Smooth Muscle Plasticity: A COBRE

描述(由申请人提供)：本提案旨在为内华达大学里诺分校(UNR)卓越生物医学研究中心(COBRE)续期资金。科布雷扩大了研究基础设施，并帮助发展了几位非常有前途的年轻调查人员的职业生涯。该中心在平滑肌肉生物学方面有很强的主题重点。Cobre由5个项目组成，这些项目正在研究平滑肌可塑性的各个方面。项目1：糖尿病胃轻瘫中结构缺陷和运动缺陷之间的相关性将由Grant Hennig博士领导；项目2：Phopholamban和CaM Kinase II在平滑肌可塑性中的作用将由Brian Perrino博士领导；项目3：用于确定平滑肌力学调控机制的体外模型系统将由Josh Baker博士领导；项目4：由microRNAs调控的平滑肌肥大及其靶基因将由Seungil Ro博士领导；项目5：过度活跃的膀胱中对拉伸依赖的钾通道的调控将由Sang Don Koh博士领导。这些项目得到核心实验室设施的支持：核心A：行政和教职发展；核心B：分子表达和转基因；核心C：蛋白质表达和细胞形态；以及核心D：动态成像。Cobre将由以下人员管理：i)中央Cobre管理机构，由PI和Co-Pi组成，由行政助理和计算机专家组成；ii)内部咨询委员会(Lac)，为每个项目负责人提供指导；iii)外部咨询委员会(EAC)，由平滑肌肉生物学领域的领导人组成。Lac的导师是杰出的科学家，在生物医学研究方面拥有多产的职业生涯。LAC为职业发展建立里程碑，对实现里程碑的进展进行形成性和总结性评估，并协助项目领导人实现发展独立资助和可持续研究职业的中心目标。科布雷由肯顿·桑德斯博士和克里斯汀·克雷莫博士分别担任圆周率和共同圆周率。PI和Co-PI是非常合格的，在科布雷的主题重点方面拥有多年的行政和科学经验。 公共卫生相关性(由申请人提供)：平滑肌肉在肌肉谱系中是独一无二的，因为它们会对各种刺激做出反应而改变表型。病理生理状态是由平滑肌组织的表型变化引起的，但重塑和肥大的原因和后果尚不清楚。将使用几种平滑肌肉的疾病模型来了解表型变化如何对病理生理学做出贡献。

DESCRIPTION (provided by applicant): This proposal is to renew funding for the Smooth Muscle Plasticity Center of Biomedical Research Excellence (COBRE) at the University of Nevada, Reno (UNR). The COBRE has expanded the research infrastructure and helped to develop the careers of several highly promising young investigators. The center has a strong thematic focus in smooth muscle biology. The COBRE consists of 5 projects that are investigating various aspects of smooth muscle plasticity. Project 1: Correlation between structural and motor defects in diabetic gastroparesis to be headed by Dr. Grant Hennig; Project 2: Phopholamban and CaM Kinase II in smooth muscle plasticity to be headed by Dr. Brian Perrino; Project 3: An in vitro model system for determining regulatory mechanisms for smooth muscle mechanics to be led by Dr. Josh Baker; Project 4: Smooth muscle hypertrophy regulated by microRNAs and their target genes to be headed by Dr. Seungil Ro; Project 5: Stretch-dependent potassium channel regulation in overactive bladder to be led by Dr. Sang Don Koh. The projects are supported by Core lab facilities: Core A: Administration and faculty development; Core B: Molecular expression and transgenics; Core C: Protein expression and cell morphology; and Core D: Dynamic imaging. The COBRE will be administered by: i) the Central COBRE Administration consisting of the PI and Co-PI, administrative assistant and computer specialist; ii) an Internal Advisory Committee (lAC) with mentors for each project leader; and iii) an External Advisory Committee (EAC) consisting of leaders in smooth muscle biology. Mentors in the lAC are distinguished scientists with productive careers in biomedical research. The lAC establishes milestones for career development, performs formative and summative evaluation of progress toward milestones, and assists the Project Leaders in the central goal of developing independent funding and sustainable research careers. The COBRE is led by Drs. Kenton Sanders and Christine Cremo as PI and Co-PI, respectively. The PI and Co-PI are highly qualified, with many years of administrative and scientific experience in the thematic focus of the COBRE. PUBLIC HEALTH RELEVANCE (provided by applicant): Smooth muscles are unique among muscle lineages because they change phenotype in response to a variety of stimuli. Pathophysiological conditions result from phenotypic changes in smooth muscle tissues, but the cause and consequences of remodeling and hypertrophy are not well understood. Several disease models of smooth muscles will be used to learn how phenotypic change contributes to pathophysiology.