A genome-wide analysis of parasitic fitness in the Dutch elm disease fungus Ophiostoma novo-ulmi

自20世纪世纪以来，荷兰榆树病（DED）连续两次大流行已造成10亿多榆树死亡。高度侵袭性的真菌Ophiostoma novo-ulmi是导致目前DED大流行的原因，并对北美分布最广的本土榆树物种美洲榆（Ulmus americana）的种群产生了巨大影响。了解导致DED的宿主-病原体相互作用的遗传基础是开发涉及操纵病原体或其宿主的控制方法的基础。这项研究的总体目标是鉴定、表征和操纵影响O.新乌尔米。更具体地说，我们正在靶向参与致病性的基因，以及控制DED真菌在宿主中发育时观察到的两种生长形式（酵母和菌丝体）之间过渡的基因。建议的研究利用的专业知识和资源，我们已经开发了多年的分析O。新乌尔米。这些措施包括：1）维护广泛收集的现场分离的DED真菌来自世界各地;适合度改变的novo-ulmi突变体; 3）在受控环境条件下鉴定毒性降低的突变体的接种程序; 4）在不同实验条件下监测DED真菌中基因表达的方法;和5）获得O.新乌尔米。我们将使用最新的基因组技术（包括下一代测序）在广泛的搜索基因，有助于使O。novo-ulmi这样一个成功的病原体。这项工作的重要意义在于，一旦决定O。novo-ulmi的鉴定和特征，它成为可能提出和开发新的方法来中断病原体的生命周期，以保护在北美的剩余榆树种群。

More than one billion elms have been killed by two successive pandemics of Dutch elm disease (DED) since the early 20th century. The highly aggressive fungus Ophiostoma novo-ulmi is responsible for the current DED pandemic and has had a dramatic impact on populations of Ulmus americana, the most widespread native elm species in North America. Understanding the genetic basis of the host-pathogen interaction leading to DED is basic to developing control methods involving manipulation of the pathogen or its host. The general objective of the proposed research is to identify, characterize and manipulate genes that contribute to overall parasitic fitness in O. novo-ulmi. More specifically, we are targeting genes involved in pathogenicity, as well as genes that control the transition between the two growth forms (yeast and mycelium) observed in the DED fungi when they develop in their host. The proposed research takes advantage of the expertise and resources we have developed over the years in the analysis of O. novo-ulmi. These include 1) maintenance of an extensive collection of field isolates of DED fungi from around the world; 2) recovery of O. novo-ulmi mutants with altered fitness; 3) inoculation procedures under controlled environmental conditions for identifying mutants with reduced virulence; 4) methods for monitoring gene expression in DED fungi under different experimental conditions; and 5) access to the full genome sequence of O. novo-ulmi. We will use the latest genomic techniques (including Next Generation Sequencing) in an extensive search for genes that contribute making O. novo-ulmi such a successful pathogen. The significance of the proposed work is that once genes that contribute to parasitic fitness of O. novo-ulmi are identified and characterized, it becomes possible to propose and develop new ways to interrupt the life cycle of the pathogen, in order to protect the remaining elm populations in North America.