MOLECULAR PHYSIOLOGY OF THE HEART AND ITS VASCULATURE

麻省理工学院“心脏及其血管的分子生理学”项目将研究心脏和相关组织的分子生物学，以及导致心血管疾病的异常。它的主要目标是确定生化、细胞生物学和遗传决定因素，这些决定因素是正常心脏血管发育和心血管功能的基础，当改变时，容易或导致个人患心血管疾病。这项工作将主要集中在小鼠的生理学和病理学模型以及分子生物学和遗传学的使用上，并扩大我们对心血管系统功能和故障的知识。这项工作有望为阐明未来心血管疾病诊断、治疗和预防中基于遗传学的、有针对性的进展所需的基本分子生理学机制做出重大贡献。该计划将联系在一起，并将促进麻省理工学院生物系高级教员之间的广泛互动。这些研究人员使用各种分子生物学方法来研究心血管系统的结构和功能。他们一直在利用体细胞基因技术揭示未知的生化途径和未知的基因表达生化途径；通过转基因/嵌合/敲除小鼠模型阐明特定基因在整个生物体水平上的生物效应并开发新的疾病模型系统；以及利用新的基因作图技术描绘人类疾病的分子基础。各种项目的性质涉及计划参与者之间的广泛合作，他们将为解决常见问题贡献各种分子、细胞、遗传学、基因组学和生理学方法。整个计划将通过转基因小鼠、细胞培养和管理的共享设施来加强。该计划项目提案是由NHLBI赞助的麻省理工学院分子生物学卓越计划(POEMB)的一个非常成功的12年计划的产物。根据POEMB的经验，我们预计拟议的互动网络将促进各个实验室的研究成果，并大大有助于我们对心血管生理学和病理生理学的理解。

The MIT Program of 'Molecular Physiology of the Heart and its Vasculature' will investigate the molecular biology of the heart and appropriately related tissues, and the abnormalities that lead to cardiovascular disorders. It's main goals are to identify biochemical, cell biologic, and genetic determinants that underlie normal cardiac vascular development and cardiovascular function and that, when altered, predispose or cause individuals to develop cardiovascular diseases. The work will focus primarily on murine models of physiology and pathology and the use of molecular biology and genetics and expand our knowledge of the function and malfunction of the cardiovascular system. This work is expected to contribute significantly to the elucidation of the basic molecular physiologic mechanisms required for future genetics-based, targeted advances in the diagnosis, treatment and prevention of cardiovascular disease. The Program links together and will foster extensive interactions among senior faculty members of the MIT Department of Biology. These investigators employ a variety of molecular biologic approaches to study the structure and function of the cardiovascular system. They have been uncovering unsuspected biochemical pathway unsuspected biochemical pathways of gene expression with somatic genetic techniques; elucidating the biologic effects of specific genes at the whole organism level and developing novel disease model systems by employing transgenic/chimeric/knockout mouse models; and delineating the molecular basis of human diseases with novel gene mapping techniques. The nature of the various projects involves extensive collaboration among Program participants, who will contribute a wide variety of molecular, cellular, genetic, genomics and physiologic approaches to the resolution of common problems. The overall Program will be strengthened by shared facilities for transgenic mice, cell culture, and administration. This Program Project proposal is an outgrowth of the highly successful 12 year MIT Program of Excellence in Molecular Biology (POEMB) sponsored by the NHLBI. Based on the POEMB experience, we expect that the proposed network of interactions will accelerate research accomplishments in the individual laboratories and significantly contribute to our understanding of cardiovascular physiology and pathophysiology.