Regulation of T Lymphocyte mRNA Degradation

描述（由申请人提供）：这份研究生涯奖申请描述了Paul R. Bohjanen博士的职业发展计划，以进一步发展他的研究项目，旨在了解mRNA降解在调节T淋巴细胞基因表达中的作用。Bohjanen博士最近完成了传染病的临床培训，并于2000年7月开始了他的第一个教员职位，担任助理教授。他提出的研究是基于mRNA降解在调节T淋巴细胞基因表达中起重要作用的假设。第一个具体目标是确定在mRNA降解水平上受调节的T淋巴细胞基因。微阵列技术将用于根据mRNA衰减速率来分析T淋巴细胞中表达的mRNA转录物，并鉴定其mRNA衰减速率随细胞激活而变化的转录物。降解速率受调控的特定mRNA转录本将进一步表征，以确定调控mRNA降解的新序列元件和反式作用因子。T淋巴细胞转录物的一个子集，包括细胞因子转录物和某些原癌基因转录物，包含被称为富au元素（AREs）的序列，这是mRNA降解的重要调节因子。蛋白HuA和TTP与AREs特异性结合，从而调节mRNA的降解。第二个具体目标是表征这些蛋白在T淋巴细胞中的表达和功能。明尼苏达大学为Bohjanen博士提供了一个强大的、互动的智力环境来发展他的研究项目。他与在T淋巴细胞免疫学、T淋巴细胞病毒感染和rna -蛋白相互作用的生物化学等相关研究领域具有专业知识的同事有许多互动。他参加了免疫学中心、微生物系和RNA生物学社区的研究会议，这将为他的实验室工作提供持续的批判性评估。Bohjanen博士有足够的空间和资源来进行拟议的实验，并通过生物医学基因组学中心提供设施来执行拟议的微阵列实验。独立科学家奖将为Bohjanen博士提供额外的支持和保护研究时间，使他能够建立富有成效的研究生涯。

DESCRIPTION (provided by applicant): This Research Career Award application describes a career development plan for Dr. Paul R. Bohjanen to further develop his research program directed toward understanding the role of mRNA degradation in regulating T lymphocyte gene expression. Dr. Bohjanen recently completed clinical training in infectious diseases and started his first faculty position as an Assistant Professor in July of 2000. His proposed research is based on the hypothesis that mRNA degradation plays an important role in regulating T lymphocyte gene expression. The first specific aim is to identify T lymphocyte genes that are regulated at the level of mRNA degradation. Microarray technology will be used to profile mRNA transcripts expressed in T lymphocytes based on their rates of mRNA decay and to identify transcripts whose rate of mRNA decay changes upon cellular activation. Specific mRNA transcripts whose rate of decay is regulated will be characterized further to identify novel sequence elements and trans-acting factors that regulate mRNA decay. A subset of T lymphocyte transcripts, including cytokine transcripts and certain proto-oncogene transcripts, contain sequences known as AU-rich elements (AREs) that are important regulators of mRNA degradation. The proteins HuA and TTP bind specifically to AREs and thereby regulate mRNA degradation. The second specific aim is to characterize the expression and function of these proteins in T lymphocytes. The University of Minnesota provides a strong and interactive intellectual environment for Dr. Bohjanen to develop his research program. He has numerous interactions with colleagues who have expertise in related research areas including T lymphocyte immunology, virus infection of T lymphocytes, and the biochemistry of RNA-protein interactions. His participation in research conferences within the Center for Immunology, Department of Microbiology, and the RNA biology community at the university will provide an ongoing critical evaluation of work performed in his laboratory. Dr. Bohjanen has adequate space and resources for carrying out the proposed experiments, and facilities are available through the Biomedical Genomics Center to perform the proposed microarray experiments. The Independent Scientist Award would provide Dr. Bohjanen with additional support and protected time for research to enable him to establish a productive research career.