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: 7860821
• 负责人: Pieter P. de TOMBE
• 金额: $ 35.61万
• 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 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7860821
• 关键词: Affect; Appointment; Area; Arrhythmia; Atrial Fibrillation; Autonomic nervous system; Award; Binding; Biology; Biophysics; Blood Vessels; Blood flow; C-terminal; Ca(2+)-Transporting ATPase; Cardiac; Cardiac Myocytes; Cardiac Myosins; Cardiomyopathies; Cardiovascular system; Cell membrane; Cell physiology; Cells; Center Core Grants; Characteristics; Chicago; Commit; Congestive Heart Failure; Contractile Proteins; Cytoskeleton; Data; Development; Disease; Economics; Environment; Faculty; Familial Hypertrophic Cardiomyopathy; Functional disorder; Funding; Goals; Health; Heart; Heart failure; Heat Stress Disorders; Heat shock proteins; Hypertrophic Cardiomyopathy; Interview; Ischemia; Knock-out; Knowledge; Letters; Membrane; Microfilaments; Modeling; Molecular; Molecular Biology; Morbidity - disease rate; Mus; Muscular Dystrophies; Mutation; Myocardial; Myocardial Ischemia; Myocardial dysfunction; Myosin ATPase; Patients; Pharmacology; Phosphorylation; Physiology; Poison; Positioning Attribute; Post-Translational Protein Processing; Predisposition; Protein Kinase C; Proteins; Proteolysis; Recruitment Activity; Regulation; Reperfusion Therapy; Research; Research Personnel; Role; Sarcomeres; Sarcoplasmic Reticulum; Secure; Shock; Signal Transduction; Staging; Structure; Structure-Activity Relationship; Syndrome; Testing; Thick Filament; Thin Filament; Thyroid Hormones; Time; Transgenic Organisms; Universities; Ventricular Dysfunction; Visit; base; combat; connectin; depressed; experience; falls; genetic regulatory protein; improved; medical schools; mortality; myosin-binding protein C; novel therapeutics; outcome forecast; polypeptide; professor; programs; receptor function; stress protein; tool; transmission process; treatment strategy

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(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中这种抑制功能的分子机制尚不完全清楚。洛约拉大学芝加哥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。这项建议的目的是获得资金，以便能够聘请一名新的助理教授(全职；至少90%致力于研究)，以扩大现有的研究环境，包括与心力衰竭相关的故障和对粗丝蛋白，特别是心肌肌球蛋白结合蛋白C(CMyoBPC)的调节的研究。仅这种蛋白的突变就与超过一半的有记录的家族性肥厚型心肌病病例有关。此外，最近的数据有力地表明了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的重要作用。我们已经确定了一位强有力的候选人，他准备好过渡到初级终身教职轨道的职位，他的个人资料正好适合在2009年9月加入我们的教职。机构承诺在本奖项的1-2年后得到保证。由于经济不景气，2009年招聘这位有前途的助理教授的工作岌岌可危。现有的研究环境很强，但聘用这位候选人将大大增强这一环境。对心力衰竭中潜在的心肌细胞功能障碍的基本分子机制的准确了解有望成为开发新的治疗策略以对抗这种毁灭性综合征的基础。 心力衰竭是导致死亡的主要原因，发病率与心脏功能的许多方面的不适应有关，包括收缩蛋白的功能障碍。这项建议的目的是有可能聘请一位新的助理教授，研究心肌肌球蛋白结合蛋白C在健康和疾病中的作用。