Myosin Binding Protein C structure-function relationships in the failing heart

衰竭心脏中肌球蛋白结合蛋白 C 的结构与功能关系

• 批准号: 7937867
• 负责人: Pieter P. de TOMBE
• 金额: $ 34.66万
• 依托单位: LOYOLA UNIVERSITY CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7937867
• 关键词: Myosin; Binding; Protein; structure; function

DESCRIPTION (provided by applicant): Congestive heart failure (CHF) is associated with an abnormality in cardiac cell function. The molecular mechanisms that underlie this depressed function in CHF are not completely understood. The Major research theme at the Department of Cell and Molecular Physiology at the Loyola University Chicago Stritch School of Medicine is Cardiovascular Research with a special focus on heart failure. The purpose of this proposal is to secure funds to enable hiring of a new Assistant Professor (full time; at least 90% effort dedicated to research) to expand the existing research environment to include studies into heart failure associated malfunction and regulation of thick filament proteins, in particular cardiac Myosin Binding Protein C (cMyoBPC). Mutations in this protein alone are associated with over half of the documented cases of familial hypertrophic cardiomyopathy. In addition, recent data strongly suggest an important role for post-translational modification (phosphorylation) of cMyoBPC in heart failure and ischemia/reperfusion myocardial dysfunction. We have identified a strong candidate who is ready to transition to a junior tenure-track position with a profile that is just right to join our faculty by September 2009. Institutional commitment is secured beyond years 1-2 of this award. Due to the economic downturn, hiring of this promising Assistant Professor in 2009 is in jeopardy. The existing research environment is strong, but would be greatly enhanced by hiring of this candidate. Accurate knowledge regarding the fundamental molecular mechanisms underlying cardiac myocyte dysfunction in heart failure is expected to form the basis for the development of new therapeutic strategies to combat this devastating syndrome. Heart failure is a leading cause of mortality and morbidity is associated with maladaptation of many aspects of cardiac function, including dysfunction of contractile proteins. The purpose of this proposal is to make possible hiring of a new Asst. Prof, to study cardiac Myosin Binding Protein C in health and disease.

描述（由申请人提供）：充血性心力衰竭（CHF）与心脏细胞功能异常有关。CHF中这种功能抑制的分子机制尚未完全清楚。芝加哥洛约拉大学斯特里奇医学院细胞和分子生理学系的主要研究主题是心血管研究，特别关注心力衰竭。该提案的目的是确保资金，以便聘请一名新的助理教授（全职;至少90%的努力致力于研究），以扩大现有的研究环境，包括心力衰竭相关的功能障碍和粗丝蛋白的调节，特别是心肌肌球蛋白结合蛋白C（cMyoBPC）。这种蛋白质的突变与超过一半的家族性肥厚型心肌病病例有关。此外，最近的数据强烈表明，cMyoBPC的翻译后修饰（磷酸化）在心力衰竭和缺血/再灌注心肌功能障碍中发挥重要作用。我们已经确定了一个强有力的候选人谁是准备过渡到一个初级终身职位的轨道位置与配置文件是刚刚好加入我们的教师在2009年9月。该奖项的第1-2年之后，机构承诺得到保证。由于经济衰退，这位有前途的助理教授在2009年的招聘处于危险之中。现有的研究环境是强大的，但将大大加强雇用这位候选人。关于心力衰竭中心肌细胞功能障碍的基本分子机制的准确知识有望成为开发新的治疗策略以对抗这种破坏性综合征的基础。 心力衰竭是死亡的主要原因，发病与心脏功能的许多方面的适应不良有关，包括收缩蛋白的功能障碍。该提案的目的是为了聘请一位新的助理教授，研究心脏肌球蛋白结合蛋白C在健康和疾病中的作用。