TRAINING IN MOLECULAR VIROLOGY AND AIDS PATHOGENESIS

分子病毒学和艾滋病发病机制培训

• 批准号: 2390111
• 负责人: Anne D Lewis
• 金额: $ 8.4万
• 依托单位: CHILDREN'S HOSPITAL (COLUMBUS)
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-04-01 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2390111
• 关键词: AIDS; AIDS education /prevention; Macaca nemestrina; disease /disorder model; human immunodeficiency virus 1; model design /development; molecular biology; recombinant virus; science education; simian immunodeficiency virus; tissue /cell culture; training

A training program for Dr. Anne Lewis is described in this Physician Scientist Award (K11) application. The program is designed to provide Dr. Lewis with the skills to investigate viral pathogenesis at a molecular level in order for her to ultimately become an independent investigator. Dr. Lewis is a board certified veterinary pathologist who has recently returned to graduate school to pursue a Ph.D. degree in Experimental Pathology in the Department of Veterinary Pathobiology at the Ohio State University. She is co-sponsored by Dr. Philip Johnson and Dr. Paul Stromberg. The specific aims of Phase I of the training program for Dr. Lewis are: (i) to obtain basic training in virology, tissue culture and molecular biology, and (ii) to apply these skills in the construction of a series of molecular chimeras between SIV and HIV-1. Basic training will be accomplished through pertinent didactic coursework, participation in specialized courses covering such topics as advanced in situ hybridization, active benchwork in the laboratory, and regular consultation and interaction with her co-sponsors. The goal of the research proposed for Phase I is the development of a model of HIV-1 infection in non-human primates using SIV/HlV-1 molecular chimera. During the pre-Phase I portion of her training, Dr. Lewis has successfully constructed an SIV/HlV-1 prototype chimera (SHIV) composed of a background SIV with high replicative ability in which the envelope gene is provided by HIV-1. In vitro viability and infectivity for pig-tailed macaques has been demonstrated. The goal of the construction of further chimeras in Phase I is to increase the replicative ability of the chimera by restoring the HIV-1 vpu open reading frame and restoring the SIV tat reading frame and the associated splice junction. Phase I will last 2 years. Completion of Phase I will be determined by completion of Phase I research as described above as well as the successful completion of the requirements for the Ph.D. degree as decreed by the Ohio State University. The specific aims for Phase II research are: (i) to construct SHIV chimeras with divergent HIV-1 envelope genes; (ii) to construct SHIV chimeras with an HIV-1 reverse transcriptase; and (iii) to test additional SHIV chimeras in the pig-tailed macaque model. Phase II is an expansion of skills and ideas developed during Phase I and will last 2 years.

本医师描述了 Anne Lewis 医生的培训计划 科学家奖（K11）申请。该计划旨在提供博士。 刘易斯拥有从分子水平研究病毒发病机制的技能 以使她最终成为一名独立调查员。 刘易斯博士是一位经过委员会认证的兽医病理学家，最近 返回研究生院攻读博士学位。实验学位 俄亥俄州立大学兽医病理学系病理学 大学。她由菲利普·约翰逊博士和保罗博士共同赞助 斯特罗姆伯格。 刘易斯博士培训计划第一阶段的具体目标是： (i) 获得病毒学、组织培养和分子生物学方面的基本培训 生物学，以及（ii）将这些技能应用于构建一系列 SIV 和 HIV-1 之间的分子嵌合体。基础训练将是 通过相关的教学课程、参与 涵盖高级现场等主题的专业课程 杂交、实验室中的主动工作台工作以及常规 与她的共同发起人进行协商和互动。的目标 拟议的第一阶段研究是开发 HIV-1 模型 使用 SIV/HIV-1 分子嵌合体感染非人类灵长类动物。期间 在她培训的第一阶段前部分，刘易斯博士成功地 构建了由背景组成的SIV/HIV-1原型嵌合体（SHIV） 具有包膜基因的具有高复制能力的SIV HIV-1。猪尾猕猴的体外活力和感染性 已被证明。进一步构建嵌合体的目标 第一阶段是通过恢复来增加嵌合体的复制能力 HIV-1 vpu开放阅读框和恢复SIV tat阅读框 和相关的剪接点。第一阶段将持续2年。完成 第一阶段的研究将由第一阶段研究的完成来确定： 上述以及成功完成要求 对于博士学位。俄亥俄州立大学颁发的学位。 II 期研究的具体目标是： (i) 构建 SHIV 具有不同 HIV-1 包膜基因的嵌合体； (ii) 构建SHIV 具有 HIV-1 逆转录酶的嵌合体； (iii) 测试额外的 猪尾猕猴模型中的 SHIV 嵌合体。第二阶段是扩建 第一阶段开发的技能和想法将持续两年。