PhD in Pharmacological Inhibitors of Cancer-Associated Adhesion GPCR in Zebrafish Embryo (MRC DiMeN DTP)

This fully funded PhD project at the University of Sheffield, as part of the MRC Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), focuses on the search for pharmacological inhibitors of the cancer-associated adhesion GPCR, ADGRG6 (GPR126), using the zebrafish embryo as a model system. ADGRG6 is an adhesion class G-protein-coupled receptor of significant clinical interest, with recessive mutations causing rare congenital neurological diseases and altered activity linked to increased cancer risk and poor prognosis in adults. The project aims to identify and test small-molecule inhibitors of the ADGRG6 pathway, which could serve as potential therapeutic anti-cancer agents. The student will conduct unbiased compound screens and candidate compound treatments in zebrafish embryos, followed by dose-response assays and analysis of mRNA or protein markers. The research will involve examining tissues where adgrg6 is expressed, such as the developing ear, nose, and Schwann cells, and will utilize chemoinformatic approaches to optimize pharmacological properties of promising compounds. There is also an opportunity to investigate tumor risk in new adgrg6 genetic variants. The project is highly interdisciplinary, combining wet lab techniques (zebrafish handling, fluorescent in situ hybridization, immunohistochemistry, confocal and light-sheet microscopy) with computational methods (bioinformatics, chemoinformatics, image analysis). The student will join the Whitfield lab, a well-funded and supportive research group, and benefit from an interdisciplinary supervisory team and an established advisory program. The DiMeN DTP offers a vibrant community, bespoke training, and access to state-of-the-art facilities across partner institutions. Funding covers tuition, stipend (£20,780 for 2024/25), and project costs for 4 years, with limited awards for exceptional international applicants. Applicants should have a strong background in a relevant subject, and non-native English speakers must meet language requirements. Applications are submitted via the DiMeN website, and further details are available online.