The Transmission Biology of Mycobacterium Tuberculosis

结核分枝杆菌的传播生物学

• 批准号: 10436357
• 负责人: Christopher David Brown
• 金额: $ 19.49万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-22 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10436357
• 关键词: 2019-nCoV; Aerosols; Air; Alveolus; Atmosphere; Bacillus; Base Excision Repairs; Biochemical Pathway; Biology; Breathing; COVID-19; CRISPR interference; Caliber; Carbon; Cause of Death; Cell Nucleus; Cell physiology; Cells; Cessation of life; Chemicals; Clinical; Communicable Diseases; DNA Damage; Data; Deposition; Desiccation; Detection; Development; Diagnostic; Discipline; Disease; Doctor of Philosophy; Enzymes; Event; Exposure to; Gene Expression; Gene Silencing; Generations; Goals; Grant; Health Professional; Health Services Accessibility; Household; Human body; Immunity; Immunologic Surveillance; Improve Access; Incidence; Individual; Infection; Influenza; Inhalation; Investigation; Laboratories; Life Cycle Stages; Lower respiratory tract structure; Lung; Maps; Medicine; Metabolic; Metabolic Pathway; Metabolism; Methods; Microbiology; Molecular; Mycobacterium tuberculosis; New York City; Nucleotide Biosynthesis; Nucleotides; Organism; Oxidative Stress; Pathway interactions; Population; Positioning Attribute; Predisposition; Process; Pseudomonas; Recovery; Rehydrations; Research; Research Training; Schools; Scientist; Secondary to; State Government; Streptococcus pneumoniae; Stress; Stress Tests; Suspensions; Testing; Training; Transportation; Trehalose; Tuberculosis; Vaccination; Virus; Water; Work; biological systems; career; clastogen; comparative; global health; insight; instructor; interest; international health organization; medical schools; metabolomics; mortality; novel; novel strategies; oxidative damage; particle; pathogen; repaired; respiratory pathogen; response; success; transmission process; treatment program; vaccine candidate

PROJECT SUMMARY/ABSTRACT Christopher Brown MD, PhD is an Instructor of Medicine in the division of infectious diseases at Weill- Cornell Medical College in New York City. His research interests focus on defining the biology of transmission in Mycobacterium tuberculosis. This five-year training grant outlines technical, research and professionalism goals needed to launch an independent academic career. Dr. Brown has extensive research training as an organic chemist and chemical biologist from his doctoral work in the laboratory of Laura L. Kiessling. This proposal expands into the fields of microbiology, metabolomics and regulated gene expression. Utilizing a combination of these disciplines is a powerful method for the molecular interrogation of biological systems. Mtb transmission biology is a field of substantial opportunity for discovery. Development of a transmission blocking therapy would have a profound impact on global health and mortality. The research goal of this proposal is to identify bacterially-encoded determinants that favor successful transmission by imparting survival in air. The PI will expose laboratory and clinical strains of Mtb to air-drying stress and document the effects on metabolism and cellular integrity. Hypotheses regarding the essentiality of metabolic pathways for survival will be tested using CRISPRi (clustered regularly interspersed short palindromic repeat interference) gene silencing.

项目摘要/摘要 克里斯托弗·布朗（Christopher Brown）医学博士是威尔（Weill）传染病的医学教练 纽约市的康奈尔医学院。他的研究兴趣着重于定义传播的生物学 在结核分枝杆菌中。这项五年培训赠款概述了技术，研究和专业精神 启动独立学术职业所需的目标。布朗博士接受了广泛的研究培训 他在Laura L. Kiessling实验室的博士学位工作的有机化学家和化学生物学家。这 建议扩展到微生物学，代谢组学和调节基因表达的领域。利用一个 这些学科的组合是生物系统分子询问的有力方法。 MTB传输生物学是一个实质性发现的领域。传输的发展 阻止治疗将对全球健康和死亡率产生深远的影响。该提议的研究目标 是确定通过在空气中传播生存的细菌编码决定因素，这些决定因素有利于成功传播。这 PI将使MTB的实验室和临床菌株暴露于空气压力，并记录对代谢的影响 和细胞完整性。将测试有关代谢途径生存的本质的假设 使用CRISPRI（群集定期散布的短腔重复干扰）基因沉默。