Physiologic Genomics of Pulmonary Hypertension & RVH

肺动脉高压的生理基因组学

• 批准号: 6915716
• 负责人: Sina A Gharib
• 金额: $ 12.91万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-10 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6915716
• 关键词: bioinformatics; computer data analysis; disease /disorder model; functional /structural genomics; gene expression; gene expression profiling; gene induction /repression; immunocytochemistry; in situ hybridization; laboratory mouse; laser capture microdissection; mathematical model; method development; microarray technology; molecular pathology; northern blottings; polymerase chain reaction; pulmonary hypertension; remission /regression; statistics /biometry; ventricular hypertrophy; western blottings

DESCRIPTION (provided by applicant): Recent breakthroughs in molecular biotechnology are allowing simultaneous measurements of thousands of gene products in a single experiment. Understanding the complexity of such datasets requires a thorough training in both traditional molecular biology and computational sciences. The primary goal of this mentored development award is to provide the Principal Investigator (PI) the training and environmental support necessary to develop into an independent computational molecular biologist in the field of cardiopulmonary biology. This multidisciplinary award will support the PI's training in the disciplines of physiology, molecular biology, computational biology and statistics, and allow him to combine these tools to investigate the molecular basis of pulmonary hypertension and right ventricular remodeling. The primary scientific goal of this project is to discover several key genetic pathways in the pathogenesis of pulmonary hypertension and right ventricular hypertrophy (RVH) by applying rigorous statistical methods to data generated from global gene expression profiling. Two concurrent but interdependent Specific Aims will be pursued. Aim 1 will identify, characterize and confirm a set of temporally and functionally related genes that are crucial in the development and regression of pulmonary hypertension and RVH in mice. Different mouse models of pulmonary hypertension and RVH will be compared to search for common genetic pathways during both the progression and regression of these processes. Additionally, the hypothesis that pulmonary vascular and right ventricular remodeling share several common molecular pathways will be tested. This approach will uniquely provide global insights into the complex molecular processes activated during vascular and ventricular remodeling. Aim 2 will allow the PI to develop and improve computational methods to normalize raw data, determine statistically significant gene expression, and apply clustering strategies to microarray-generated datasets. The results of investigations undertaken in Aim 2 will be applied directly to data generated in Aim 1. Pursuit of a Master's of Science in Computational Biology will further enhance the PI's ability to successfully merge complex mathematical models with datasets resulting from large-scale gene expression profiling. Ultimately, this mentored research career award will allow the PI to develop into an independent computational molecular biologist and pursue an academic research career in the physiologic genomics of the cardiopulmonary system.

描述(由申请人提供)： 最近分子生物技术的突破使人们可以在一次实验中同时测量数千种基因产物。理解这类数据集的复杂性需要在传统分子生物学和计算科学方面进行全面的培训。该指导发展奖的主要目标是为首席调查员(PI)提供必要的培训和环境支持，以发展成为心肺生物学领域的独立计算分子生物学家。这一多学科奖项将支持PI在生理学、分子生物学、计算生物学和统计学领域的培训，并使他能够结合这些工具来研究肺动脉高压和右室重构的分子基础。该项目的主要科学目标是通过对全球基因表达谱产生的数据应用严格的统计方法来发现肺动脉高压和右室肥厚(RVH)发病机制中的几个关键遗传途径。将追求两个同时但相互依存的具体目标。目的1将鉴定、鉴定和确认一组时间和功能相关的基因，这些基因在小鼠的肺动脉高压和RVH的发展和消退中起关键作用。将比较不同的肺动脉高压和RVH小鼠模型，以寻找在这些过程的进展和消退过程中的共同遗传途径。此外，肺血管和右室重构共享几个共同的分子通路的假设将得到验证。这种方法将独一无二地提供对血管和心室重塑过程中激活的复杂分子过程的全球洞察。AIM 2将允许PI开发和改进计算方法，以使原始数据标准化，确定具有统计意义的基因表达，并将聚类策略应用于微阵列生成的数据集。在AIM 2中进行的研究结果将直接应用于AIM 1中产生的数据。攻读计算生物学理学硕士学位将进一步提高PI成功地将复杂的数学模型与大规模基因表达图谱产生的数据集合并的能力。最终，这个有指导的研究生涯奖将使PI发展成为一名独立的计算分子生物学家，并在心肺系统的生理基因组学方面追求学术研究生涯。