The molecular mechanisms by which novel pathogens emerge

该项目将调查病原体进化新宿主范围的机制;尽管宿主范围的进化与野生动物疾病、农业和人类健康直接相关，但这些机制仍然知之甚少。绿僵菌是一种常见的、具有重要生态意义的昆虫病原真菌，是研究病原菌进化、致病机理和传染病的理想模式菌。这些真菌的密切相关的菌株独立地进化为广谱的通才（感染广泛的昆虫）或具有狭窄的特定宿主范围的专家（特定菌株仅感染蝗虫，蚱蜢，金龟子或其他特定昆虫群体）。一些多面手昆虫病原体也与植物根形成有益的关联。本研究将对4个通用型绿僵菌菌株和7个专用型绿僵菌菌株的基因组多样性和基因表达进行分析，并结合生物信息学分析和假设驱动的候选基因实验，以确定：1）调控和执行感染过程的基因的数量、性质和网络; 2）控制毒力、宿主范围特异性和宿主转换的因素; 3）工程改造病原体性能以实现昆虫害虫的环境良性管理的关键目标，以及4）开发用于研究随进化时间的突变率的易处理模型。这项研究的重点是专家和通才宿主范围之间的遗传基础的过渡将提供一个急需的模型，了解新的疾病的演变。最后，这个项目是优秀的研究培训，因为它使学生接触到基因组学，生物信息学，分子生物学，微生物学，显微镜和宿主病原体生物学和进化的基本科学原理。除了培训一名博士后助理和两名研究生外，这项研究还将为本科生提供研究机会，其中包括来自代表性不足群体的六名学生;研究活动还将用于为各种课堂项目制定课程计划。

This project will investigate the mechanisms by which pathogens evolve new host ranges; despite the direct relevance of host-range evolution to wildlife disease, agriculture, and human health, these mechanisms are still poorly understood. The common, ecologically important and widely studied insect-pathogenic fungus Metarhizium is an ideal model for studying the evolution of pathogens, pathogenesis and infectious disease. Closely related strains of these fungi have independently evolved as either broad-spectrum generalists (infecting a broad range of insects) or as specialists with narrow, specific host ranges (with particular strains infecting only locusts, grasshoppers, scarab beetles, or other particular insect groups). Some of the generalist insect pathogens also form beneficial associations with plant roots. Atlases of genomic diversity and gene expression will be assembled for four generalist and seven specialist Metarhizium strains, and coupled with bioinformatic analysis and hypothesis-driven experiments on select candidate genes, to determine: 1) the number, nature and networking of genes that regulate and execute infection processes; 2) the factors controlling virulence, host-range specificity and host-switching; 3) key targets for engineering alterations of pathogen performance for environmentally benign management of insect pests, and 4) development of a tractable model for studying mutation rates over evolutionary time. The focus of this research on the genetic basis of transitions between specialist and generalist host ranges will provide a much-needed model for understanding the evolution of new diseases. Finally, this project is excellent for research training as it exposes students to genomics, bioinformatics, molecular biology, microbiology, microscopy and fundamental scientific principles of host-pathogen biology and evolution. In addition to training a postdoctoral associate and two graduate students, this study will provide research opportunities for undergraduate students, including six from underrepresented groups; research activities will also be used to develop lesson plans for various classroom projects.