Davide Calebiro

[Funded by BBSRC through the Midlands Integrated Biosciences Training Partnership; includes stipend and tuition fees.] This PhD studentship at the University of Birmingham, funded by the BBSRC through the Midlands Integrated Biosciences Training Partnership (MIBTP), focuses on the development of organelle-targeted ligands to delineate G protein-coupled receptor (GPCR) signalling. GPCRs are a large family of membrane proteins that play crucial roles in cell growth, neurotransmission, metabolism, and immune response, and are significant drug targets. While much is known about GPCR signalling at the cell surface, recent advances have shown that GPCRs can also signal from intracellular compartments, such as early endosomes and the Golgi apparatus, leading to distinct cellular effects. This project aims to develop and utilize advanced chemical biology tools and optical methods to control and monitor GPCR signalling with spatial and temporal precision, specifically focusing on the functional consequences of intracellular GPCR signalling. The research will leverage the expertise and facilities of the Centre of Membrane Proteins and Receptors (COMPARE) at Birmingham, and will use FFA44 and NTSR1 as model GPCRs. The student will design and synthesize small-molecule agonists and antagonists equipped with organelle localization sequences, light/enzyme-responsive uncaging groups, photoswitchable groups, and covalent warheads for conjugation to organelle-specific protein fusions. These tools will enable precise manipulation of GPCR activity within specific organelles, allowing the separation of intracellular from cell surface signalling and potentially paving the way for more selective and better-tolerated drugs. The successful candidate will join a vibrant, multidisciplinary research group and gain skills in synthetic chemistry, structural molecular biology, advanced imaging, and computational image analysis. The project is part of a collaborative partnership with several UK universities, offering a rich training environment. Funding covers tuition and a stipend. Applicants should have a strong background in a relevant discipline and an interest in chemical biology and advanced imaging. The application deadline is 27 November 2025.