Regulation of Angiopoietin mRNA Stability

描述(由申请人提供)：一个为期五年的综合教学和实验室经验的培训计划，以促进涉及分子生物学基础研究的学术生涯的发展。首席研究员已经顺利完成了解剖和临床病理学的实习，目前正在参加为期两年的分子遗传病理学奖学金。为了实现在学术环境中获得终身教职的目标，并将基础研究和学术医学的职业生涯结合起来，我们选择了在涉及血管生成及其在眼病中的作用的分子生物学研究方面获得教育和经验。这一目标将通过一项具有挑战性的研究计划来实现，该计划侧重于与血管生成素-2(Ang2)mRNA稳定性相关的信号转导途径。血管紧张素转换酶2与血管稳定密切相关，也与眼部新生血管有关。初步数据表明，Ang2在转录后受到显著调控，而磷脂酰肌醇-3-激酶(PI3K)活性对Ang2基因的稳定性起着关键作用。我们将确定Ang2 mRNA中的顺式作用元件以及参与PI3K介导的Ang2 mRNA稳定性的相关反式作用因子。Anderson博士(细胞生物学系导师兼主任)和Howard博士(共同导师兼细胞生物学副教授)分别在眼病(包括PI3K在眼部疾病中的作用)和血管生成(包括血管生成素的调节)领域拥有丰富的研究经验。俄克拉荷马大学健康科学中心通过Dean McGee眼科研究所坚定地致力于眼科研究。首席研究员可以使用的设备为这种水平的基于分子的研究提供了必要的现代设备。

DESCRIPTION (provided by applicant): A five year training program of integrated didactic and laboratory experiences to facilitate the development of an academic career involving molecular biology based research. The principle investigator has successfully completed a residency in Anatomic and Clinical Pathology and is currently in a two-year Molecular Genetic Pathology Fellowship. To build toward the goal of obtaining a tenure track position in an academic setting, and to combine a career in both basic research and academic medicine, the choice was made to obtain education and experience in molecular biological research involving angiogenesis and its role in diseases of the eye. This goal will be accomplished through a challenging research proposal focused on signal transduction pathways associated with Angiopoietin-2 (Ang2) mRNA stability. Ang2 is critically involved in blood vessel stability, and is involved in ocular neovascularization. Preliminary data indicate that Ang2 is significantly regulated post-transcriptionally, and that phosphoinositide-3-kinase (PI3K) activity plays a critical role in Ang2 mRNA stability. We will identify cis-acting elements in Ang2 mRNA and the associated trans-acting factors involved in PI3K-mediated Ang2 mRNA stability. Drs. Anderson (Mentor - Chair of the Department of Cell Biology) and Howard (Co-Mentor - Associate Professor of Cell Biology) have extensive research experience in the fields of eye disease (including the role of PI3K in ocular disease) and angiogenesis (including the regulation angiopoietins), respectively. The University of Oklahoma Health Sciences Center is strongly committed to ocular research through the Dean McGee Eye Institute. The facilities available to the principal investigator provide the modem equipment necessary for this level of molecular-based research.