胞和细胞器大小调节的一般原则。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更广泛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，将开发一个核尺寸定标的定量模型。这个模型提出，核的大小由渗透压和膜张力等物理因素决定。具体地说，核的大小主要由核质和细胞质内胶体渗透压的平衡决定，而胶体渗透压是由每个隔室中存在的渗透活性大分子的数量决定的。一般的方法是采用理论建模和定量实验相结合的方法，以裂殖酵母为模式生物。在S.pombe中，细胞核扮演着“理想的渗透率计”的角色，其大小与其渗透环境的大小相对应。该模型将在渗透压等物理参数变化的实验中进行测试。核大小恒定的机制将被阐明，在这个机制中，异常的核大小逐渐得到纠正。我们将研究核体积增长和核包膜表面积之间的耦合机制。这种核大小的渗透模型承诺将极大地影响对细胞器大小调节的一般理解。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.