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生物体的功能都有破坏性的影响。这个 巨噬细胞是单核巨噬细胞的主要成员，是天然巨噬细胞的重要组成部分。 免疫系统。因为巨噬细胞也是艾滋病毒的目标，是生产性病毒感染和 作为一种将感染传播到包括大脑在内的器官的媒介，它对疾病过程的影响是核心的。这个 滥用药物使艾滋病毒感染的复杂性进一步复杂化和加剧。甲基苯丙胺 (冰毒)之所以被选中，是因为它是一种在吸毒人群中越来越受欢迎的药物，并 那些艾滋病毒携带者或有感染艾滋病毒风险的人。这些人的治疗是一个非常复杂的过程，因为它必须 目标是两个性质截然不同的实体。此外，终生治疗艾滋病毒感染的购物车已经 不良毒副作用。作为系统生物学的两个主要途径，全局剖析技术和计算 处理大数据集，成熟后，开始分析来自多变量实验的数据变得可行 (艾滋病毒/冰毒/购物车)。以前的简化论方法排除了在这种复杂程度上进行实验的可能性。 此外，尽管做出了实质性的研究努力，但潜在的分子机制的广泛图景 巨噬细胞在HIV-1感染复杂环境中的功能 被理解。综上所述，我们假设系统生物学方法将提供独特的 将导致识别如何调节人类巨噬细胞的新范式的信息 在艾滋病毒感染的复杂环境中，购物车和冰毒。我们希望我们的实验计划， 通过使用基因组技术检查转录因子和其他核蛋白，计算 生物学和生物信息学分析，将提供独特的信息，将导致识别新的 人类巨噬细胞如何在HIV感染的复杂环境中调节的范例，CART和 冰毒。

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.