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Spatio-temporal information in receptor signalling in health and diseases


School of Mathematics

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Dr F Spill , Prof M Canals No more applications being accepted Competition Funded PhD Project (Students Worldwide)
Birmingham United Kingdom Mathematical Modelling

About the Project

GPCR activated signalling pathways regulate virtually all cell functions, including cell proliferation, death or migration. These pathways are therefore associated with a wide range of diseases, including neuropsychiatric diseases and pain. Indeed, 30% of all FDA approved drugs target a GPCR. Despite the importance of these pathways, most of our understanding is based on experimental techniques and simple mathematical models that describe receptor activation and the initiation of downstream signalling that lack predictive power. Recent research revealed a complex spatio-temporal organisation of the ligands, drugs and downstream molecules that regulate the cell functions, highlighting the need of updated models to predict the actions of these receptors.

In this project, the successful applicant will develop a new understanding of drug action on receptor activation by uncovering the spatio-temporal organisation of two typical GPCRs, the dopamine and the opioid receptors. Through imaging and biophysical approaches, we will uncover how different drugs induce differential downstream signals, facilitated by different G-proteins, beta-arrestins and other intracellular effectors. A new mathematical model of receptor activation will predict these differential responses. These predictions will be tested experimentally and will therefore allow the identification of more effective drugs to target the different diseases activated by these model GPCRs.

Person Specification

Applicants should have a strong background in either mathematical, computational or experimental biology, or closely related fields. They should have a commitment to interdisciplinary research and hold or realistically expect to obtain at least an Upper Second Class Honours Degree in mathematics, physics, computer science, biology or related subjects. It is not required to be familiar with both mathematical and experimental approaches, and the student may choose to specialize in one or the other. However, willingness to work in an interdisciplinary environment and collaborate with experts in other fields is essential. The successful applicant will be supported by training on all required methods, and benefit from a unique interdisciplinary experience that is highly considered in academia and industry.

Applications to be made via the MRC IMPACT website


Funding Notes

Full details on eligibility, including residence requirements can be found on the UKRI website and on the MRC IMPACT website https://more.bham.ac.uk/mrc-impact/phd-opportunities/
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