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

点击翻译按钮获取中文摘要

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).