COLLABORATIVE RESEARCH: GENOMIC DETERMINANTS OF PATHOGENICITY AND SUSCEPTIBILITY IN AN EMERGING FUNGAL PATHOGEN AND ITS VERTEBRATE HOSTS

合作研究：新兴真菌病原体及其脊椎动物宿主的致病性和易感性的基因组决定因素

• 批准号: 1640302
• 负责人: Matthew Settles
• 金额: $ 4.4万
• 依托单位: University of California-Davis
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1640302&HistoricalAwards=false
• 关键词: COLLABORATIVE; RESEARCH; GENOMIC; DETERMINANTS; PATHOGENICITY

Amphibians around the world are disappearing at an alarming rate. Many recent declines have been caused by a deadly chytrid fungus called Batrachochytrium dendrobatidis (Bd). Bd has recently spread around the world and infects hundreds of amphibian species. This project focuses on understanding the interaction between the Bd pathogen and its amphibian hosts. Specifically the investigators will learn 1) why some amphibian species are devastated by Bd while others are not harmed and 2) why some strains of Bd are more deadly than others. The investigators will conduct an integrative and worldwide study of numerous Bd isolates and a diversity of frog species. Results from this project will help guide conservation efforts be targeted to the most vulnerable species and to areas where Bd will have the most devastating impact. Further the general understanding of host-pathogen interactions resulting from this project can be applied to other systems where wildlife are threatened with new emerging diseases. The project also provides training opportunities for undergraduate and graduate students, with a focus on broadening participation of underrepresented groups. In addition to scientific research, the project will provides education about biodiversity and conservation to the public and local public elementary school children through popular press publications, museum exhibits, and an outreach event called "Save the Frogs Day". The researchers in this project have taken genetic, genomic, immunological, and organismal approaches to accomplish their objectives. First, they will use a comparative approach to identify genomic variations in 60 Bd isolates gathered from around the world that vary in infectivity towards various amphibian hosts. Second, they will study variations in in vitro growth phenotypes that they propose directly relate to infectivity. Last, they will examine in vivo and cell culture-based phenotypes, in parallel with host tissue profiling. A key aspect of the third goal is that the applicants have selected 6 congeneric amphibian host pairs (2 species in each of three different genera) that vary in susceptibility to Bd. They will utilize Illumina-based sequencing techniques to obtain genome-wide association studies of the phenotypes of interest. In vivo infection phenotypes such as Bd burden under the common garden conditions tested will be coupled with transcriptomic analysis of host gene expression to evaluate differential responses by susceptible/tolerant hosts. To address this important problem, the investigators have blended evolutionary, ecological and physiological perspectives and this integrative approach promises to bring new insight into this field.

世界各地的两栖动物正在以惊人的速度消失。最近许多数量的下降都是由一种致命的壶菌引起的，这种壶菌叫做Batrachochytrium dendroatidis （Bd）。Bd最近在世界各地蔓延，感染了数百种两栖动物。本项目的重点是了解Bd病原体与其两栖宿主之间的相互作用。具体来说，研究人员将了解1)为什么一些两栖动物物种被Bd摧毁，而另一些却没有受到伤害；2)为什么一些Bd菌株比其他菌株更致命。研究人员将对大量的蛙类分离株和蛙类多样性进行综合和全球范围的研究。这个项目的结果将有助于指导保护工作针对最脆弱的物种和最具破坏性影响的地区。此外，该项目对宿主-病原体相互作用的一般理解可以应用于野生动物受到新出现疾病威胁的其他系统。该项目还为本科生和研究生提供培训机会，重点是扩大代表性不足群体的参与。除了科学研究外，该项目还将通过流行的新闻出版物、博物馆展览和名为“拯救青蛙日”的外展活动，向公众和当地公立小学的孩子们提供有关生物多样性和保护的教育。该项目的研究人员采用了遗传学、基因组学、免疫学和有机体方法来实现他们的目标。首先，他们将使用一种比较方法来鉴定从世界各地收集的60种Bd分离株的基因组变异，这些分离株对各种两栖动物宿主的传染性各不相同。其次，他们将研究与传染性直接相关的体外生长表型的变化。最后，他们将检查体内和细胞培养为基础的表型，与宿主组织分析并行。第三个目标的一个关键方面是，申请人选择了6对对Bd易感性不同的同源两栖动物宿主（三个不同属各2种）。他们将利用基于illumina的测序技术获得感兴趣表型的全基因组关联研究。体内感染表型，如在普通花园条件下测试的Bd负担，将与宿主基因表达的转录组学分析相结合，以评估易感/耐受宿主的差异反应。为了解决这一重要问题，研究人员将进化论、生态学和生理学的观点结合起来，这种综合方法有望为这一领域带来新的见解。