Molecular Ecology Underlying Human Health and Disease: A Prototype Study

描述（由申请人提供）：项目概述：尽管人体细胞约占90%，但与人类相关的微生物对人体整体健康的贡献在很大程度上仍未知。研究人员现在开始研究这些微生物和它们的人类宿主之间复杂的相互作用。技术进步加上对这一与健康有关的研究新领域的兴趣增加，包括人类微生物组计划的创建，已经对各种生物过程产生了有趣的见解。在这个应用程序中，我将描述一个计划，以探索人类微生物组的遗传因素，对人类健康有影响。作为原理证明，我将描述一组实验，以确定土壤细菌群落中存在的抗生素抗性元素。然后，我将使用这些数据来识别人类微生物组中的同源耐药元素。除了丰富我们对抗生素耐药性遗传决定因素的知识外，这项工作还将作为应用宏基因组技术评估人类健康的一个模型。公共卫生相关性：生活在人类肠道和口腔中的细菌是一个人健康的主要决定因素。研究这些细菌的生化特性将有助于深入了解人类疾病。在这项工作中，我计划使用一种新的方法来鉴定与人类相关的细菌群落中赋予抗生素耐药性的基因。本应用程序中概述的方法将作为诊断和治疗与人体内存在的细菌有关的其他疾病的指南。

DESCRIPTION (provided by applicant): Project Summary: Despite making up approximately 90 percent of the cells in the human body, the contributions of human-associated microbes to overall human health remain largely unknown. Researchers are now beginning to study the complex interactions between these microbes and their human hosts. Technological advances coupled with an increased interest in this new frontier in health-related research, including the creation of the Human Microbiome Project, has already yielded interesting insight into diverse biological processes. In this application, I will describe a plan to probe the human microbiome for genetic elements that have implication for human health. As a proof of principle, I will describe a set of experiments to identify antibiotic resistance elements present in a community of soil bacteria. I will then use this data to identify homologous resistance elements within the human microbiome. In addition to enriching our knowledge of the genetic determinants of antibiotic resistance, this work will serve as a model for the application of metagenomic technology to the assessment of human health. Public Health Relevance: The bacteria that live in the human gut and mouth are major determinants in the health of a person. Studying the biochemical properties of these bacteria will give insight into human disease. In this work, I plan to use a new approach to identify genes within the human-associated bacterial community that confer antibiotic resistance. The methodology outlined in this application will serve as a guide for the diagnosis and treatment of other diseases linked to the bacteria present within people.