Transcriptional Regulation, the Nuclear Proteome, and HIV/Meth/cART: From Profili

转录调控、核蛋白质组和 HIV/Meth/cART：来自 Profili

基本信息

批准号：
8287636
负责人：
PAWEL S CIBOROWSKI
金额：
$ 62.31万
依托单位：
UNIVERSITY OF NEBRASKA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-17 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8287636
关键词：
Affect Anti-Retroviral Agents Bioinformatics Biological Brain Cardiovascular system Cells Chronic Disease Clinical Complex Computational Biology Computational Technique Data Data Analyses Data Set Disease Drug abuse Drug usage Environment Etiology Experimental Models Feedback Figs - dietary Genetic Transcription Goals HIV HIV Infections HIV-1 Human Immune system Individual Infection Information Systems Laboratories Lead Life Mass Spectrum Analysis Measures Methamphetamine Modeling Molecular Mononuclear Natural Immunity Nature Nuclear Nuclear Proteins Organ Organism Patients Phagocytes Pharmaceutical Preparations Phenotype Physiological Play Population Process Proteome Proteomics Regulation Research Research Personnel Risk Role Signal Pathway System Systems Analysis Systems Biology Techniques Testing Therapeutic Intervention Toxic effect Transcriptional Regulation Validation Virus Diseases antiretroviral therapy base drug of abuse expectation innovation macrophage member monocyte novel research clinical testing research study success transcription factor transcriptomics

项目摘要

ABSTRACT: HIV-1 infection and drug of abuse have devastating effects on function of the entire organism. The macrophage is the prime member of the mononuclear phagocyte class of cells and a key part of innate immunity system. Because the macrophage is also a target of HIV, a reservoir of productive viral infection and a vehicle to spread infection to organs including the brain, its impact on the course of disease is central. The complexity of HIV infection is further complicated and intensified by use of drugs of abuse. Methamphetamine (METH) was chosen since it is a drug with increasing popularity among the drug-abusing population and used by those with, or at risk for, HIV. Treatment of these individuals is a very complex process because it has to target two entities that are quite different in nature. In addition, life-long cART treatment of HIV infection has adverse toxic effects. As two main avenues of Systems Biology, global profiling techniques and computational processing of large data sets, mature, it becomes feasible to start analyzing data from multivariate experiments (HIV/METH/cART). Prior reductionist approaches precluded performing experiments at this level of complexity. Moreover, despite substantive research efforts, the broad picture of molecular mechanisms underlying functions of macrophages in the complex environment of HIV-1 infection METH use and/or cART is far from being understood. Summarizing, we hypothesize that the systems biology approach will provide unique information which will lead to identification of new paradigm how the human macrophage is regulated in the complex environment of HIV infection, cART and METH. We expect that our experimemtal plan, examining transcription factors and other nuclear proteins through the use of omic techniques, computational biology and bioinformatic analyses, will provide unique information which will lead to identification of new paradigms in how the human macrophage is regulated in the complex environment of HIV infection, cART and METH.

抽象的： HIV-1感染和滥用药物对整个生物的功能具有毁灭性的影响。这巨噬细胞是单核吞噬细胞类的主要成员，也是先天的关键部分免疫系统。因为巨噬细胞也是艾滋病毒的靶标，是生产性病毒感染和将感染传播到包括大脑在内的器官的车辆，其对疾病进程的影响是核心。这艾滋病毒感染的复杂性更加复杂，并通过使用滥用药物而加剧。甲基苯丙胺选择（甲基苯丙胺）是因为它是一种药物，在滥用毒品的人群中越来越受欢迎并使用由有艾滋病毒或有风险的人。这些人的治疗是一个非常复杂的过程，因为它必须针对两个本质上完全不同的实体。此外，终生的艾滋病毒感染治疗不良毒性作用。作为系统生物学的两个主要途径，全球分析技术和计算处理大型数据集，成熟，开始分析来自多元实验的数据变得可行（艾滋病毒/甲基苯/货车）。先前的还原主义方法无法在这种复杂性水平上进行执行实验。此外，尽管进行了实质性的研究工作，但分子机制的广泛了解 HIV-1感染的复杂环境中巨噬细胞的功能甲基甲基苯丙胺的使用和/或推车远离被理解。总而言之，我们假设系统生物学方法将提供独特将导致新范式识别人类巨噬细胞的信息的信息在艾滋病毒感染，推车和甲基苯丙胺的复杂环境中。我们希望我们的实验计划，通过使用OMIC技术检查转录因子和其他核蛋白质生物学和生物信息学分析将提供独特的信息，这将导致识别新的信息在HIV感染，购物车和CART和冰毒。