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.
