The Transmission Biology of Mycobacterium Tuberculosis

结核分枝杆菌的传播生物学

• 批准号: 10620780
• 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/10620780
• 关键词: 2019-nCoV; Aerosols; Air; Alveolus; Atmosphere; Bacillus; Base Excision Repairs; Biochemical Pathway; Biology; Breathing; COVID-19; CRISPR interference; Carbon; Cause of Death; Cell Nucleus; Cell physiology; Cells; Cessation of life; Chemicals; Clinical; Communicable Diseases; DNA Damage; Data; Deposition; Desiccation; Detection; Development; Diagnostic; Diameter; Discipline; Disease; Doctor of Philosophy; Dryness; Enzymes; Event; Exposure to; Gene Expression; Gene Silencing; Generations; Goals; Grant; Health Professional; Health Services Accessibility; Household; Human body; Hydration status; 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; Oxidative Stress Induction; Pathway interactions; Population; Positioning Attribute; Predisposition; Process; Pseudomonas; Recovery; Research; Research Training; Schools; Scientist; Secondary to; State Government; Streptococcus pneumoniae; Stress; Suspensions; Testing; Training; Transportation; Trehalose; Tuberculosis; Vaccination; Virus; Water; Work; aerosolized; 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 blocking; 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·布朗医学博士是韦尔大学传染病系的医学讲师。 纽约市的康奈尔医学院。他的研究兴趣集中在定义传播的生物学上 结核分枝杆菌。这项为期五年的培训拨款概述了技术、研究和专业精神。 开启独立学术生涯所需的目标。布朗博士曾接受过广泛的研究培训 在劳拉·L·基斯林的实验室做博士工作的有机化学家和化学生物学家。这 该提案扩展到微生物学、代谢组学和调控基因表达等领域。利用一种 这些学科的结合是研究生物系统分子的一种强有力的方法。 结核分枝杆菌传播生物学是一个非常有机会发现的领域。变速箱的发展 阻断疗法将对全球健康和死亡率产生深远影响。这项提案的研究目标是 识别细菌编码的决定因素，通过赋予空气中的生存能力，有利于成功传播。这个 PI将使实验室和临床结核分枝杆菌菌株暴露在风干压力下，并记录对新陈代谢的影响 和细胞的完整性。关于新陈代谢途径对生存的重要性的假设将得到检验 使用CRISPRi(聚类规则散布短回文重复干扰)基因沉默。