The Transmission Biology of Mycobacterium Tuberculosis

项目概要/摘要 Christopher Brown 医学博士、哲学博士是威尔医院传染病科的医学讲师 纽约市康奈尔医学院。他的研究兴趣集中于定义传播生物学 在结核分枝杆菌中。这项为期五年的培训补助金概述了技术、研究和专业精神 开展独立学术生涯所需的目标。布朗博士作为一名研究人员接受过广泛的研究培训 有机化学家和化学生物学家，在 Laura L. Kiessling 实验室攻读博士学位。这个 该提案扩展到微生物学、代谢组学和调控基因表达领域。利用一个 这些学科的结合是对生物系统进行分子研究的强大方法。 结核分枝杆菌传播生物学是一个充满大量发现机会的领域。变速器的开发 阻断疗法将对全球健康和死亡率产生深远影响。本提案的研究目标 的目的是识别细菌编码的决定因素，这些因素通过赋予空气中的生存能力而有利于成功传播。的 PI 将实验室和临床的 Mtb 菌株暴露于空气干燥压力下，并记录对代谢的影响 和细胞完整性。关于代谢途径对于生存的重要性的假设将得到检验 使用 CRISPRi（成簇规则散布短回文重复干扰）基因沉默。

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.