A new platform to understand and control protein liquid-liquid phase separation

This project is sponsored by the Institute of Chemical Biology EPSRC Centre for Doctoral Training

Supervisors:

Dr Francesco Aprile (Department of Chemistry, ICL)

Professor Ramon Vilar (Department of Chemistry, ICL)

Professor Marina Kuimova (Department of Chemistry, ICL)

Abstract:

Proteins can undergo liquid-liquid phase separation (LLPS) and form liquid droplets. This selfassembly mechanism plays a central role in biology and disease (e.g. Alzheimer’s and Parkinson’s disease). Nevertheless, it is still largely uncharacterised due to the lack of analytical tools to monitor it in biologically relevant complex systems, such as cells. Environmentally responsive probes offer unparalleled opportunities to probe biomolecular self-assembly events in cells and provide a read-out for their location, timing, and downstream consequences.

In this project, we will deliver a platform to quantitatively monitor LLPS in live cells, for the first time. We will investigate ɑ-synuclein, a crucial protein of the nervous system, whose LLPS has been hypothesised to be important for the protein’s normal function and for inducing amyloid aggregation linked to Parkinson’s disease. This multidisciplinary project will involve a combination of biophysical protein characterisation, optical probe development and live cell microscopy.

Recruitment will continue until the post is filled.

Eligibility:

The entry requirement is a degree in the physical sciences with a minimum 2.1 or above (or equivalent). Chemistry, physics, mathematics and engineering graduates who wish to learn how to apply their physical sciences skills to biological problems.

Students from biological or medicinal backgrounds are usually not eligible. If in doubt, please contact us.

We are able to accept both ‘Home’ fee status and ‘Overseas’ fee status applicants for this project. Please see our Eligibility Criteria webpage for more detailed information.

About the ICB CDT

Successful applicants to this project will be part of 2023 entry cohort of the EPSRC CDT in Chemical Biology: Innovation for the Life Sciences. The aim of the ICB CDT, one of the longest standing CDTs in the UK, is to train students in the art of multidisciplinary Chemical Biology research, giving them the exciting opportunity to develop the next generation of molecular tools and technologies for making, measuring, modelling and manipulating molecular interactions in biological systems.

Applicants to this programme will enrol on a 1 year MRes in Chemical Biology and Bioentrepreneurship, followed by a 3 year PhD, building on the research project from the MRes. For further information, please see our studentship webpages.

Successful applicants, both Home and International, will be awarded a fully funded studentship. This includes:

• Annual National Minimum Doctoral Stipend, currently £17,668 + £2000 London allowance for 2022/23
• Annual Tuition fees at either the Home or Overseas fee rate for both the MRes and PhD years
• A Research Training Support Grant for laboratory consumable costs of £3,500 per year
• Funding to attend conferences
• Transferable skills training

How to apply

To apply for this project, please submit an application on the Imperial College Gateway (please see our How to Apply page for more detailed guidance).