Population genomics of anthelmintic resistance in parasitic nematodes of livestock : Haemonchus contortus as a model system

家畜寄生线虫驱虫抗性的群体基因组学:捻转血矛线虫作为模型系统

基本信息

  • 批准号:
    RGPIN-2015-03976
  • 负责人:
  • 金额:
    $ 2.91万
  • 依托单位:
  • 依托单位国家:
    加拿大
  • 项目类别:
    Discovery Grants Program - Individual
  • 财政年份:
    2019
  • 资助国家:
    加拿大
  • 起止时间:
    2019-01-01 至 2020-12-31
  • 项目状态:
    已结题

项目摘要

The emergence of drug resistance to pests and pathogens is one of the major challenges of the 21st century. Parasitic nematodes are metazoan parasites that are of huge economic importance to the global and Canadian livestock industries and in which drug resistance is a major problem. Thelong term objective of my research program is to develop a comprehensive understanding of how livestock parasites become resistant to drugs (anthelmintics) and to apply this knowledge to improve surveillance and sustainable control. In this discovery grant project, I will apply population genomic approaches to investigate the genetic basis of anthelmintic drug resistance and the evolutionary processes leading to its emergence and spread using the small ruminant parasite Haemonchus contortus. This is an excellent study model since this parasite has widespread resistance to the major anthelmintic drug classes, has a high quality reference genome, has excellent population genetic tools and is one of the most experimentally tractable animal parasitic nematodes. It is also an important emerging disease problem for the Canadian sheep industry. This NSERC Discovery Grant renewal directly builds on my previous work and has the following specific objectives. Objective 1 will investigate the origin and spread of anthelmintic resistance. Deep sequencing approaches will be used to provide an unprecedented view of resistant and susceptible haplotype diversity at known, and candidate, drug resistance loci for the major broad spectrum anthelmintic drugs. The aim is to provide the first clear picture of the number of independent origins of resistance in different parts of the world and also to test the leading candidate resistance loci for evidence of selection and therefore relevance in the field. Objective 2 will undertake genome-wide scans to investigate signatures of selection in H. contortus field populations. The aim is to identify novel  drug resistance loci (as well as confirm or refute the importance of previously implicated candidate loci). This is an important aim since there is ample evidence that many important anthelmintic resistance loci remain to be discovered. Objective 3 will investigate whether interspecies hybridization leads to introgression of drug resistance loci between H. contortus and the closely related cattle parasite Haemonchus placei. The aim is to provide a proof-of-concept that drug resistance can be transferred between different parasitic nematode species in the field. This objective will also provide an additional novel approach to identify new drug resistance loci (based on the identification of "super invasive" introgressed loci). This program of research will provide an excellent opportunity to apply state-of-the-art population genomic approaches to an important practical problem that is of major significance to global food production.**
对害虫和病原体的耐药性的出现是21世纪的主要挑战之一。寄生线虫是对全球和加拿大畜牧业具有巨大经济重要性的后生动物寄生虫,其中耐药性是一个主要问题。我的研究项目的长期目标是全面了解家畜寄生虫如何对药物(驱虫药)产生耐药性,并将这些知识应用于改善监测和可持续控制。在这个发现资助项目中,我将应用群体基因组学方法来研究驱虫药耐药性的遗传基础,以及导致其出现和传播的进化过程,使用小型反刍动物寄生虫捻转血矛线虫。这是一个很好的研究模型,因为这种寄生虫对主要的驱虫药物类具有广泛的耐药性,具有高质量的参考基因组,具有优良的群体遗传工具,是实验上最易处理的动物寄生线虫之一。这也是加拿大养羊业的一个重要的新出现的疾病问题。这次NSERC发现补助金的更新直接建立在我以前的工作基础上,并有以下具体目标。目的1探讨驱虫药耐药性的起源和传播。深度测序方法将用于为主要广谱驱虫药的已知和候选耐药基因座提供前所未有的耐药和易感单倍型多样性视图。其目的是提供第一个清晰的图片的独立起源的抗性在世界不同地区的数量,并测试领先的候选抗性基因座的选择的证据,因此在field.Objective2将进行全基因组扫描,以调查选择在H。contortus现场种群。其目的是确定新的耐药基因座(以及确认或反驳先前涉及的候选基因座的重要性)。这是一个重要的目标,因为有足够的证据表明,许多重要的驱虫药抗性基因座仍有待发现。捻转血矛线虫和密切相关的牛寄生虫布氏血矛线虫。其目的是提供一个概念验证,即耐药性可以在田间不同的寄生线虫物种之间转移。这一目标还将提供一种额外的新方法来鉴定新的耐药基因座(基于鉴定“超侵入性”渗入基因座)。这项研究计划将提供一个极好的机会,将最先进的群体基因组方法应用于对全球粮食生产具有重大意义的重要实际问题。

