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

肝片吸虫是一种全球性人畜共患吸虫病的病原学吸虫，在全球范围内影响着农业、兽医和医疗系统。主要杀虫剂三氯苯达唑(TCBZ)的广泛使用导致了驱虫药耐药性的产生，威胁到农业系统的安全和可持续性。肝片吸虫病现在被认为是一种新出现的被忽视的疾病，必须紧急优先研究新的治疗方法。组蛋白修饰酶(HMES)以前一直是驱虫发育研究的靶点，因为对曼氏血吸虫的研究已经证明这些酶对寄生虫的生长和发育具有靶向性影响。该项目旨在重新定位HME抑制剂，以确定它们作为新型杀线虫药物的潜力。为了实现这一目标，主要有三个目标：1)肝片吸虫组蛋白修饰酶的特性。2)确认HME是潜在的抑制剂靶标。3)改进图像分析工具和AI模型，用于幼年阶段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.