BBSRC White Rose DTP Studentship - Using AlphaFold structure predictions to accelerate molecular and genetic dissection of protein-protein interactions in intracellular polarity signalling

Cell signalling is a fundamental process in multicellular organisms that is required for the coordination of developmental and physiology. It often involves multi-protein complexes (e.g. ‘signalosomes’) that form via multivalent protein-protein interactions and phase transitions. Molecular, cellular and structural biology studies have been instrumental in understanding complex function for well-studied signalling pathways. However, many pathways remain to be explored and a major bottleneck is the difficulty of obtaining high quality structural information. The advent of the Alphafold AI-based structural prediction tool provides a potential shortcut for structure-function dissection of signalling pathways.

This interdisciplinary project will study planar polarity pathway protein complexes that assemble at cell junctions and transmit polarity signals between neighbouring cells. The composition and behaviour of these complexes is well-studied through cell biological and genetic studies, principally in Drosophila. Here we will attempt to understand the molecular basis for complex formation. Alphafold will be used to identify putative protein-protein interaction interfaces. The predictions will then be tested using biochemical and cell biological assays and further confirmed using cryoEM studies. Finally, the functional consequences of mutations will be tested in vivo in transgenic Drosophila.

The BBSRC WR DTP and the University of Sheffield are committed to recruiting future scientists regardless of age, ethnicity, gender, gender identity, disability, sexual orientation or career pathway to date. We understand that commitment and excellence can be shown in many ways and we have built our recruitment process to reflect this. We welcome applicants from all backgrounds, particularly those underrepresented in science, who have curiosity, creativity and a drive to learn new skills.

Note: Relocation costs for international students to the UK (visa, insurance, NHS fees, flights, etc) will be the responsibility of the student 

Entry Requirements: Students with, or expecting to gain, at least an upper second class honours degree, or equivalent, are invited to apply. The interdisciplinary nature of this programme means that we welcome applications from students with backgrounds in any biological, chemical, and/or physical science, or students with mathematical backgrounds who are interested in using their skills in addressing biological questions. 

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Programme: PhD in Mechanistic Biology (4 years)

Start Date: 1st October 2023

Shortlisted candidates will be interviewed mid February 2023