Combining molecular biology and computer modelling to enhance control of liver fluke in livestock across agricultural landscapes

肝片吸虫是一种高致病性吸虫寄生虫，在全球牛和羊中高度流行，其疾病和肝片吸虫病每年给欧洲畜牧业造成超过20亿GB的损失。气候变化和驱虫药耐药性正在推动全球肝吸虫流行率的上升。这种发病率的增加严重影响了动物的健康、福利和生产力，并威胁到某些地区畜牧业生产的可持续性。为了减轻这种威胁，并在未来几十年可持续地控制肝吸虫，需要替代的非化学控制策略。这些替代策略可能针对肝片吸虫的生命周期，它围绕着一个中间钉螺宿主(Galba Truncatula)。这种蜗牛只存在于最佳环境和小气候条件允许其繁衍生息的牧场地区。包括放牧轮换、对风险地区进行临时或永久围栏以及有针对性地处理牲畜以减少牧场污染肝片吸虫卵的战略可能会阻碍其生命周期。然而，主要障碍阻碍了这些替代控制策略的大规模采用。对农场中的元胞原虫栖息地的空间分布缺乏了解，这阻碍了农民成功地采用针对钉螺的措施的能力。关于如何以最佳方式应用这些替代策略的信息也有限，包括它们应该在一年中的哪些时段使用以及使用多长时间。近年来，该项目的监督团队开发了新的研究工具，使研究人员能够在现场水平上调查元胞原虫和肝片吸虫的流行病学。这些措施包括开发可识别农田中是否存在元胞原虫的环境DNA分析方法(Jones等人，2018年)，以及可随时间推移在农场一级准确模拟肝片吸虫感染风险的机械建模技术(Beltrame等人，2018年)。这个项目的目的是利用这些工具来开发和评估农场特定的指导，以成功地应用非化学控制方法在英国农场控制肝片吸虫。在博士课程中，未来的学生将评估和比较一系列DNA提取方法和分子工具，以确定捕获、提取和扩增元胞杆菌的最佳方法。然后，确定的最优方法将被应用于调查英国多个农场的元宵草栖息地。还将在这些采样点收集环境和气候测量数据，并结合EDNA调查结果进行分析，以确定与农田水分饱和生境中的元胞螺有关的因素。最后，机械模型将评估放牧轮换、对元胞原虫栖息地的临时和永久围栏以及为将牧场吸虫卵污染降至最低而进行的针对性治疗对通过EDNA调查研究和绘制的农场放牧牲畜未来感染肝片吸虫的风险的影响。这些模型还将评估应用这些策略的最佳时间框架，天气如何与农场地形和结构相互作用来影响它们的成功，以及如何改变牧场结构以增强基于放牧的控制对吸虫和混合感染线虫寄生虫的影响。未来的学生将获得分子生物学、寄生虫学、计算建模、通用研究方法和通信方面的跨学科技能。具体地说，未来的学生将发展执行一系列DNA提取和扩增方法的技能，从形态上识别蜗牛的中间宿主和寄生虫的生活阶段，并开发和应用机械模型。培训将由监督小组和Aberystwyth大学研究生院博士培训方案提供。

Liver fluke (Fasciola hepatica) is a highly pathogenic trematode parasite that is highly prevalent in cattle and sheep globally, with its disease, fasciolosis estimated to cost European livestock producers over £2 billion annually. Climate change and anthelmintic resistance are driving increasing liver fluke prevalence globally. This increase in prevalence is seriously impacting animal health, welfare and productivity, and threatening the sustainability of livestock production in certain regions.To alleviate this threat, and to sustainably manage liver fluke in future decades, alternative non-chemical control strategies are required. These alternative strategies may target the F. hepatica lifecycle, which revolves around an intermediate snail host (Galba truncatula). This snail is only present in areas on pastureland where optimal environmental and microclimatic conditions allow it to thrive. Strategies including grazing rotation, temporary or permanent fencing of risk areas and targeted treatment of livestock to reduce pasture contamination of F. hepatica eggs can impede the lifecycle. However, major barriers prevent the mass adoption of these alternative control strategies. Poor understanding of the spatial distribution G. truncatula habitats on farms impedes on the ability of farmers to successfully apply measures targeting the snail. There is also limited information regarding how these alternative strategies can be optimally applied, including which periods of the year they should be employed and for how long.In recent years, the project's supervisory team have developed novel research tools that allow researchers to investigate the epidemiology of G. truncatula and F. hepatica at field level. These include the development of environmental DNA assays which can identify the presence of G. truncatula on farmland (Jones et al., 2018), and mechanistic modelling techniques which can accurately model F. hepatica infection risk over time at farm level (Beltrame et al., 2018). This project aims to utilise these tools to develop and evaluate farm specific guidance for successful application of non-chemical control methods for F. hepatica control on UK farms.During the PhD programme, the prospective student will evaluate and compare a range of DNA extraction methods and molecular tools to identify optimal methodology for G. truncatula eDNA capture, extraction and amplification. The optimal methodologies identified will then be applied to survey G. truncatula habitats on multiple UK farms. Environmental and climatic measurements will also be gathered in these sampling sites and analysed in conjunction with eDNA survey results to identify factors associated with the presence of G. truncatula snails in water-saturated habitats on farmland. Finally, mechanistic models will evaluate the impact of grazing rotations, temporary and permanent fencing of G. truncatula habitats and targeted treatment to minimise pasture contamination of fluke eggs on future F. hepatica infection risk in grazing livestock on farms studied and mapped via eDNA survey. These models will also evaluate the optimal timeframe for the application of these strategies, how weather interacts with farm topography and structure to affect their success, and how pasture architecture can be altered to enhance impact of grazing-based control, for fluke and co-infecting nematode parasites.The prospective student will acquire inter-disciplinary skills in molecular biology, parasitology, computational modelling and generic research methods and communication. Specifically, the prospective student will develop skills to perform a range of DNA extraction and amplification methodologies, to morphologically identify intermediate snail host and parasite life stages and to develop and apply mechanistic models. Training will be provided by the supervisory team and by Aberystwyth University's Graduate School Doctoral Training Programme.