PhD Studentship: Demystifying the Activation Mechanism of Glucagon-Like Peptide Receptor 1

Coventry University (CU) is inviting applications from suitably-qualified graduates for a fully-funded PhD studentship.

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). 

Bibliography 

• 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. Nat. Commun. 2020, 11, 4137.
• Structural and Functional Diversity among Agonist-Bound States of the GLP-1 Receptor. Nat. Chem. Biol. 2021, 18, 256–263
• Dynamics of GLP-1R Peptide Agonist Engagement Are Correlated with Kinetics of G Protein Activation. Nat. Commun. 2022, 13, 92

Entry criteria for applicants to PhD  

• 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.

For further details please visit:  https://www.coventry.ac.uk/research/research-opportunities/research-students/making-an-application/research-entry-criteria/ 

https://www.coventry.ac.uk/research/research-opportunities/research-students/making-an-application/ 

To find out more about the project please contact Dr Giuseppe Deganutti (ad5288@coventry.ac.uk)

To apply on line please visit: Home Page | PGR+ Application (coventry.ac.uk) 

The PGR+ Link for this project is 

Details of all available research opportunities at Coventry University can be found via

https://www.coventry.ac.uk/research/research-opportunities/

All applications require full supporting documentation, and a covering letter – plus one of the following (please select one option)

For pre-determined (named) projects an up-to 2000-word supporting statement is required showing how the applicant’s expertise and interests are relevant to the project. 

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