Case Proteomics Center for HIV/AIDS and Drug Abuse

描述(由申请人提供)：这份P20申请书建议建立艾滋病毒/艾滋病和药物滥用案例蛋白质组学中心，该中心旨在应用最先进的蛋白质组学和系统生物学工具在药物滥用的背景下研究艾滋病毒的发病机制，并提供艾滋病毒感染、与其他病毒合并感染和药物滥用的重要生物标志物。在试验阶段，我们会进行三项互相关联的计划，以便更深入了解同时接触令人上瘾的药物对爱滋病病毒感染者的免疫功能和活动的影响，以及丙型肝炎病毒的重要辅助因素。在这些项目中，每个项目都将直接检查上皮细胞或T细胞的蛋白质组反应，并平行检查受影响患者的血浆读数。这些项目的一个主要成果将是开发可用于大规模人口研究的信息生物标记物和方法，以进一步评估药物使用对艾滋病毒疾病的影响。该中心将由蛋白质组学案例中心主任、国际公认的蛋白质组学和系统生物学专家Mark Chance博士与分子生物学和微生物学系主任、艾滋病研究案例中心(CFAR)联席主任、艾滋病毒/艾滋病分子生物学专家乔纳森·卡恩博士合作领导。试点项目是凯斯大学现有的一个强大的多学科小组的工作，该小组结合了医学系、分子生物学和微生物学系、生物科学系(牙科学院)和CFAR在艾滋病毒/艾滋病方面的重要生物学专业知识。这些研究人员已经收集了重要的分子生物学和蛋白质组学数据，在蛋白质组学和生物信息学核心提供服务的三个试点项目的背景下提供了可验证的假说。这三个项目将在CFAR病例临床核心的配合下，招募合适的患者队列提供相关样本。核心的蛋白质组学团队随后将对病例和相关对照人群进行蛋白质组表达分析，并向生物信息学团队提供具有统计意义的目标。该团队不仅将在将要解决的生物学问题的背景下提供网络分析和途径识别，而且将把蛋白质组学途径模型与已知的药物成瘾和艾滋病毒致病途径联系起来，并将通过蛋白质组学和微阵列数据的组合分析来推断新的子网络。

DESCRIPTION (provided by applicant): This P20 application proposes the creation of the Case Proteomics Center in HIV/AIDS & Drug Abuse, which is designed to apply state-of-the art proteomics and systems biology tools to investigate HIV pathogenesis in the context of drug abuse and provide significant biomarkers of HIV infection, co-infection with other viruses, and drug abuse. During the pilot phase, we will undertake three inter-related projects designed to provide a better understanding of the impact on immune function and activity in HIV-infected individuals who are also exposed to addictive drugs, and the important viral co-factor Hepatitis C (HCV). In each of these projects there will be a direct examination of the proteomic responses in epithelial or T-cells and parallel examination of plasma readouts from affected patients. A major outcome of these projects will be development of informative biomarkers and methods that can be used in large-scale population studies to further evaluate the impact of drug use on HIV disease. The Center will be directed by Dr Mark Chance, Director of the Case Center for Proteomics, and an internationally recognized expert in proteomics and system biology in collaboration with Dr Jonathan Karn, Chair of the Department of Molecular Biology & Microbiology and Co-Director of the Case Center for AIDS Research (CFAR), and an expert in HIV/AIDS molecular biology. The pilot projects are the work of a strong pre-existing multi-disciplinary team at Case that combines significant biological expertise in HIV/AIDS within the Department of Medicine, the Department of Molecular Biology & Microbiology, the Department of Biological Sciences (Dental School) and CFAR. These investigators have already assembled significant molecular biology and proteomics data to provide testable hypotheses within the context of three Pilot Projects served by a Proteomics and Bioinformatics Core. The three projects, with the cooperation of the clinical core of the Case CFAR, will recruit appropriate patient cohorts to provide relevant samples. The proteomics team in the Core will then conduct proteome expression analysis of cases versus relevant control populations, with statistically significant targets provided to the Bioinformatics team. This team will not only provide network analysis and pathway identification within the context of the biological questions to be addressed, but will correlate the proteomics pathway models with known pathways of drug addiction and HIV pathogenesis and will infer novel sub-networks by combined analysis of proteomics and microarray data.