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

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中这种功能被抑制的分子机制尚不完全清楚。洛约拉大学芝加哥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。本提案的目的是获得资金，以便聘请新的助理教授（全职；至少90%的精力用于研究），以扩大现有的研究环境，包括研究心力衰竭相关的功能障碍和厚丝蛋白的调节，特别是心肌肌球蛋白结合蛋白C （cMyoBPC）。该蛋白的突变与半数以上的家族性肥厚性心肌病有关。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起重要作用。我们已经确定了一位很有实力的候选人，他已经准备好过渡到初级终身职位，并且在2009年9月之前加入我们的教职员工。机构承诺保证超过该奖项的1-2年。由于经济不景气，这位前途无量的助理教授在2009年的招聘前景堪忧。现有的研究环境是强大的，但将大大提高聘用该候选人。对心力衰竭中心肌细胞功能障碍的基本分子机制的准确认识，有望为开发新的治疗策略奠定基础，以对抗这种毁灭性的综合征。

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.