项目成果

期刊论文数量(0)
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Gilleard, John其他文献

The presence of benzimidazole resistance mutations in Haemonchus placei from US cattle
  • DOI:
    10.1016/j.vetpar.2014.05.025
  • 发表时间:
    2014-08-29
  • 期刊:
  • 影响因子:
    2.6
  • 作者:
    Chaudhry, Umer;Miller, Melissa;Gilleard, John
  • 通讯作者:
    Gilleard, John

Gilleard, John的其他文献

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{{ truncateString('Gilleard, John', 18)}}的其他基金

Population genomics of ivermectin drug resistance in parasitic nematodes of livestock
家畜寄生线虫伊维菌素耐药性的群体基因组学
  • 批准号:
    RGPIN-2021-02489
  • 财政年份:
    2022
  • 资助金额:
    $ 2.91万
  • 项目类别:
    Discovery Grants Program - Individual
Population genomics of ivermectin drug resistance in parasitic nematodes of livestock
家畜寄生线虫伊维菌素耐药性的群体基因组学
  • 批准号:
    RGPIN-2021-02489
  • 财政年份:
    2021
  • 资助金额:
    $ 2.91万
  • 项目类别:
    Discovery Grants Program - Individual
Population genomics of anthelmintic resistance in parasitic nematodes of livestock : Haemonchus contortus as a model system
家畜寄生线虫驱虫抗性的群体基因组学:捻转血矛线虫作为模型系统
  • 批准号:
    RGPIN-2015-03976
  • 财政年份:
    2018
  • 资助金额:
    $ 2.91万
  • 项目类别:
    Discovery Grants Program - Individual
Population genomics of anthelmintic resistance in parasitic nematodes of livestock : Haemonchus contortus as a model system
家畜寄生线虫驱虫抗性的群体基因组学:捻转血矛线虫作为模型系统
  • 批准号:
    RGPIN-2015-03976
  • 财政年份:
    2017
  • 资助金额:
    $ 2.91万
  • 项目类别:
    Discovery Grants Program - Individual
Population genomics of anthelmintic resistance in parasitic nematodes of livestock : Haemonchus contortus as a model system
家畜寄生线虫驱虫抗性的群体基因组学:捻转血矛线虫作为模型系统
  • 批准号:
    RGPIN-2015-03976
  • 财政年份:
    2016
  • 资助金额:
    $ 2.91万
  • 项目类别:
    Discovery Grants Program - Individual
Population genomics of anthelmintic resistance in parasitic nematodes of livestock : Haemonchus contortus as a model system
家畜寄生线虫驱虫抗性的群体基因组学:捻转血矛线虫作为模型系统
  • 批准号:
    RGPIN-2015-03976
  • 财政年份:
    2015
  • 资助金额:
    $ 2.91万
  • 项目类别:
    Discovery Grants Program - Individual
Population genetics of parasitic nematodes of livestock; the spread of anthelmentic resistance and range expansion in Haemonchus spp
家畜寄生线虫的群体遗传学;
  • 批准号:
    371529-2009
  • 财政年份:
    2013
  • 资助金额:
    $ 2.91万
  • 项目类别:
    Discovery Grants Program - Individual
Population genetics of parasitic nematodes of livestock; the spread of anthelmentic resistance and range expansion in Haemonchus spp
家畜寄生线虫的群体遗传学;
  • 批准号:
    371529-2009
  • 财政年份:
    2012
  • 资助金额:
    $ 2.91万
  • 项目类别:
    Discovery Grants Program - Individual
Population genetics of parasitic nematodes of livestock; the spread of anthelmentic resistance and range expansion in Haemonchus spp
家畜寄生线虫的群体遗传学;
  • 批准号:
    371529-2009
  • 财政年份:
    2011
  • 资助金额:
    $ 2.91万
  • 项目类别:
    Discovery Grants Program - Individual
Population genetics of parasitic nematodes of livestock; the spread of anthelmentic resistance and range expansion in Haemonchus spp
家畜寄生线虫的群体遗传学;
  • 批准号:
    371529-2009
  • 财政年份:
    2010
  • 资助金额:
    $ 2.91万
  • 项目类别:
    Discovery Grants Program - Individual

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开发小分子代谢酶抑制剂作为广谱驱虫药
  • 批准号:
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Population genomics of anthelmintic resistance in parasitic nematodes of livestock : Haemonchus contortus as a model system
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