Collaborative Research: Regulation of Nuclear Size

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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.