PhD Studentship to investigate the mechanisms of cell-surface receptor clustering in virus entry

Updated: 10 days ago
Location: London, ENGLAND
Deadline: 18 Feb 2021

UCL Department / Division
UCL Physics and Astronomy
Location of position
London
Duration of Studentship
3.5 years
Stipend
£17,630 per annum
Vacancy Information
A 3.5-year PhD position is available from 1 student to work under the supervision of Prof. I. Llorente-Garcia.
Studentship Description
This PhD project will focus on developing novel simulations of receptor clustering in cell membranes. To infect a cell, viruses must penetrate cellular membrane barriers. Viruses engage specific receptors that typically cluster on the cell-surface upon virus binding, facilitating the molecular interactions that lead to penetration. Receptor clustering is known to influence the entry of viruses into cells, and so this research will have broad applicability to virus infection.
This project will require the student to develop numerical simulations using Python. These simulations will seek to elucidate the mechanisms by which receptor proteins redistribute and cluster in the plasma membrane of living host cells following virus-binding events. We will also aim at deciphering if and how specific cell-surface virus receptor molecules promote virus entry via receptor clustering.  This project will investigate how virus-induced recruitment of receptors takes place in time and space by considering: receptor diffusion in the membrane in the presence of thermal Brownian fluctuations, multi-valent binding of receptor proteins and virus-surface proteins, the effect of the cytoskeleton that underlies the cellular membrane (obstacles to diffusion and corralling of molecules), receptor dimerisation, the presence of inhomogeneous membrane domains (lipid rafts), membrane topography, etc. We will aim to find out the different time scales and typical numbers of receptor molecules per cluster for the different possible clustering mechanisms. 
Monte-Carlo simulations will be used to model these dynamic and stochastic systems. The main focus will be the Human Immunodeficiency Virus (HIV), for which specific receptors – the cell-surface proteins CD4 and CCR5/CXCR4 – are well characterised. These simulations will be used to understand experimental observations of clustering of the CD4 receptor acquired by our collaborators. We will use known CD4 parameters measured in experiments as inputs to the models. We also study the literature for other viruses to identify general mechanisms of receptor clustering in receptor-mediated virus entry.
You will work in an exciting multi-disciplinary environment under the supervision of Prof. I. Llorente-Garcia (https://illglab.wordpress.com/ ) in the Dept. of Physics and Astronomy at UCL. 
References:
A biophysical perspective on receptor-mediated virus entry with a focus on HIV, I. Llorente-Garcia and M. Marsh, BBA - Biomembranes 1862, 183158 (2020).
Mathematical Simulation of Membrane Protein Clustering for Efficient Signal Transduction, K. Radhakrishnan, A. Halasz, M. M. McCabe, J. S. Edwards and B. S. Wilson. Annals of Biomedical Engineering, 40, 2307–2318 (2012). 
Person Specification
A high grade point average (expecting to achieve a 1st or 2.1) MSci or Master’s degree (or equivalent) in Physics, Maths, Engineering or similar is required. No prior knowledge of Biology is necessary. Previous experience in computational projects and good programming skills in Python are highly desirable, along with an interest in biological physics. A high level of self-motivation and enthusiasm is essential, as well as good communication skills. Excellent writing skills are essential.
Eligibility
Please refer to the following website for eligibility criteria: https://www.ucl.ac.uk/physics-astronomy/study/phd
The start date is October 2021 (or sooner). The studentship will cover all university fees and includes funds for maintenance at the standard UK rate and for participation in international conferences and workshops. Due to funding restrictions, this studentship is open only to candidates who satisfy EPSRC eligibility requirements (i.e. from the UK/EU with 3 years residency in the UK). This funding is for UK/EU nationals candidates. Applicants must be UK nationals or have EU settled status or indefinite leave to remain under the EU Settlement Scheme . 
If you have any queries about this studentship, please contact  Prof. I. Llorente-Garcia,  i.llorente-garcia@ucl.ac.uk .
How to apply: Please follow the procedure outlined under “Application Procedure” at: www.ucl.ac.uk/physics-astronomy/study/phd , mention of the AMOPP group and notify the supervisor (i.llorente-garcia@ucl.ac.uk ) of your application. Electronic applications are therefore via https://www.ucl.ac.uk/prospective-students/graduate/apply . You will need a CV, an electronic copy of your academic transcript, contact details for two references and a personal statement. Outline in your statement (750 words maximum) your academic excellence, research experience to date and suitability for the project. 
Please include a contact telephone number and an email address where you can be easily reached. References will be taken up for all short-listed candidates. Only shortlisted candidates will be contacted. 
Contact name
Isabel Llorente-Garcia
Contact details
i.llorente-garcia@ucl.ac.uk
UCL Taking Action for Equality
Closing Date
18 Feb 2021
Latest time for the submission of applications
23:59
Interview date
tbc
Studentship Start Date
October 2021
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