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

基本信息

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
项目类别：
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

项目摘要

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。尚不完全了解CHF中这种抑郁功能的基础的分子机制。洛约拉大学芝加哥斯特里奇医学院的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能够雇用新的助理教授（全日制；至少90％致力于研究），以扩大现有的研究环境，包括研究与心力衰竭相关的研究和调节厚细丝蛋白，特别是心脏肌球蛋白结合蛋白C（CMYOBPC）。仅此蛋白质中的突变与一半以上的家族性肥厚性心肌病例有关。此外，最近的数据强烈表明了CMYOBPC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。我们已经确定了一个有力的候选人，他准备过渡到初级任期职位，其个人资料恰好在2009年9月之前加入我们的教职员工。机构承诺已超过该奖项的1 - 2年。由于经济低迷，2009年对这位有前途的助理教授的招聘受到危险。现有的研究环境很强，但通过聘请该候选人会大大增强。关于心力衰竭中心肌功能障碍基本的基本分子机制的准确知识预计将构成开发新的治疗策略来打击这种毁灭性综合征的基础。心力衰竭是死亡率的主要原因，发病率与心脏功能许多方面的不良适应有关，包括收缩蛋白的功能障碍。该提案的目的是使雇用新的助理。教授，研究健康和疾病中的心脏肌球蛋白结合蛋白C。