GENETICS, GENOMICS, AND MOLECULAR CORE

6.5.拟议的遗传学、基因组学和分子资源核心（RC-2）活动概述： 6.5.a）具体目标：RC-2的目的是提供人力资源、基础设施和培训 为了促进与脆弱相关的最高质量的当代生物学研究， 霍普金斯的OAIC这个核心为脆弱研究人员提供的资源将包括1）领先的跨学科 设计和实施分子、遗传和基因组研究的专业知识， 脆弱性; 2）获得最先进的遗传、基因组和分子技术; 3）获得多种 人类和虚弱动物模型DNA、组织和血清样本; 4）遗传学方面的指导和培训， 基因组学和分子生物学; 5）专业知识，以帮助翻译分子，遗传和基因组研究结果， 有临床意义的干预措施。通过提供这些知识和物质资源，RC-2将促进 阐明虚弱和相关生物脆弱性的临床相关生物学途径， 从而确定有希望的目标，以开发预防或减轻虚弱的干预措施。 RC-2供资的头几年通过以下方式在实现这些目标方面取得了重大进展： 建立最先进的基础设施，用于生成和分析与脆弱性有关的遗传数据; 由经验丰富的研究人员组成的高技能多学科团队的集合;以及重要的科学 与虚弱相关的进展，包括新的内在表型的开发，关键的 与虚弱相关的分子途径，以及虚弱小鼠模型的开发。由于这种 进步，RC-2及其领导已成为国家资源的发展脆弱性和老龄化有关 通过出版物、获奖的国家研讨会、联盟建设来衡量遗传学研究 努力结合老年人群体，发展和资助合作遗传学研究 与全国各地的调查人员合作，并为下一代投资者提供培训和指导 对研究虚弱的分子和遗传基础及其转化为临床护理感兴趣。 尽管RC-2申办的研究者已经取得了实质性的科学进展，并解决了许多 由于最初的资源挑战，对脆弱性进行基本调查的下一阶段需要解决新发现的 为了检验根据第一个供资周期产生的数据提出的新假设，对一些挑战进行了评估。到 为了应对这些挑战，并测试与脆弱相关的下一代假设，我们建议 将RC-2的范围从人类遗传学研究扩展到全面的遗传学，基因组学， 分子核心，建立在不断发展的科学，基础设施和专业知识，在第一年的发展 这个中心。这一演变将需要利用更多的人力和基础设施资源， 在约翰霍普金斯医疗机构对脆弱的研究，并包括促进访问高级 具有必要的专业知识和基础设施的领导者，a）促进分析所需的分析战略， 产生了大量的遗传学和基因组学数据，B）结合了氧化还原的测量， 压力线粒体！功能，DNA甲基化和基因表达到RC-2赞助的脆弱性研究， 和c）开发用于所需的人类和/或动物生物样品和表型数据的改进的获取途径 进行更多的脆弱性研究下一阶段的目标和进展将使RC-2能够继续支持 最严格的人类基因研究与脆弱有关，同时使其能够扩大其范围 支持在与人类脆弱性相关的遗传学研究中确定的分子途径的研究。

6.5. Overview of Proposed Genetics, Genomics and Molecular Resource Core (RC-2) Activities: 6.5.a) Specific Aims: The purpose of RC-2 is to provide the human resources, infrastructure, and training necessary to facilitate the highest quality contemporary biological studies related to frailty, the overall focus of the Hopkins OAIC. The resources provided by this core to frailty researchers will include 1) leading interdisciplinary expertise for the design and implementation of molecular, genetic and genomic studies related to frailty; 2) access to state-of-the-art genetic, genomic and molecular technologies; 3) access to a diversity of human and frail animal model DNA, tissue and serum samples; 4) mentorship and training in genetics, genomics, and molecular biology; and 5) expertise to help translate molecular, genetic and genomic findings to clinically meaningful interventions. By providing these intellectual and physical resources, RC-2 will facilitate the elucidation of clinically relevant biological pathways that underlie frailty and related biological vulnerability, and thereby identify promising targets toward which to develop interventions that prevent or attenuate frailty. The first years of RC-2 funding have produced significant progress towards these goals through: the establishment of state-of-the-art infrastructure for genetic data generation and analyses related to frailty; the assemblage of a highly-skilled multidisciplinarv team of experienced investigators; and important scientific progress related to frailty, including the development of novel endophenotypes, the identification of critical molecular pathways associated with frailty, and the development of a frail mouse model. As a result of this progress, RC-2 and its leadership has become a national resource for the development of frailty and agingrelated genetics research as measured by publications, award-winning national symposia, consortium building efforts for combining populations of older adults, development and funding of collaborative genetics studies with investigators across the country, and provision of training and mentorship for the next generation of investgators interested in studying the molecular and genetic basis of frailty and its translation into clinical care. Although RC-2 sponsored investigators have made substantial scientific progress and have resolved many initial resource challenges, the next stages of basic investigation of frailty require resolution of newly identified challenges in order to test novel hypotheses originating from data generated in the first cycle of funding. To address these challenges, and to test the next generation of hypotheses related to frailty, we propose to expand the scope of RC-2 beyond human genetics studies into a comprehensive genetics, genomics, and molecular core that builds on the evolving science, infrastructure, and expertise developed in the first years of this center. This evolution will require the leveraging of additional human and infrastructure resources from across the Johns Hopkins Medical Institutions towards frailty research, and include facilitating access to senior leaders with necessary expertise and infrastructure to a) facilitate analytical strategies needed to analyze the vast amounts of genetics and genomics data being generated, b) incorporate measurements of oxidative stress, mitochondria! function, DNA methylation, and gene expression into RC-2 sponsored frailty research, and c) develop improved access to human and/or animal biological samples and phenotypic data for needed for additional frailty research. This next stage of goals and advances will enable RC-2 to continue to support the most rigorous human genetic studies related to frailty while at the same time enable it to expand its scope to support studies of molecular pathways identified in genetics studies related to human frailty.