Biophysics of Nuclear Condensates

生物体是由具有不同身份的细胞组成的，这些身份由每个细胞中活跃的一组特定基因以及这些基因产生的RNA和蛋白质分子的功能所决定。一个细胞的身份决定了它如何与其他细胞相互作用，以实现复杂的生理功能。这个项目的中心目标是促进发现控制细胞状态的原理。这些原理也可以揭示基因表达的错误调控是如何导致细胞功能失调和患病的。这一知识可以为未来新的干预措施奠定基础，以治疗困扰数百万人的疾病。该项目旨在通过由具有互补专业知识的分子生物学家和物理科学家组成的团队开展的合作研究、教育和推广活动来实现其目标。参与该项目的学生和博士后将学习如何有效地整合生命科学和物理科学，并在令人兴奋的科学前沿发展成为领导者。值得注意的是，该项目与北卡罗来纳中央大学（一所历史上的黑人大学）合作，旨在激励不同的年轻学生追求科学事业。提出的工作的总体目标是推导出描述随机非平衡集体过程如何决定细胞核中控制基因调控和基因组结构的活动的时空模式的一般原理，从而产生细胞状态。蛋白质和RNA的相分离凝聚物在特定的基因组位点形成，本项目旨在确定非平衡过程如何调节它们的形成和功能。DNA环包含活性基因及其调控元件，基因组的活性区和沉默区是分离的。该项目旨在促进对DNA、RNA和蛋白质之间的相互作用如何支撑基因组结构、动力学和功能的理解。该项目由生物科学理事会分子与细胞生物科学部的遗传机制项目和数学与物理科学理事会物理部的生命系统物理学项目共同资助。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。

Organisms are composed of cells with distinct identities defined by the specific set of genes that are active in each cell, and the functions of the RNA and protein molecules that are produced by those genes. A cell’s identity determines how it interacts with other cells to enable complex physiological functions. The central goal of this project is to advance discovery of the principles that control cell state. These principles could also shed new light on how mis-regulation of gene expression causes cells to malfunction and become diseased. This knowledge could lay the foundation for future novel interventions in disorders afflicting millions of people. The project aims to achieve its goal by collaborative research, education, and outreach activities carried out by a team of molecular biologists and physical scientists with complementary expertise. The students and postdoctoral fellows working on the project will learn how to integrate the life and physical sciences fruitfully and develop as leaders in an exciting frontier of science. Notably, in partnership with North Carolina Central University (a historically black college), the project aims to inspire diverse young students to pursue careers in science.The overarching goal of the proposed work is to deduce general principles that describe how stochastic non-equilibrium collective processes determine the spatiotemporal patterns of activity in the nucleus that control gene regulation and genome architecture, and thus the emergence of cell state. Phase-separated condensates of proteins and RNA form at particular genomic loci, and this project aims to determine how non-equilibrium processes regulate their formation and function. DNA loops encompass active genes and their regulatory elements, and active and silent regions of the genome are segregated. The project aims to advance understanding of how interactions among DNA, RNA and proteins underpin genome architecture, dynamics and function.This project is jointly funded by the Genetic Mechanisms program of the Molecular and Cellular Biosciences Division in the Biological Sciences Directorate and the Physics of Living Systems program of the Physics Division in the Mathematical and Physical Sciences Directorate.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.