Doctoral Dissertation Research: The Zoonotic Origins of Tuberculosis Infection in the Pre-contact Americas

博士论文研究：接触前美洲结核病感染的人畜共患起源

• 批准号: 1945812
• 负责人: Anne Stone
• 金额: $ 3.14万
• 依托单位: Arizona State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1945812&HistoricalAwards=false
• 关键词: Doctoral; Dissertation; Research; Zoonotic; Origins

Mycobacterium tuberculosis has a global distribution and infects over a million new people each year. In the pre-contact Americas, tuberculosis (TB) infection was caused by a strain that is found today in seals and sea lions. This doctoral dissertation project investigates how a zoonotic strain of TB adapted to humans as a primary host and spread across the Americas. Throughout the project, undergraduate students at Arizona State University will be trained in genomic lab work and analysis, and the resulting datasets will be used to create undergraduate-level workshops. The research team will demonstrate an equitable international collaboration by fostering mutual understanding and inclusivity among affiliated parties, thereby facilitating long-term, innovative, and productive relationships between institutions.The Mycobacterium tuberculosis complex (MTBC) refers to a group of similar pathogens that cause TB infection in humans and animals. Genomes extracted from archaeological remains show that zoonotic lineages were responsible for human TB infections in the past. Most TB infections in humans today, however, are caused by M. tuberculosis, the human-adapted MTBC lineage. The evolutionary steps of an animal-adapted pathogen becoming a human-adapted pathogen are not entirely understood. The researchers will draw comparisons between modern and ancient MTBC genomes to understand better how zoonotic lineages of TB adapt to humans as primary hosts. Ancient MTBC genomes will be extracted from archaeological skeletons. The research team focuses on a densely populated city and trade epicenter to determine the breadth of genomic diversity of ancient circulating MTBC strains, some of which were likely imported through long-distance trade. As human populations expand and the interface between humans and wildlife narrows, understanding the genomic underpinnings of zoonotic transmission dynamics will inform public health surveillance measures. The results of these comparisons will help frame future epidemiological, evolutionary biology, and infectious disease research.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

结核分枝杆菌具有全球分布，每年感染超过100万新人。在接触前美洲，结核病（TB）的感染是由今天在海豹和海狮中发现的菌株引起的。该博士学位论文项目调查了TB的人畜共患菌株如何适应人类作为主要宿主，并在整个美洲中传播。在整个项目中，亚利桑那州立大学的本科生将接受基因组实验室工作和分析的培训，由此产生的数据集将用于创建本科级别的研讨会。研究小组将通过促进附属方之间的相互理解和包容性来展示公平的国际合作，从而促进机构之间的长期，创新和生产性关系。结核病结核病（MTBC）是指引起人类和动物的TB感染的一组类似病原体。从考古遗物中提取的基因组表明，人畜共患病谱系是造成人类结核病感染的原因。然而，当今人类的大多数结核病感染是由结核分枝杆菌（人类适应的MTBC谱系）引起的。动物适应的病原体成为人适应的病原体的进化步骤尚未完全了解。研究人员将在现代和古代MTBC基因组之间进行比较，以更好地了解结核病的人畜共患病如何适应人类作为主要宿主。古老的MTBC基因组将从考古骨骼中提取。研究小组专注于人口稠密的城市和贸易震中，以确定古代循环MTBC菌株的基因组多样性的广度，其中一些可能是通过长距离贸易进口的。随着人群的扩大和人类与野生动植物之间的界面的扩大，了解人畜共患透射动态的基因组基础将为公共卫生监视措施提供依据。这些比较的结果将有助于构建未来的流行病学，进化生物学和传染病研究。该奖项反映了NSF的法定任务，并使用基金会的知识分子优点和更广泛的影响评估标准，被认为值得通过评估来提供支持。