PhD Studentship: Molecular Engineering of Protein-Lipid Interactions for Immunotherapy

About the Project

Funding availability: These studentships are normally only available to home (UK) students, but there are a limited number of studentships available to overseas students.

Start date: October 2024

Duration: 3.5 years

Deadline: Applications will be considered on a rolling basis until the post is filled. Final deadline 1st April 2024.

Project Description:

Biological membranes display exquisite organisation, in part through the formation of highly ordered lipid microdomains (or “lipid rafts”). Lipid microdomains are formed by lipid-lipid phase separation, leading to patches of membrane enriched in saturated lipids, cholesterol, glycolipids, and sphingolipids. These regions have been shown to facilitate spatial separation of proteins, and microdomain association correlates strongly with cell signalling in many biological contexts - offering a route for molecular pre-organisation in a synthetic cell.

The challenge for designing synthetic mimics of lipid microdomains is that lipid-lipid phase separation and the preferential interactions that drive protein recruitment to these domains are not well understood. We aim to take a molecular engineering approach to (i) create lipid microdomains and (ii) use these domains to drive pre-assembly of a transmembrane protein complex. We will build in complexity from the bottom-up, and this work could ultimately lead to new cell-based immunotherapies to fight diseases such as cancer.

We are currently advertising a PhD position in this area (funded by an EPSRC DTP Studentship) in the Dept. of Chemistry at Warwick co-supervised by Dr Ann Dixon and Dr Becky Notman. In this project, we will explore microdomain formation in synthetic immune cells using biophysical techniques including fluorescence spectroscopy/microscopy, SAXS, ITC, cryo-EM and in in silico model membranes using coarse-grained molecular dynamics computer simulations.  We will also explore the partitioning of proteins into lipid microdomains, evaluating the impact of lipid type and protein sequence using a wide range of biochemical and biophysical methods including circular dichroism and NMR spectroscopy. This work will provide a deeper understanding of the “communication” between proteins and membranes that we will use to design a synthetic cell, e.g. a synthetic immune cell.

This is an exciting opportunity for a student with a background in physical sciences to develop their expertise in both biophysical chemistry and computational chemistry. There are a huge number of possible applications of the work, so it will be a great time to get involved and publish in a new area of chemistry from the early stages. 

Requirements:

Applicants should have a good degree (at least II.1 or equivalent) in chemistry, physics, natural sciences, or other relevant discipline.

How to apply:

Informal enquiries to either supervisor are welcomed (please include a CV). Please email Dr Ann Dixon ([email protected] ) or Dr Becky Notman ([email protected] ).

Details on the formal application procedure can be found via the 'Apply' button.

Applications will be considered on a rolling basis until the post is filled.

Funding Notes

Funding availability: 3.5 years funding by an EPSRC DTP studentship.

The studentship will begin in October 2024 and will provide funding for tuition fees and a maintenance grant at the standard UKRI rate.