Regulating the balance between resistance and infection

项目A中提出的研究旨在开发科学工具来描述调节免疫系统介导的防御和建立或维持感染之间平衡的分子机制。PI是分子微生物学和免疫学（MMI）部门的主席，Christine A. Biron。提出的实验是由该系的助理教授Walter J. Altwood、Andrew G. Campbell、Laurent Brossay和George Yap提出的。MMI是布朗大学最年轻的基础科学系。它正在发展的重点是在本应用程序中提出的纲领性主题，以及对微生物感染的先天机制的总体一般研究领域。MMI小组的兴趣补充了许多临床部门的研究。这个项目的所有初级研究者都将受益于为行政核心的教员和研究发展所做的努力。计划的研究将利用并依赖于提出的研究核心设施，包括转基因小鼠、流式细胞术和共聚焦/成像实验室。这项工作将在以下几个具体目标上推进：2. JV病毒感染B细胞早期事件识别方法的建立乙型肝炎病毒RNase H酶结构和功能的新分子方法研究；开发一种系统来严格测试NK T细胞对感染因子的反应功能；构建一个系统来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的决定因素。这些实验的产品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，通过培养这些初级研究人员，并为他们提供独特的新实验工具，以用于其他先进和发展的项目，从而提高罗德岛州在进一步获得国家研究支持方面的竞争力，这些项目描述了增强感染防御的调节因素和治疗工具。

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.