Membrane protein driven, active metabolite transport in durable vesicle compartments as artificial organelles for biotechnology

Artificial cells and organelles are seen as a stepping-stone to understanding the origin of life and are being developed to generate novel cell-like biotechnologies. They are typically vesicles made from phospholipids, which have a short lifespan. In this project you will use principles of synthetic biology to enhance the stability of protocells by creating hybrid bionic systems that combine advantages of lipid and polymer vesicles. Incorporation of membrane proteins will provide essential metabolite transport into (or out of) the vesicle lumen as biochemical signals and reaction substrates. Such systems will have broad-ranging applications, including development of ultrasmart metabolite-responsive drug delivery systems for treatment of diseases such as cancer.

You will build on recent advances in hybrid vesicles as a durable membrane protein reconstitution system: we recently demonstrated a tenfold increase in functional lifetime of a respiratory enzyme (cytochrome bo3) compared to conventional proteoliposomes. This project will focus on metabolite transporters for essential substrate transport and concentration inside vesicle nanoreactors. Membrane proteins for generating proton motive forces of opposite polarities across the hybrid vesicle membrane (cytochrome bo3; pyrophosphatases). These will be coupled with proton symporters (GalP) and antiporters (AceI) to concentrate their substrates inside the vesicles. Expertise in a broad range of transporter proteins is available in the supervisory team.

You will learn skills in expression, purification, reconstitution and functional characterization of membrane proteins. Advanced biophysical characterization techniques including confocal microscopy and cryo-TEM will be applied to gain detailed insights into the behaviour of these proteins in hybrid membranes.

Information on how to apply can be found at: https://biologicalsciences.leeds.ac.uk/research-degrees/doc/how-to-apply