Is it a Fluke or is it Reproducible: Understanding Isolate Variation in Fasciola hepatica for Diagnostic Potential

是侥幸还是可重复：了解肝片吸虫的分离株变异以实现诊断潜力

• 批准号: 2749697
• 金额: --
• 依托单位: Aberystwyth University
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2749697
• 关键词: Fluke; Reproducible; Understanding; Isolate; Variation

Helminth parasites are responsible for >55% of livestock diseases representing a major threat to global food security and food borne disease, with control being through anthelmintic drugs due to an absence of vaccines. In particular, zoonotic fascioliasis, caused by liver fluke, has a profound, negative impact on livestock production and welfare, causing death or chronic wasting disease and predisposition to bacterial diseases with losses of ~$US3 billion/annum worldwide. With a reliance on triclabendazole (TCBZ) as the frontline anthelmintic drug, control has been hampered by the emergence of TCBZ resistance. To facilitate improved control, there is now an urgent need for new diagnostics capable of differentiating between liver fluke that are TCBZ resistant and those that are TCBZ susceptible. New liver fluke isolates, that are both susceptible and resistant to TCBZ, are now available to explore using post genomic technologies to generate the next generation of liver fluke diagnostics. Therefore, this project aims to employ a multiomic approach to reveal liver fluke isolate specific profiles that can be exploited for TCBZ differentiation diagnostics and to support the confirmation of isolate TCBZ status. This project will aim to 1) Utilise proteomics to fingerprint liver fluke isolate somatic1, excretory-secretory and extracellular vesicle2 proteins 2) Transcriptome profile liver fluke isolates for sequence variations 3) Optimize Liquid AP (MA)LDI to Support Rapid Isolate Differentiation and 4) develop a pilot pen-side diagnostic test. This work will importantly lay the foundations to support future TCBZ resistance/susceptibility diagnostics for the liver fluke.The student will gain experience and training in a wide range of molecular and parasitological methods including biochemistry, molecular biology and in vitro parasite maintenance. This will also include purification and analysis of extracellular vesicles. In addition, training will be provided in multiomics technologies and bioinformatics for the analysis of large-scale omic datasets. Furthermore, the student will gain experience in analytical mass spectrometry and biomolecule purification. The student will also spend time with Ridgeway Research Ltd, a UK-based veterinary service firm, where they will receive training in parasite life cycle management. The student will also play a central role in communicating project goals and progress with stakeholders (local farmers and farmers unions etc).

蠕虫寄生虫造成了>55%的牲畜疾病，这对全球粮食安全和食源性疾病构成了重大威胁，由于缺乏疫苗，控制是通过驱虫药物进行的。特别是，由肝吸虫引起的人畜共患片形吸虫病对牲畜生产和福利具有深远的负面影响，导致死亡或慢性消耗性疾病和易患细菌性疾病，全世界每年损失约30亿美元。由于依赖三氯苯达唑（TCBZ）作为一线驱虫药，TCBZ耐药性的出现阻碍了控制。为了促进改进控制，现在迫切需要能够区分TCBZ耐药肝吸虫和TCBZ敏感肝吸虫的新诊断方法。对TCBZ既敏感又耐药的新肝吸虫分离株现在可用于探索使用后基因组技术来产生下一代肝吸虫诊断。因此，本项目旨在采用多组学方法来揭示肝吸虫分离株的特异性谱，这些谱可用于TCBZ分化诊断，并支持分离株TCBZ状态的确认。该项目的目标是：1）利用蛋白质组学对肝吸虫分离株体细胞1、排泄分泌和细胞外囊泡2蛋白进行指纹分析; 2）肝吸虫分离株的转录组谱序列变异; 3）优化液体AP（MA）LDI以支持快速分离株分化; 4）开发一种试验性笔旁诊断测试。这项工作将为肝吸虫TCBZ耐药/敏感性诊断奠定基础。学生将获得广泛的分子和寄生虫学方法的经验和培训，包括生物化学，分子生物学和体外寄生虫维持。这也将包括细胞外囊泡的纯化和分析。此外，还将提供多组学技术和生物信息学方面的培训，以分析大规模组学数据集。此外，学生将获得分析质谱和生物分子纯化的经验。学生还将花时间与里奇韦研究有限公司，一家英国兽医服务公司，在那里他们将接受寄生虫生命周期管理的培训。学生还将在与利益相关者（当地农民和农民联盟等）沟通项目目标和进展方面发挥核心作用。