Regulation of T Lymphocyte mRNA Degradation

描述（由申请人提供）：本研究职业奖申请描述了博士的职业发展计划。Bohjanen进一步发展他的研究计划，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助理教授职位。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降解水平上受调控的T淋巴细胞基因。微阵列技术将用于基于T淋巴细胞的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衰减速率在细胞活化后发生变化的转录物。具体的mRNA转录，其衰减率的调节将进一步确定新的序列元件和反式作用因子，调节mRNA的衰变。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，含有被称为富含AU的元件（战神）的序列，其是mRNA降解的重要调节因子。蛋白质HuA和TTP特异性结合战神，从而调节mRNA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博士发展他的研究计划提供了一个强大的互动知识环境。他与在相关研究领域具有专业知识的同事进行了多次互动，包括T淋巴细胞免疫学，T淋巴细胞的病毒感染以及RNA-蛋白质相互作用的生物化学。他在免疫学中心，微生物学系和RNA生物学社区在大学内的研究会议的参与将提供在他的实验室进行的工作正在进行的关键评估。Bohjanen博士有足够的空间和资源进行拟议的实验，并通过生物医学基因组学中心提供设施进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受保护的研究时间，使他能够建立一个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.