Building confidence in non-protected zebrafish embryo-larvae as a viable alternative to mammalian DART assessment. (Ref 4649)

建立对非受保护斑马鱼胚胎幼虫作为哺乳动物 DART 评估的可行替代方案的信心。

• 批准号: 2867639
• 金额: --
• 依托单位: UNIVERSITY OF EXETER
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2867639
• 关键词: Building; confidence; non; protected; zebrafish

Developmental and Reproductive Toxicity (DART) tests are conducted in rodent and rabbit models in order to assess for chemical risk to human health. There is an urgent need to refine the processes used to assess DART endpoints using alternative tests. This need has been recognised by the DART research community, regulators, and pharmaceutical and agrochemical industries. Recently the use of so called 'New Approach Methodologies' (NAMs) for alternative assessments have been proposed. NAMs, which include the zebrafish, have the potential to significantly reduce the numbers of mammals used in DART assessment by the pharmaceutical industry and supporting the principle of replace, reduce, refine (3Rs) in testing.The student will join a large vibrant research team in Biosciences at Exeter and recieve training in cutting edge molecular technologies, bioinformatics, in-life studies, advanced imaging techniques and pathology, as applied to developing non-mammalian alternative models and driving the NC3Rs principles in animal use. Working in collaboration and alongside our industry partner, AstraZeneca (both in the UK and Sweden) the project will include use a novel gene editing technology (CRISPR/Cas9) to generate a new zebrafish model for assessing teratogenic effects of pharmaceuticals. The student will work also with NC3Rs, and engage with academics and stakeholders more widely to help illustrate the utility of zebrafish in non-protected life stages (up to 4dpf) for detecting developmental effects of selected ImmunoModulatory imide drugs known to induce teratogenic effects in humans/rabbits (e.g., thalidomide, lenalidomide and pomalidomide).

为了评估人类健康的化学风险，在啮齿动物和兔子模型中进行了发育和生殖毒性（DART）测试。迫切需要使用替代测试来完善用于评估飞镖端点的过程。这项需求已被DART研究界，监管机构以及药物和农业化学行业所认识到。最近，已经提出了所谓的“新方法方法”（NAM）进行替代评估。包括斑马鱼在内的NAM有可能显着减少制药行业中DART评估中使用的哺乳动物数量，并支持替换，减少，完善，预先提炼（3R）的原则。学生将加入一个大型充满活力的研究团队在埃克塞特（Exeter）的生物科学中，并在尖端分子技术，生物信息学，生活研究，高级成像技术和病理学中获得了培训，适用于开发非哺乳动物替代模型并推动动物使用中的NC3RS原理。该项目在合作和行业合作伙伴Astrazeneca（包括在英国和瑞典）一起工作，包括使用新型的基因编辑技术（CRISPR/CAS9）来生成一种新的斑马鱼模型来评估药物的致病作用。该学生还将与NC3RS合作，并与学者和利益相关者进行更广泛的互动，以帮助说明斑马鱼在未受保护的生命阶段的实用性（最高4DPF），以检测所选免疫调节性Imide药物的发育效果/兔子（例如沙利度胺，勒纳略胺和果皮胺）。