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ESR9 Understanding allosteric and biased GPCR signalling from computer simulations and mutagenesis

PhD project title

Understanding allosteric and biased GPCR signalling from computer simulations and mutagenesis  

Outline description, including interdisciplinary, intersectoral and international dimensions 

G protein-coupled receptors (GPCRs) are biological microprocessors that activate multiple signalling pathways in cells. Selective activation or inhibition of specific signalling pathways by small molecule ligands offer the potential for more targeted therapeutics with less side effects. Recent advances in structural determination of GPCRs conformations together with accumulated pharmacological studies of GPCR chemical modulators provide an exciting opportunity to explore receptor biased signalling at the atomic level. This project aims to provide the structural context of the ligand-determined receptor signalling pathways by studying the dynamic nature of ligand-receptor interactions in realistic environment and validating computer predictions through mutagenesis and functional assays. This project will aim to provide a groundwork for developing safer and more targeted pharmacological therapies. This interdisciplinary project is a collaborative effort bringing together the GPCR experience and expertise in molecular modelling from Dr. Tikhonova’s lab and pharmacology from Dr. Plouffe’s lab. Early Stage Researcher (ESR) will have the opportunity in training and learning of membrane simulations, molecular docking and cheminformatics tools in the Tikhonova lab; and mutagenesis, functional assays and compound screening in the Plouffee lab. In addition, the ESR will be involved in mathematical, physical and computing aspects of the project with physicists and engineers from the QUB Computational & Simulation Network (CoSiNe) and in chemical and biological aspects of the project with researchers from the School of Pharmacy, Pioneer Research Centre in Pharmaceutical Sciences (PRCPS) and Centre Experimental Medicine. The Tikhonova’s lab is a part of CoSiNe and PRCPS and benefit from interactions and facilities of both. The ESR will explore his/her knowledge in cheminformatics and conduct assessment of computational protocols for industrial drug discovery collaborating with an industrial partner.

Key words/descriptors



Molecular simulations, cheminformatics, drug design, allosteric ligand, biased signalling, mutagenesis, GPCRs

Fit to CITI-GENS theme(s)

  • Information Technology
  • Life Sciences

Supervisor Information



First Supervisor:          Dr. Irina Tikhonova                                               School: Pharmacy

Second Supervisor:    Dr. Bianca Plouffe                                                  School: Medicine, Dentistry and Biomedical Sciences

Third Supervisor:   Dr Stephen Garland                                                   Company: NQuiX

Name of non-HEI partner(s)

NQuiX at Stevenage Bioscience Catalyst


Contribution of non-HEI partner(s) to the project:



The ESR will have an opportunity of industrial supervision and guidance from Dr Stephen Garland at Stevenage Bioscience Catalyst. The main task of NQuiX is to engage the ESR in industrial computational drug design approaches. Placement at NQuiX will provide also interactions with the open innovative environment of the Stevenage Bioscience Catalyst Centre, where the ESR can meet other industrial drug discovery scientists.

Research centre / School

Pioneer Research Centre in Pharmaceutical Sciences, School of Pharmacy and Centre of Experimental Medicine. 

Subject area

Life Science