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School of Physical and Chemical Sciences

Molecular Modelling of an orphan G-protein coupled receptor with cardiovascular function

Research Group: Chemistry
Number of Students: 1
Length of Study in Years: 4 Years
Full-time Project: yes

Funding

This studentship is funded via a studentship from the China Scholarship Council.  CSC is offering a monthly stipend to cover living expenses and QMUL is waving fees and hosting the student. These scholarships are available only for Chinese candidates. 

Project Description

G-protein coupled receptors (GPCRs) are transmembrane proteins involved in a wide range of cell signalling processes. Their regulation through small molecule modulators is used for the treatment of different types of diseases and GPCRs currently account for more than 30% of drug targets.

This project is part of a research collaboration led by the William Harvey Research Institute and focusing on an orphan receptor that has been recently shown to have a role in cardiovascular function. However, the development of small-molecule drugs that can regulate its activity is hindered by the absence of direct information on endogenous or exogenous ligands of the receptor.

The aim of this project is to use computational techniques to a) provide high quality models of the  structure and dynamics of the receptor, b) gain new insight into its mechanism of regulation and c) identify candidate ligands that can be subsequently tested with wet lab assays at WHRI. Available experimental information on this and other closely related receptors will be used to guide the modelling, the identification of druggable binding sites and the generation of libraries for the screening.

Research environment:

Dr Fornili’s research group focuses on the computational study of biomolecular dynamics and in particular of proteins involved in muscle contraction. Recent contributions from the lab include the study of the effects of a heart failure drug on cardiac myosin dynamics (J. Mol. Inf. Model., 2020; PLOS Comp. Biol., 2017), the first theoretical observation of a binding pocket induced by mechanical stress (JCTC, 2019) and the development of methods for the prediction of rescue binding pockets in proteins (Bioinformatics, 2018). The lab has regular access to national supercomputing facilities and is equipped with dedicated servers for biomolecular simulation and data storage. More information can be found at https://afornililab.wordpress.com.

The project is part of a wider collaboration led by Prof. Andrew Tinker at the William Harvey Research Institute and involving different research teams (Andrew Tinker, Peter McCormick and Patricia Munroe’s labs) with an outstanding track record of research on cardiovascular function and disease.

Techniques and Training: the successful candidate will be trained in different modelling techniques, including molecular docking, homology modelling, virtual screening, pharmacophore modelling and molecular dynamics simulations. The student will also use machine learning techniques for data analysis and learn how to implement structural analysis tools using scientific programming languages (R/Python).

 

 

Requirements

Supervisor Contact Details:

For informal enquiries about this position, please contact Arianna Fornili

E-mail: a.fornili@qmul.ac.uk

Application Method:

To apply for this studentship and for entry on to the Chemistry programme (Full Time) please follow the instructions detailed on the following webpage:

https://www.qmul.ac.uk/postgraduate/research/subjects/chemistry.html

Application Deadline - 31st of January 2023

 

SPCS Academics: Dr Arianna Fornili