T-TYPE CYCLIN/CDK9 COMPLEXES IN T CELL ACTIVATION

描述(改编自应用程序)：此应用程序提出一个计划 以加强泽维尔·格拉纳博士的研究事业。他的目标是实现 在研究生水平的研究和教学方面都表现出色。这个 此应用程序的目标是为应聘者获得薪资支持 五年，允许较长的初等教育时期 专注于研究和相关活动，将他从 增加了医学院的教学和服务负荷。短期内 研究目标是达到他目前资助的 申请包括NIAID的RO1拨款、提交的 续签W.W.史密斯慈善信托基金和NIGMS的R29。 格拉纳博士是一名分子生物学家和生物化学家。格兰纳博士是一名研究人员 在费尔斯学院担任助理教授两年。1996年12月 年，他被提升到目前的终身教职--跟踪助理教授 坦普尔大学医学院生物化学系。一个 提出了职业发展计划，以加强大学的研究计划 候选人。该奖项将允许候选人在研究方面取得进步。 及时掌握各相关领域的能力和专业知识 为了延长他的研究计划，他增加了他的小组的规模 研究生和技术人员。此外，候选人计划 通过参与多项研究和学术技能 与候选人寻求的领域相关的座谈会和讲习班 获得更多专业知识，并通过与多名资深员工互动 坦普尔大学医学院的研究人员。研究计划 本质上是为了满足候选人资助的特定目标 RO1和R29拨款和向W.W.史密斯提交的续签拨款申请 慈善信托基金。合并后的具体目标如下：第一， 阐明导致个体T-型上调的机制 细胞周期蛋白/CDK9复合体在T细胞活化和分化中的作用 沿着单核/巨噬细胞谱系的髓系细胞。第二，确立 每个单独的T型周期蛋白在多大程度上促进了HIV的产生 新感染的单核/巨噬细胞以及单核细胞和巨噬细胞的复制 含有完整潜伏的HIV前病毒基因组的T细胞。这两个目标是 正在进行中。第三，评估一系列腺病毒的有效性 编码多种T-型细胞周期蛋白突变体阻断HIV复制 对两种新感染的正常细胞生理的干扰 含潜伏HIV的单核/巨噬细胞和单核细胞及T细胞 整合的前病毒。第四，明确T型细胞周期蛋白CDK9的作用 鉴定复合体在T细胞活化和髓系分化中的作用 他们下游的目标基因。最终目标是准确地定义 视网膜母细胞瘤相关蛋白PL30的磷酸化位点 差异磷酸化的参与及其生物学意义 在细胞周期进入/退出转换时这种蛋白质的活性。天普大学 医学院、生物化学系和费尔斯研究所 癌症研究完全支持这一应用程序，并为 候选人研究事业的持续发展。 职业发展计划：该计划写得很好，并与 候选人的职业目标；它为研究和提供更多的时间 在艾滋病毒研究中与其他活跃的调查人员合作。IRG是 担心候选人将有多少时间进行研究。基座 关于候选人将继续获得K02奖项的活动，他将 没有达到这个奖项所要求的75%的研究成果。请参阅下面的备注。 研究计划：拟议的研究重点是T-型细胞周期蛋白的作用和 CDK9对T细胞和巨噬细胞中HIV复制的影响及其作用 复合体在T细胞活化和髓系分化中的作用科学的和 该研究具有较高的技术价值。这些实验显然是 已定义，主要由假设驱动，并有可能显著 对文学的贡献。这项研究得到了研究拨款的支持， 一辆R01，一辆R29，以及W.W.史密斯基金会的赠款。请参阅评论 下面。

DESCRIPTION (adapted from the application): This application proposes a plan to enhance the research career of Dr. Xavier Grana. His goals are to achieve excellence in research as well as in teaching at the graduate level. The objective of this application is to obtain salary support for the candidate for a period of five years allowing for an extended period of primary concentration in research and related activities by releasing him from an increased teaching and service load at the Medical School. The short-term research goals are to meet the aims proposed in his currently funded application including an RO1 grant from the NIAID, a grant submitted for renewal to the W.W. Smith Charitable Trust and an R29 from NIGMS. Dr. Grana is a Molecular Biologist and Biochemist. Dr. Grana was a Research Assistant Professor at the Fels Institute for two years. In December of 1996 he was promoted to his current position of tenure-track Assistant Professor in the Department of Biochemistry at Temple University School of Medicine. A career development plan is proposed to enhance the research program of the candidate. The award will allow the candidate to advance in his research abilities and expertise in various related fields in a timely-fashion as well as to extend his research program by increasing the size of his group with graduate students and technical staff. In addition, the candidate plans to enhance his research and academic skills by participating in a number of Symposia and workshops related to the fields in which the candidate seeks to gain additional expertise and by interacting with a number of senior researchers at Temple University School of Medicine. The research plan essentially seeks to meet the specific aims proposed in the candidate's funded RO1 and R29 grants and a renewal grant application submitted to the W.W. Smith Charitable Trust. The combined specific aims are as follows: First, To elucidate the mechanisms leading to upregulation of individual T-type cyclin/CDK9 complexes during both T cell activation and differentiation of myeloid cells along the monocyte/macrophage lineage. Second, to establish to which extent each individual T-type cyclin contributes to HIV productive replication in newly infected monocytes/macrophages and in both monocytes and T cells harboring integrated latent HIV proviral genomes. These two aims are underway. Third, to assess the effectiveness of a series of adenoviruses encoding various T-type cyclin mutants in blocking HIV replication without interfering with normal cellular physiology in both newly infected monocyte/macrophages and monocytes and T cells containing latent HIV integrated proviruses. Fourth, to define the role of T-type cyclintCDK9 complexes in T cell activation and myeloid differentiation by identifying their downstream target genes. The final aim is to define precisely the phosphorylation sites on the retinoblastoma related protein pl30, the kinases involved and the biological significance of the differential phosphorylation of this protein at the cell cycle entry/exit transitions. Temple University School of Medicine, the Department of Biochemistry and the Fels Institute for Cancer Research fully support this application and provide an environment for the continued development of the research career of the candidate. Career Development Plan: The plan is well written and consistent with the candidate's career goals; it affords increased time for research and collaboration with other active investigators in HIV research. The IRG is concerned about the amount of time the candidate will have for research. Based on the activities that the candidate will continue with a K02 award, he will not meet the 75% research effort required by this award. See comments below. Research Plan: The proposed research centers on the role of T-type cyclins and CDK9 on HIV replication in T cells and macrophages, and on the roles of these complexes in T cell activation and myeloid differentiation. The scientific and technical merits of the research are high. The experiments are clearly defined, largely hypothesis driven, and have potential for significant contributions to the literature. The research is supported by research grants, an R01, an R29, and a grant from the W.W. Smith Foundation. See comments below.