Structural and functional studies of M. tuberculosis type VII secretion

VII 型结核分枝杆菌分泌物的结构和功能研究

• 批准号: 8514500
• 负责人: Oren S Rosenberg
• 金额: $ 12.91万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-16 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8514500
• 关键词: ATP phosphohydrolase; Bacteria; Basic Science; Binding; Biochemical; Biochemical Genetics; Biological Assay; Biology; Cessation of life; Clinic; Clinical; Clinical Sciences; Communicable Diseases; Complement; Crystallography; Cytoplasmic Tail; DNA Sequence Rearrangement; Development; Electron Microscopy; Elements; Energy Metabolism; Engineering; Enzymes; Escherichia coli; Family; Fluorescence; General Hospitals; Genes; Genetic; Genetic Techniques; Genus Mycobacterium; Goals; Gram-Negative Bacteria; Gram-Positive Bacteria; Grant; Homologous Gene; Human; Hydrolysis; Individual; Infection; Knock-out; Laboratories; Length; Life; Modeling; Molecular; Mus; Mutation; Mycobacterium Infections; Mycobacterium tuberculosis; Nucleotides; Organism; Pathogenesis; Physicians; Plasmids; Play; Population; Process; Property; Proteins; Research; Research Personnel; Resources; Respiratory Tract Infections; Rest; Role; San Francisco; Scientist; Series; Shapes; Staging; Structure; Substrate Cycling; System; Testing; Tuberculosis; Vaccine Therapy; Virulence; Virulent; Work; base; biosafety level 3 facility; cellular imaging; design; experience; in vivo; interest; macrophage; meetings; microbial; mutant; novel therapeutics; novel vaccines; nucleotide analog; prevent; protein activation; research study; structural biology; thermophilic bacteria

Dr. Oren Rosenberg is an infectious disease physician with a background in structural biology. His objective in this current project is to combine his clinical and basic science interests by studying the structure and function of key virulence determinants in Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis. Through a series of specific aims that use a combined structural, biochemical and genetic approach, Dr. Rosenberg will examine the role of essential components in the type VII secretion system, which is known to be critical for the virulence of Mtb. The goal is to understand mycobacterial infection better so as to aid in the design of faster, cheaper, less toxic and more effective ways to prevent and treat tuberculosis. Additionally this proposal is designed to complement Dr. Rosenberg's prior laboratory experience and provide him with the requisite technical and intellectual background in microbial pathogenesis and structural biology to function as an independent investigator. A committee of physicians and scientists will oversee Dr. Rosenberg's progression towards independence. His scientific development will also be enriched through attendance at UCSF courses in pertinent topics, several seminar series, departmental retreats and national meetings. Dr. Rosenberg will develop a clinical specialization in tuberculosis and other respiratory infections through work at the tuberculosis clinic at San Francisco General Hospital. At the end of the granting period Dr. Rosenberg will be prepared to develop his own research and clinical agenda as an independent investigator in the basic biology of microbial pathogenesis.

Oren Rosenberg博士是一名具有结构生物学背景的传染病医生。他目前的项目目标是通过研究结核分枝杆菌（Mtb）关键毒力决定因子的结构和功能，将他的临床和基础科学兴趣结合起来。Rosenberg博士将通过一系列具体目标，结合结构、生化和遗传方法，研究VII型分泌系统中基本成分的作用，这是已知的对结核分枝杆菌毒力至关重要的。目标是更好地了解分枝杆菌感染，以便帮助设计更快、更便宜、毒性更小和更有效的方法来预防和治疗结核病。此外，该提案旨在补充Rosenberg博士之前的实验室经验，并为他提供微生物发病机理和结构生物学方面必要的技术和知识背景，以作为独立研究者。一个由医生和科学家组成的委员会将监督罗森博格博士走向独立。他的科学发展也将通过参加加州大学旧金山分校的相关主题课程、几个系列研讨会、部门务虚会和国家会议而得到丰富。Rosenberg博士将通过在旧金山总医院肺结核门诊的工作，发展肺结核和其他呼吸道感染的临床专业。在授权期结束时，Rosenberg博士将作为微生物发病机理基础生物学的独立研究者，准备发展他自己的研究和临床议程。