Regulating the balance between resistance and infection

项目A中提出的研究旨在开发科学工具，以表征调节免疫系统介导的防御与感染建立或维持之间平衡的分子机制。PI是分子微生物学和免疫学（MMI）系主任克莉丝汀A。比龙。本系助理教授Walter J. Altwood、Andrew G.坎贝尔，劳伦特布罗赛，和乔治雅普。MMI是布朗大学最年轻的基础科学系。它正在开发一个重点在本申请中提出的方案主题，以及抵抗微生物感染的先天机制的整体一般研究领域。MMI集团的兴趣恭维在一些临床部门的研究。本项目中的所有初级研究人员都将受益于为行政核心的教师和研究发展所做的努力。计划的研究将利用并依赖于拟议的研究核心设施，包括转基因小鼠、流式细胞仪和共聚焦/成像实验室。本论文的工作将在以下几个方面进行：1.鉴定JV病毒（一种与神经病理学相关的因子）感染B细胞的早期事件的方法的建立，2。用新的分子方法表征B型肝炎病毒核糖核酸酶H酶的结构和功能，3。开发一种系统，以严格测试NK T细胞对感染因子的反应，以及4。构建一个系统，以表征组织特异性调节MHC I类表达作为弓形虫潜伏期和免疫病理学的决定因素。这些实验的产物和结果有望促进对感染期间促进健康和疾病的基本分子事件的理解。此外，他们将提高罗得岛的竞争力，通过发展这些初级研究人员，并为他们提供独特的新的实验工具，用于其他先进和发展中的项目特点的因素调节和治疗工具，以加强对感染的防御。

The studies proposed in PROJECT A seek to develop scientific tools to characterize molecular mechanisms regulating balance between defense mediated by the immune system and establishment or maintenance of infections. The PI is the chairperson of the Department of Molecular Microbiology and Immunology (MMI), Christine A. Biron. The experiments proposed are from Assistant Professors in the Department, Walter J. Altwood, Andrew G. Campbell, Laurent Brossay, and George Yap. MMI is the youngest of the basic science departments at Brown University. It is developing a focus on the programmatic theme presented in this application, and the overall general research area of innate mechanisms in resistance to microbial infections. The MMI group's interest compliment research in a number of clinical departments. All of the junior investigators in this project will benefit from the efforts proposed for faculty and research development in the administrative core. The studies planned will take advantage of and dependent upon the research core facilities proposed including the transgenic mouse, flow cytometric, and confocal/imaging laboratories. The work will be advanced in the following specific aims: 1. Establishment of Approaches to Identify Early Events in Infection of B cells by JV Virus, an Agent Associated with Neuropathology, 2. Characterization of the Structure and Function of the Hepatitis B Virus RNase H Enzyme Using a Novel Molecular Approach, 3. Development of a System to Critically Test the Function of NK T Cells in Responses to Infectious Agents, and 4. Construction of a System to Characterize Tissue-Specific Regulation of MHC Class I Expression as a Determinant of Latency and Immunopathology in Toxoplasma. The products and results of these experiments promise to advance understanding of basic molecular events contributing to health and disease during infections. Moreover, they will enhance Rhode Island's competitiveness for further national research support by developing these junior investigators and by providing them with unique new experimental tools for use in other advancing and developing projects characterizing the factors regulating and therapeutic tools for enhancing defense against infections.