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: 1354202
• 负责人: Matthew Settles
• 金额: $ 7万
• 依托单位: Regents of the University of Idaho
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1354202&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。最近的许多下降都是由一种名为Batrachochytrium dendrobatium（Bd）的致命壶菌引起的。最近，Bd已经在世界范围内传播，并感染了数百种两栖动物。该项目的重点是了解Bd病原体与其两栖类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，而其他物种没有受到伤害，2）为什么Bd的某些菌株比其他菌株更致命。研究人员将对许多Bd分离株和多种青蛙物种进行综合性的全球研究。该项目的结果将有助于指导保护工作，以最脆弱的物种和Bd将产生最具破坏性影响的地区为目标。此外，本项目对宿主-病原体相互作用的一般理解可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”的外联活动，向公众和当地公立小学的儿童提供有关生物多样性和保护的教育。该项目的研究人员采取了遗传学、基因组学、免疫学和生物学方法来实现他们的目标。首先，他们将使用比较方法来确定从世界各地收集的60个Bd分离物中的基因组变异，这些分离物对各种两栖动物宿主的感染性不同。其次，他们将研究他们提出的与感染性直接相关的体外生长表型的变化。最后，他们将检查体内和基于细胞培养的表型，同时进行宿主组织分析。第三个目标的一个关键方面是申请人已经选择了6个同源两栖动物宿主对（三个不同属中的每一个中的2个物种），其对Bd的易感性不同。他们将利用基于Illumina的测序技术来获得感兴趣的表型的全基因组关联研究。体内感染表型，如在测试的常见花园条件下的Bd负荷，将与宿主基因表达的转录组学分析相结合，以评价易感/耐受宿主的差异反应。为了解决这个重要的问题，研究人员已经融合了进化，生态和生理的角度，这种综合的方法有望为这一领域带来新的见解。