Repositioning histone modifying enzyme (HME) inhibitors as next-generation flukicides

肝片形吸虫是全球性人畜共患病肝片形吸虫病的病原之一，在全球范围内影响农业、兽医和医疗系统。主要杀吸虫剂三氯苯达唑（TCBZ）的广泛使用已导致驱虫剂产生抗药性，威胁到农业系统的安全性和可持续性。肝片吸虫病现在被认为是一种新兴的被忽视的疾病，必须紧急优先研究新疗法。组蛋白修饰酶（HME）此前曾是驱虫药开发研究的目标，因为对曼氏血吸虫的研究已证明这些酶对寄生虫生长和发育具有靶向影响。该项目旨在重新定位HME抑制剂，以确定其作为新型杀吸虫剂的潜力。为了实现这一点，有三个主要目标：1）肝片吸虫的组蛋白修饰酶的表征。2)验证HME作为哺乳动物的潜在靶标。3）改进图像分析工具和AI模型，用于幼年期的运动性和表型评分。

Fasciola hepatica is one of the aetiological trematodes of the global zoonotic disease, fascioliasis, which impacts agricultural, veterinary and medical systems on a global scale. Widespread use of the primary flukicide, triclabendazole (TCBZ) has led to developing anthelmintic resistance which threatens the security and sustainability of agricultural systems. Fascioliasis is now considered an emerging neglected disease and research efforts into novel therapies must urgently be prioritised. Histone modification enzymes (HMEs) have previously been targeted in anthelmintic development research, as studies in Schistosoma mansoni have demonstrated a targetable influence of these enzymes over parasite growth and development. This project aims to reposition HME inhibitors to determine their potential as novel flukicides. To achieve this, there are three main objectives:1) Characterisation of the histone modification enzymes of Fasciola hepatica. 2) Validation of HMEs as potential targets for inhibitors.3) Improvement of image analysis tools and AI models for motility and phenotype scoring in the juvenile stage.