Identification of drug resistance genes in Fasciola hepatica using a combined in vitro phenotyping and pooled genotyping approach

肝片吸虫，一种常见的肝吸虫，是英国羊和牛患病和生产损失的主要原因，农业实践和气候的变化正在导致患病率上升，并向英国的新地区传播。为了控制肝吸虫，我们依赖于反复使用驱虫药（杀虫剂），特别是三氯咪唑，现在有报道称其广泛耐药。令人担忧的是，随着农民转向其他药物，如closantel，这些目前在大多数情况下有效的药物现在将出现耐药性。该项目的目的是使用体外方法筛选对这些替代杀虫剂产生耐药性的寄生虫，并从遗传学上确定哪些基因起作用，以便我们能够更好地了解寄生虫如何产生耐药性，同时也能够通过向农民提供关于使用驱虫药的最佳实践建议，发现并预防多种药物耐药性的发展。除了发展高水平的基因组和生物信息学技能外，您还将直接与农民一起工作。这个项目非常适合合格的兽医，或对兽医科学感兴趣的生物学毕业生，希望发展先进的下一代测序技能。BBSRC的战略重点包括强调“农业和粮食安全”，特别是：提高英国生产足够的负担得起的营养安全食品的能力。该项目显然属于这一范围，因为它旨在为羊和牛的寄生虫控制提供循证建议，从而提高肉和奶的产量。通过更好地控制寄生虫，促进对明智使用驱虫药的战略指导，同时确定现场出现的耐药性，该项目将改善动物福利、羊和牛的饲料转化和营养，使肉类和牛奶生产更加高效、可持续和具有成本效益；对国民生产总值的直接贡献。该建议涉及农业和粮食安全中的若干优先领域，例如：动物健康、管理动物福利和加强可持续农业生产。该学生将获得与农民一起工作的经验，证明这项研究的高影响力，这也是BBSRC的目标。

Fasciola hepatica, the common liver fluke is a major cause of disease and production loss in sheep and cattle in the UK and changes in farming practices and climate are leading to increased prevalence and movement of infection into new areas of the UK. To control liver fluke we rely on repeated use of anthelmintic drugs (flukicides), particularly, triclabendazole, to which widespread drug-resistance is now reported. The concern is that as farmers turn to other drugs such as closantel, that resistance will now emerge to these drugs that are currently effective in the majority of cases. The aim of this project is to use in vitro methods to screen parasites displaying resistance to these alternative flukicides and genetically determine what genes are responsible so that we can better understand how parasites become resistant but also so we can detect and pre-empt the development of multi-drug resistance by providing best practice advice on anthelmntic use to farmers. In addition to developing high level genomic and bioinformatics skills, you will work directly with farmers. This project would be ideal for a qualified veterinary surgeon, or biology graduate with an interest in veterinary science, who wishes to develop skills in advanced next generation sequencing.BBSRC's Strategic Priorities include an emphasis on 'Agriculture and food security' and specifically: improving the UK's capacity to produce sufficient affordable nutritious safe food. This project falls clearly within that remit because it aims to provide evidence-based advice on parasite control in sheep and cattle and therefore improve meat and milk production. By achieving better control of parasites, promoting strategic guidance on judicious use of anthelmintics whilst identifying the emergence of drug resistance in the field, this project will improve animal welfare, feed conversion and nutrition of sheep and cattle, making meat and milk production more efficient, sustainable and cost-effective; contributing directly to national GDP. The proposal addresses several priority areas within agriculture and food security, such as: animal health, welfare of managed animals, and enhancing sustainable agricultural production. The student will gain experience in working with farmers, demonstrating the high impact of this research, also a target for BBSRC.