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

摘要： HIV-1感染和滥用药物对整个机体的功能具有破坏性影响。的 巨噬细胞是单核吞噬细胞类细胞的主要成员，是先天性巨噬细胞的关键部分。 免疫系统因为巨噬细胞也是HIV的目标，是生产性病毒感染的储存库， 作为将感染传播到包括大脑在内的器官的媒介，它对疾病进程的影响至关重要。的 艾滋病毒感染的复杂性因滥用药物而进一步复杂化和加剧。甲基苯丙胺 选择甲氧西林（METH）是因为它是一种在药物滥用人群中越来越受欢迎的药物， 感染艾滋病毒或有感染艾滋病毒风险的人。治疗这些人是一个非常复杂的过程，因为它必须 针对两个性质完全不同的实体此外，艾滋病毒感染的终身cART治疗 不良毒性作用。作为系统生物学的两个主要研究方向，全局轮廓技术和计算轮廓技术是系统生物学研究的两个重要领域。 处理大型数据集，成熟，从多变量实验开始分析数据变得可行 (HIV/METH/cART）。先前的还原论方法排除了在这种复杂程度上进行实验。 此外，尽管有大量的研究工作，但潜在的分子机制的广泛情况， 巨噬细胞在HIV-1感染的复杂环境中的功能 被理解总之，我们假设系统生物学方法将提供独特的 这将导致识别人类巨噬细胞如何调节的新范例的信息 在艾滋病毒感染、cART和METH的复杂环境中。我们希望我们的实验计划， 研究转录因子和其他核蛋白通过使用组学技术，计算 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 人类巨噬细胞在HIV感染、cART和 METH.

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.