Annotation and Comparative Genomic Analysis of Cryptosporidium baileyi

贝氏隐孢子虫注释及比较基因组分析

• 批准号: 9067130
• 负责人: Shelton Griffith
• 金额: $ 1.95万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9067130
• 关键词: Africa; Animal Model; Animals; Asia; Bacteria; Basic Science; Bioinformatics; Birds; Cattle; Cause of Death; Cessation of life; Chickens; Child; Chronic; Clinical; Comparative Genomic Analysis; Computer software; Cryptosporidiosis; Cryptosporidium; Cryptosporidium parvum; Data; Diagnosis; Diarrhea; Disease; Epidemiology; Family suidae; Gene Expression; Gene Expression Profile; Gene Family; Genes; Genome; Gnotobiotic; Goals; Growth and Development function; Human; Immune response; Immunocompromised Host; In Vitro; Individual; Infant; Infection; Intervention; Investigation; Lead; Malnutrition; Microscopic; Modeling; Nutritional; Organism; Parasites; Pharmacotherapy; Prevention; Reading; Research; Research Infrastructure; Research Personnel; Risk; Rotavirus; Scientist; Shigella; Study models; Synteny; Testing; Toddler; Training; Vaccines; Work; base; comparative; egg; enterotoxigenic Escherichia coli; gastrointestinal; genome annotation; genome sequencing; low income country; novel; pathogen; public health relevance; tool; transcriptome; transcriptome sequencing; trend; wasting

 DESCRIPTION (provided by applicant): Diarrhea is one of the leading causes of death among children under five globally. More than one in ten child deaths - about 800,000 each year - is due to diarrhea. Today, only 44% of children with diarrhea in low- income countries receive the recommended treatment, and limited trend data suggest that there has been little progress since 2000. In 2013, a massive clinical and epidemiological study1 involving 22,500 children from Africa and Asia revealed - unexpectedly - that the protozoan parasite Cryptosporidium is one of four pathogens responsible for the lion's share of severe diarrhea in infants and toddlers. Vaccines and treatments are already available or fast being developed for three of the four pathogens identified: rotavirus, Shigella bacteria and enterotoxigenic Escherichia coli. But for 'crypto', there is no fully effective drug treatment or vaccine, and the basic research tools ad infrastructure needed to discover, evaluate and develop such interventions are mostly lacking. Cryptosporidium is a zoonotic apicomplexan protist parasite that causes gastrointestinal illness with diarrhea in humans and animals. However, the disease is most serious in children and immunocompromised individuals, especially malnourished children, where the infection can aggravate poor nutritional conditions, lead to impaired immune response, chronic infection and long-term negative impact on growth and development. Cryptosporidium parasites are found globally. In the US, an estimated 748,000 cases of cryptosporidiosis occur each year. My long-term goal is to help with the treatment/prevention of Cryptosporidium infections. To achieve this goal I will use bioinformatics to help test the hypothesis that C. baileyi may be a suitable animal model for the human-infecting C. parvum and C. hominis. A comparative genomic analysis of C. baileyi as well as comparative transcriptional profiles will be performed. A C. baileyi model is important because this species can complete its lifecycle in experimentally tractable chicken eggs unlike other species which require cattle or gnotobiotic pigs e.g. C. hominis and C. parvum. In vitro culture is not yet available for any species. To test my hypothesis about the model, I will conduct the first ever annotation of C. baileyi, compare its genome annotation to human-infecting species of Cryptospordium and use RNA-Seq data generated from C. baileyi to compare the gene expression to that of C. parvum (the only other organism gene expression data is available for). My results will contribute to a new animal model for Cryptosporidium.

 描述（由申请人提供）：腹泻是全球五岁以下儿童死亡的主要原因之一。超过十分之一的儿童死亡-每年约80万-是由于腹泻。今天，低收入国家只有44%的腹泻儿童接受了推荐的治疗，有限的趋势数据表明，自2000年以来几乎没有进展。2013年，一项涉及22，500名非洲和亚洲儿童的大规模临床和流行病学研究1意外地发现，原生动物寄生虫隐孢子虫是导致婴幼儿严重腹泻的四种病原体之一。针对已确定的四种病原体中的三种：轮状病毒、志贺氏菌和产肠毒素大肠杆菌，疫苗和治疗方法已经可用或正在快速开发中。但对于“加密”来说，没有完全有效的药物治疗或疫苗，并且大多缺乏发现，评估和开发此类干预措施所需的基础研究工具和基础设施。隐孢子虫是一种人畜共患的顶复门原生寄生虫，可引起人类和动物的胃肠道疾病和腹泻。然而，这种疾病在儿童和免疫功能低下的人中最为严重，特别是营养不良的儿童，感染会加剧营养不良状况，导致免疫反应受损、慢性感染和对生长发育的长期负面影响。隐孢子虫寄生虫在全球范围内发现。在美国，估计每年发生748，000例隐孢子虫病。我的长期目标是帮助治疗/预防隐孢子虫感染。为了实现这一目标，我将使用生物信息学来帮助测试的假设，C。Baileyi可以是合适的动物， 人感染C. parvum和C.人类对C.进行Baileyi以及比较转录谱。梭baileyi模型是重要的，因为该物种可以在实验上易于处理的鸡蛋中完成其生命周期，而不像其他物种需要牛或无菌猪，例如C. hominis和C.小的体外培养尚未用于任何种属。为了验证我对这个模型的假设，我将对C语言进行有史以来的第一次注释。baileyi，将其基因组注释与人类感染的隐孢子虫物种进行比较，并使用从C. baileyi与C. parvum（唯一的其他生物基因表达数据是可用的）。本研究结果将为隐孢子虫的动物模型研究提供新的思路。