Regulating the balance between resistance and infection

在项目A中提出的研究试图开发科学工具来表征调节免疫系统介导的防御和感染的建立或维持之间的平衡的分子机制。PI是分子微生物学和免疫学系(MMI)的主席克里斯汀·A·拜伦。提出的实验来自该系的助理教授沃尔特·J·阿尔特伍德、安德鲁·G·坎贝尔、劳伦特·布罗西和乔治·雅普。MMI是布朗大学最年轻的基础科学系。它正在将重点放在本申请中提出的方案主题上，以及抵抗微生物感染的天然机制的总体一般研究领域。MMI小组的兴趣赞扬了许多临床部门的研究。这个项目中的所有初级调查人员都将受益于行政核心中为教师和研究发展而提出的努力。计划中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。这项工作将在以下特定目标中推进：1.建立识别与神经病理学相关的JV病毒感染B细胞的早期事件的方法；2.使用新的分子方法表征乙肝病毒RNaseH酶的结构和功能；3.开发一种系统来关键地测试NK T细胞在对感染剂的反应中的功能；以及4.建立一种系统来表征作为弓形虫潜伏期和免疫病理学决定因素的MHC-I类表达的组织特异性调节。这些实验的产品和结果有望促进对感染期间有助于健康和疾病的基本分子事件的理解。此外，他们将通过发展这些初级研究人员，并为他们提供独特的新实验工具，用于其他正在推进和开发的项目，从而增强罗德岛在进一步国家研究支持方面的竞争力。

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.