Minority Postdoctoral Research Fellowship for FY2006

本项目为2006年度少数民族博士后科研资助项目。细胞分裂是所有生物生长和增殖的基本过程。这需要精确的复制和基因组从母细胞到子细胞的忠实分布。为此，环状内聚蛋白复合体物理连接姐妹染色单体，以防止它们在细胞分裂过程中过早分离。然而，尽管它在染色体稳定性中很重要，但人们对内聚蛋白与染色体的相互作用知之甚少。先前的实验室研究结果表明，黏结蛋白从其最初的结合位点重新定位，并在沿酿酒酵母染色体的聚合转录终止位点积累。为了阐明黏结蛋白与染色体结合的本质，在伦敦研究所Uhlmann Frank博士的指导下，该项目将研究黏结蛋白在体内重新定位的机制。具体来说，本研究将a)表征转录诱导时粘聚蛋白的易位，b)评估着丝粒呼吸过程中粘聚蛋白的行为。该分析将测试黏结蛋白的重新定位是通过沿染色体滑动还是通过复合物在初始结合位点的下游重新加载而发生的。由于内聚蛋白在细胞分裂过程中介导姐妹染色单体内聚是必不可少的，这些发现将为真核生物染色体分离的关键成分的作用机制提供新的见解。我的博士后项目建立在我对基因组维护的浓厚兴趣和背景之上，并将其扩展到对染色体稳定性所涉及的分子机制的理解。我将获得分子遗传学和细胞生物学的互补技能，我将获得利用芽殖酵母（Saccharomyces cerevisiae）作为模型生物来研究基本真核细胞过程的经验。我坚定地致力于追求独立的研究事业，这将使我能够促进科学的多样性，并为学生，特别是来自代表性不足群体的年轻科学家提供导师和榜样。

This project is awarded under the Minority Postdoctoral Research Fellowships and Supporting Activities Program for 2006. Cell division is a fundamental process in the growth and proliferation of all living organisms. This entails the accurate duplication and the faithful distribution of the genome from the mother cell to the daughter cells. For this purpose, the ring-like cohesin complex physically links sister chromatids to prevent their premature separation during cell division. However, despite its importance in chromosomal stability, little is known about the interaction of cohesin with chromosomes. Previous laboratory findings have revealed that cohesin relocates from its initial binding sites and accumulates at sites of convergent transcriptional termination along Saccharomyces cerevisiae chromosomes. To elucidate the nature of cohesin binding to chromosomes, this project, under the mentorship of Dr. Uhlmann Frank at the London Research Institute, will investigate the mechanism of cohesin relocation in vivo. Specifically, this study will a) characterize the translocation of cohesin upon induction of transcription and b) assess the behavior of cohesin during centromere breathing. This analysis will test whether cohesin relocation occurs by sliding along chromosomes or by reloading of the complex downstream of the initial binding site. Since cohesin is essential for mediating sister chromatid cohesion during cell division, these findings will provide novel insights about the mechanism of action of a critical component of eukaryotic chromosome segregation. My postdoctoral project builds on my strong interest and background in genomic maintenance and extends it toward an understanding of the molecular mechanisms involved in chromosome stability. I will acquire complementary skills in molecular genetics and cell biology, and I will gain experience in utilizing budding yeast, Saccharomyces cerevisiae, as a model organism for examining fundamental eukaryotic cellular processes. I am firmly committed to pursuing an independent research career, which will enable me to promote diversity in science and to serve as a mentor and role model for students, especially young scientists from underrepresented groups.