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BBSRC White Rose DTP Studentship - Uncovering ligand-receptor interactions in the zebrafish model

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  • Full or part time
    Prof T T Whitfield
    Dr A de la Vega de Leon
    Dr S Baxendale
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Understanding how small molecules affect the activity of signalling pathways underpins the discovery of molecular tools for pathway manipulation and the design of new therapeutic compounds. This project focusses on the adhesion class G protein-coupled receptor Adgrg6 (Gpr126), which has an important role in morphogenesis of the developing inner ear. Our recent work has identified classes of small molecules that can rescue both morphogenetic and gene expression defects in the ears of zebrafish adgrg6 mutants (Diamantopoulou et al., eLife, 2019). We have evidence to suggest that some of these compounds interact with the Adgrg6 receptor directly.

The aim of this PhD project is to understand the mechanism of action of selected hit compounds: how putative ligands interact with the receptor, and how their action alters pathway activity and downstream gene expression in the developing ear. The successful student will tackle these questions in silico and in vivo. Computational chemoinformatic approaches will be used to understand structure-activity relationships of different compound classes. CRISPR/Cas9 gene editing will be used to test the action of candidate target genes and their function in the developing inner ear, using the zebrafish embryo as a model system.

This exciting interdisciplinary project combines developmental biology, chemoinformatics, and molecular and genetic approaches. The student will gain experience in working with zebrafish embryos, and in the use of data-driven computational techniques. There will be ample opportunity to contribute to experimental design and to gain experience in presentation, teaching and outreach.

The student will join the White Rose Doctoral Training Programme, which offers an attractive package of student training and cohort activities. The 4-year funding includes a generous training allowance that can support attendance at scientific meetings. The studentship will include a 3-month placement at a company or organisation of the student’s choice.

Informal enquiries: Please contact Professor Tanya Whitfield ([Email Address Removed])

Funding Notes

- a tax-free stipend at the standard Research Council rate (~£15,009, to be confirmed for 2020) for 4 years
- tuition fees at the UK/EU rate for 4 years.
- research costs

At least a 2:1 honours degree in a relevant subject or equivalent. The interdisciplinary nature of this programme means that we welcome applications from students with backgrounds in any biological, chemical, and/or physical science, students with mathematical backgrounds who are interested in using their skills in addressing biological questions.

Studentships are available to UK and EU students who meet the UK residency requirements. Further information on eligibility: https://www.whiterose-mechanisticbiology-dtp.ac.uk/about-dtp/how-to-apply/.

References

Diamantopoulou E, Baxendale S, de la Vega de León A, Asad A, Holdsworth CJ, Abbas L, Gillet VJ, Wiggin GR, Whitfield TT (2019). Identification of compounds that rescue otic and myelination defects in the zebrafish adgrg6 (gpr126) mutant. Elife 8, e44889. doi: 10.7554/eLife.44889.

How good is research at University of Sheffield in Biological Sciences?

FTE Category A staff submitted: 44.90

Research output data provided by the Research Excellence Framework (REF)

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