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: 1354241
• 负责人: Erica Rosenblum
• 金额: $ 39.5万
• 依托单位: University of California-Berkeley
• 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 2018-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1354241&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。最近的许多下降是由一种名为树突巴氏杆菌(Bd)的致命壶菌引起的。BD最近在世界各地传播，感染了数百种两栖动物。这个项目的重点是了解Bd病原体与其两栖宿主之间的相互作用。具体地说，研究人员将了解1)为什么一些两栖动物物种被Bd摧毁，而另一些没有受到伤害，以及2)为什么Bd的某些品系比其他品系更致命。研究人员将对众多Bd分离株和不同种类的青蛙进行综合性和世界性的研究。该项目的结果将有助于指导针对最脆弱物种和Bd将产生最具破坏性影响的地区的保护工作。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，该项目还将通过流行的新闻出版物、博物馆展品和名为“拯救青蛙日”的外展活动，向公众和当地公立小学儿童提供关于生物多样性和保护的教育。该项目的研究人员采取了遗传、基因组、免疫学和有机学的方法来实现他们的目标。首先，他们将使用比较的方法来识别从世界各地收集的60个Bd分离株的基因组变异，这些分离株对不同的两栖动物宿主具有不同的感染力。其次，他们将研究他们提出的与传染性直接相关的体外生长表型的变异。最后，他们将检查体内和基于细胞培养的表型，同时检查宿主组织的特征。第三个目标的一个关键方面是，申请者选择了6对对Bd易感性不同的同类两栖动物宿主对(三个不同属中的每一个都有2个物种)。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负担，将与宿主基因表达的转录转录分析相结合，以评估敏感/耐受宿主的差异反应。为了解决这一重要问题，研究人员融合了进化论、生态学和生理学的观点，这种综合的方法有望为这一领域带来新的见解。