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 trainingnecessary to facilitate the highest quality contemporary biological studies related to frailty, the overall focus ofthe Hopkins OAIC. The resources provided by this core to frailty researchers will include 1) leading interdisciplinaryexpertise for the design and implementation of molecular, genetic and genomic studies related tofrailty; 2) access to state-of-the-art genetic, genomic and molecular technologies; 3) access to a diversity ofhuman 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 toclinically meaningful interventions. By providing these intellectual and physical resources, RC-2 will facilitatethe 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: theestablishment of state-of-the-art infrastructure for genetic data generation and analyses related to frailty; theassemblage of a highly-skilled multidisciplinarv team of experienced investigators; and important scientificprogress related to frailty, including the development of novel endophenotypes, the identification of criticalmolecular pathways associated with frailty, and the development of a frail mouse model. As a result of thisprogress, RC-2 and its leadership has become a national resource for the development of frailty and agingrelatedgenetics research as measured by publications, award-winning national symposia, consortium buildingefforts for combining populations of older adults, development and funding of collaborative genetics studieswith investigators across the country, and provision of training and mentorship for the next generation of investgatorsinterested 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 manyinitial resource challenges, the next stages of basic investigation of frailty require resolution of newly identifiedchallenges in order to test novel hypotheses originating from data generated in the first cycle of funding. Toaddress these challenges, and to test the next generation of hypotheses related to frailty, we propose toexpand the scope of RC-2 beyond human genetics studies into a comprehensive genetics, genomics, andmolecular core that builds on the evolving science, infrastructure, and expertise developed in the first years ofthis center. This evolution will require the leveraging of additional human and infrastructure resources fromacross the Johns Hopkins Medical Institutions towards frailty research, and include facilitating access to seniorleaders with necessary expertise and infrastructure to a) facilitate analytical strategies needed to analyze thevast amounts of genetics and genomics data being generated, b) incorporate measurements of oxidativestress, 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 neededfor additional frailty research. This next stage of goals and advances will enable RC-2 to continue to supportthe most rigorous human genetic studies related to frailty while at the same time enable it to expand its scopeto support studies of molecular pathways identified in genetics studies related to human frailty.
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