Mycobacterial Determinants of Cavitation & Transmission

描述（由申请人提供）：德容博士先前有国际研究经验，最近在斯坦福大学完成了传染病临床培训。为了促进她转变为一名国际研究科学家，她现在建议将流行病学的联合收割机教学培训与一个假设驱动的项目结合起来，该项目旨在更好地了解结核病传播的决定因素。这项工作将在冈比亚一个完善的研究环境中进行，并由具有互补专业知识的教师指导。 在连续三个夏天，她将获得荷兰健康科学研究所流行病学硕士学位。该课程提供了流行病学研究的原则和实践的全面调查，并专门构建为在此期间传播，并与独立的研究项目相结合。 她将从事的研究项目测试了这样一种假设，即分枝杆菌菌株之间的遗传差异有助于肺空洞和人与人之间传播的可变速率。众所周知，宿主和环境因素极大地影响了M感染的临床表现和后果。结核然而，人们对分枝杆菌菌株之间差异的后果知之甚少。候选人迄今为止在分子流行病学实验室工作所获得的专业知识和她将在课堂上学习的临床流行病学课程的结合将为她提供在该领域正式解决这一问题的机会。具体来说，她将在冈比亚至少呆两年，量化M临床分离株的倾向。结核病可引起空洞并传播给家庭接触者。随后，在斯坦福大学，她将使用基于DNA微阵列的比较基因组方法来寻找这些细菌倾向的遗传相关性。 虽然承诺这些活动将对结核病的全球负担产生重大影响是冒昧的，但拟议的项目可能会成为她转变为专注于国际转化临床研究的独立医生科学家的工具。

DESCRIPTION (provided by applicant): Dr. de Jong has prior international research experience and recently completed her clinical training in infectious diseases at Stanford University. In order to foster her transition into an international research scientist, she now proposes to combine didactic training in epidemiology with a hypothesis driven project designed to better understand the determinants of tuberculosis transmission. This work will be conducted in a well-established research setting in the Gambia and mentored by faculty with complementary expertise. Over three consecutive summers she will obtain a Masters degree in epidemiology at the Netherlands Institute for Health Sciences. This curriculum provides a comprehensive survey of the principles and practices of epidemiologic research and is specifically structured to be spread over this period and integrated with an independent research project. The research project that she will pursue tests the hypothesis that genetic differences between mycobacterial strains contribute to variable rates of pulmonary cavitation and person- to- person transmission. It is well established that host and environmental factors greatly impact the clinical manifestations and consequences of infection with M. tuberculosis. However, little is known about the consequences of differences between mycobacterial strains. The combination of expertise the candidate has gained to date working in a molecular epidemiology laboratory and the clinical epidemiologic lessons that she will learn in the classroom will provide her the opportunity to formally address this issue in the field. Specifically, she will spend at least two years in The Gambia quantifying the propensity of clinical isolates of M. tuberculosis to cause cavitation and be transmitted to household contacts. Subsequently, at Stanford University, she will use a DNA microarray based comparative genomic approach to seek genetic correlates of these bacterial propensities. While it would be presumptuous to promise that these activities will have a major impact on the global burden of tuberculosis, it is likely that the proposed project will serve as a vehicle for her transition into an independent physician scientist focused on international translational clinical investigation.