HIV-1 Integrase Structure and Function as a Therapeutic Target

描述(由候选人提供)：候选人的主要目标是建立一个强有力的、独立的研究计划，以艾滋病毒复制复合体的结构和功能研究为中心。新的发现将被用来发现新的有效的抗逆转录病毒抑制剂。自2003年8月以来，这位候选人一直担任俄亥俄州立大学(OSU)药学院的助理教授。候选人的研究目前得到了以下两项NIH赠款的支持：R01-“HIV-1整合的结构研究”和R21-“作为治疗靶点的HIV-1 Gag结构”。在候选人职业生涯的这个阶段获得独立科学家奖(ISA)将极大地帮助他专注于自己的研究工作。应聘者本学年的教学任务包括指导本科生、专业生和研究生60场讲座和120小时的实验室课程。这些非常重要的教学责任减慢了考生的研究活动。如果获得ISA，该大学将把考生的教学负担降低到-15%的努力水平。考生的研究项目将从课程负担的减少中受益匪浅。他将有时间亲自从事实验室工作，并直接监督他的博士后研究员和研究生。候选人将参加科学会议和研讨会，以增进他在未来计划从事的领域的知识，并与该领域的其他科学家更密切地互动。俄亥俄州立大学的设施和研究环境也有利于实现所述目标。候选人目前的研究活动旨在阐明HIV-1 IN如何与同源核酸和细胞辅助因子相互作用，并识别抑制这些功能基本相互作用的新小分子。HIV-1 IN通常被视为一个重要的治疗靶点，原因如下：IN的催化活性是病毒复制所必需的，没有与IN密切相关的细胞等价物，以及特定的IN抑制剂很可能有效地对抗目前针对逆转录酶、蛋白酶和融合的现有治疗方法的耐药性。有关HIV-1IN核蛋白复合体功能的详细结构和机制信息可能有助于药物设计工作。候选人的研究小组正在利用创新的生化/生物物理方法解决这些重要问题，包括候选人实验室开发的质谱学蛋白质足迹技术。

DESCRIPTION (provided by candidate): The candidate's main objective is to establish a vigorous, independent research program centered on structure and function studies of HIV replication complexes. The new findings will be exploited to discover novel effective antiretroviral inhibitors. Since August of 2003 the candidate has been Assistant Professor at the Ohio State University (OSU) College of Pharmacy. The candidate's research is currently supported by the following two NIH grants: R01 - "structural studies of HIV-1 integration" and R21 - "HIV-1 Gag structure as a therapeutic target". An Independent Scientist Award (ISA) at this stage of the candidate's career would help him enormously to focus on his research endeavors. The candidate's teaching load for the current academic year includes instructing undergraduate, professional and graduate students 60 lectures and 120 hrs laboratory courses. These very significant teaching responsibilities slow down the candidate's research activities. If awarded an ISA, the University will reduce the candidate's teaching load to an -15% effort level. The candidate's research program would benefit greatly from this reduced course load. He would have time to pursue the lab work himself and directly supervise his postdoctoral fellow and graduate students. The candidate would attend scientific meetings and workshops to enhance his knowledge in the areas that he plans to pursue in future and more closely interact with other scientists in the field. The facilities and research environment at OSU are also conducive to the stated goals. The candidate's current research activities aim to elucidate how HIV-1 IN interacts with cognate nucleic acids and cellular cofactors, and identify new small molecules inhibiting these functionally essential interactions. HIV-1 IN is commonly viewed as an important therapeutic target for the following reasons: catalytic activities of IN are required for viral replication, there is no closely related cellular equivalent of IN, and specific IN inhibitors are likely to be effective against viral strains resistant to currently available therapies targeting reverse transcriptase, protease, and fusion. Detailed structural and mechanistic information on functional HIV-1 IN nucleoprotein complexes could aid drug design efforts. The candidate's research group is addressing these important problems using innovative biochemical/biophysical approaches including mass spectrometric protein footprinting technologies developed in the candidate's laboratory.