Demystifying the activation mechanism of Glucagon-Like Peptide-1 Receptor (GLP-1R)

Eligibility: UK/EU/International graduates with the required entry requirements

Funding details: Bursary plus tuition fees (UK/International (including EU at international rates from Sept 21)

Duration: Full-Time – between three and three and a half years fixed term

Application deadline: 27 May 2023

Interview date: Will be confirmed to shortlisted candidates

Start date: September 2023

For further details contact: Dr Giuseppe Deganutti

Project Details

The glucagon-like peptide receptor (GLP-1R) is a validated target for type 2 diabetes (T2D). The structure of GLP-1R and how new potential T2D oral drugs bind are well known. However, we have no information about the dynamic process leading to drug:receptor complex formation. 

The project aims to develop and apply state-of-the-art computational modelling via advanced molecular dynamic simulations to understand the complete binding mechanism of the human hormone GLP-1 and drug-like molecules recently discovered. This project is composed of two parallel and independent work strands. One line of research will focus on the endogenous agonists, i.e. GLP-1, while the other will address recently discovered non-peptidic agonists and their binding mechanism. This in-silico investigation will deliver, for the first time, a complete GLP-1R binding model, paving the way to the rational design of a new generation of medicines against T2D.

The project will advantage from collaborations with world-leading scientists from Monash University (AUS) and Imperial College (UK).

References

• Activation of the GLP-1 Receptor by a Non-Peptidic Agonist. Nature 2020, 577, 432–436
• Structure and Dynamics of the Active Gs-Coupled Human Secretin Receptor. Commun. 2020, 11, 4137.
• Structural and Functional Diversity among Agonist-Bound States of the GLP-1 Receptor. Chem. Biol. 2021, 18, 256–263
• Dynamics of GLP-1R Peptide Agonist Engagement Are Correlated with Kinetics of G Protein Activation.  Nature Commun. 2022, 13, 92

Funding

This is a fully-funded studentship, including tuition fees and a stipend/bursary. 

Benefits

The successful candidate will receive comprehensive research training including technical, personal and professional skills.

All researchers at Coventry University (from PhD to Professor) are part of the Doctoral College and Centre for Research Capability and Development, which provides support with high-quality training and career development activities. 

Entry Requirements

• A bachelor’s (honours) degree in a relevant discipline/subject area with a minimum classification of 2:1 and a minimum mark of 60% in the project element (or equivalent), or an equivalent award from an overseas institution.
  PLUS 
• The potential to engage in innovative research and to complete the PhD within 3.5 years.
• An adequate proficiency in English must be demonstrated by applicants whose first language is not English. The general requirement is a minimum overall IELTS Academic score of 7.0 with a minimum of 6.5 in each of the four sections, or the TOEFL iBT test with a minimum overall score of 95 with a minimum of 21 in each of the four sections.

Additional Requirements

• First degree or equivalent in chemistry, medicinal chemistry, biochemistry, cheminformatics, computational chemistry or a related discipline. A MSc would be desirable.
• Some background and/or strong interest for learning python or other programming languages
• Some background in computational chemistry, biomolecular simulations and/or adaptive molecular dynamics techniques (e.g. supervised molecular dynamics) would be desirable.