Light-Induced Chromosomal InteracKon: A New Tool to Study Chromosome Dynamics and Its Biological Roles

该项目将开发一种新的方法，利用光来控制和操纵染色体的3D构象。染色体包含有机体的遗传物质，在许多细胞过程中发挥着重要的作用。为了执行这些功能，染色体通常需要物理上的相互作用。尽管已经发现了染色体之间的许多相互作用，但这种相互作用能以多快的速度建立起来还不清楚。该项目将提供一种方法来探索这种动态，并了解这些动态是如何受到监管的。这个项目将吸引本科生和研究生从事跨学科的研究，将遗传学、成像学和计算生物学联系起来。主要研究人员正在开发一门跨学科的生物物理学课程，该项目的一些结果将被纳入该课程的两个新的教学模块。该项目还将允许首席研究人员继续推动来自多个学科的女性和少数族裔学生从事科学研究。该项目将设计面包师的酵母细胞，以便将光诱导的二聚化蛋白招募到目标染色体基因座，然后使用光来诱导两个基因座之间的物理相互作用。该实验室将收集两个染色体基因座相遇并在二聚化逆转时解离所需时间的定量测量。接下来，他们将研究细胞周期的不同阶段、细胞大小和DNA损伤如何影响相遇时间。该项目还将探索这种诱导相互作用如何影响全基因组染色体构象。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 will develop a novel method to use light to control and manipulate the 3D conformation of chromosomes. Containing the genetic materials of an organism, chromosomes play essential roles in many cellular processes. To perform these functions, chromosomes often need to interact physically. Although many interactions between chromosomes have been found, how fast such interactions can be established is not clear. The project will provide a method to probe such dynamics and understand how these dynamics are regulated. This project will engage undergraduate and graduate students in interdisciplinary research bridging genetics, imaging, and computational biology. The principle investigator is developing an interdisciplinary biophysics course, and some of the results from this project will be incorporated into two new teaching modules in that course. This project will also allow the principle investigator to continue promoting women and minority students from multiple disciplines to pursue science.The project will engineer baker’s yeast cells in order to recruit light-induced dimerization proteins to targeted chromosome loci and then use light to induce physical interactions between the two loci. The lab will collect quantitative measurements of the time it takes the two chromosomal loci to encounter one another and to dissociate when dimerization is reversed. Next, they will examine how the phases of the cell cycle, cell size, and DNA damage affect the encounter time. The project will also probe how such induced interactions affect genome-wide chromosome conformation.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.