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. We are part of the Institute for the Physics of Living Systems (IPLS, https://www.ucl.ac.uk/physics-living-systems/), a lively cross-faculty institute with a mission to promote interdisciplinary research for a fundamental understanding of the complex behaviours of living systems.
Eligibility: Applicants must be UK nationals or have EU settled status or indefinite leave to remain under the EU Settlement Scheme. 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.
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 ([Email Address Removed]) 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.
Application deadline: February 18th 2021. Interviews to be held in February-March 2021. Only shortlisted candidates will be notified via email.
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