Mycobacterial Determinants of Cavitation & Transmission

描述(申请人提供)：De Jong博士有国际研究经验，最近在斯坦福大学完成了她的传染病临床培训。为了促进她向国际研究科学家的转变，她现在提议将流行病学的说教培训与一个旨在更好地了解结核病传播决定因素的假设驱动项目相结合。这项工作将在冈比亚成熟的研究环境中进行，并由具有互补专业知识的教员指导。 在连续三个夏天，她将在荷兰健康科学研究所获得流行病学硕士学位。本课程对流行病学研究的原理和实践进行了全面的调查，并专门设计成在这一时期进行，并与一个独立的研究项目相结合。 她将继续进行的研究项目验证了这样一个假设，即分枝杆菌菌株之间的遗传差异导致了肺空化和人际传播的不同比率。众所周知，宿主和环境因素极大地影响结核分枝杆菌感染的临床表现和后果。然而，人们对分枝杆菌菌株之间的差异的后果知之甚少。应聘者到目前为止在分子流行病学实验室工作获得的专业知识与她将在课堂上学到的临床流行病学课程相结合，将为她提供在实地正式解决这一问题的机会。具体地说，她将在冈比亚花至少两年的时间来量化结核分枝杆菌临床分离株引起空洞并传播给家庭接触者的倾向。随后，在斯坦福大学，她将使用基于DNA微阵列的比较基因组学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全球结核病负担产生重大影响是鲁莽的，但拟议的项目很可能成为她转变为一名专注于国际转化性临床研究的独立内科科学家的工具。

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.