A team of academics from The University of Warwick and Aston University has secured a £1.8m grant to produce membrane proteins which will support sustainable manufacturing and drug discovery.
The funding from the UKRI Technology Missions Fund will be used to engineer microbial cell factories to produce membrane proteins to support drug screening and the production of sustainable chemicals.
The team will primarily focus on overcoming the identification of cellular production bottlenecks and stresses and the membrane environment that surrounds the proteins.
Dr Doug Browning, Lecturer in Biosciences at Aston University, said: “This funding, in conjunction with our industrial partners, will enable us to design and construct new expression systems that will produce high-value membrane therapeutics, which can be used in the fight against many important medical diseases.”
Why are membrane proteins important?
Membrane proteins are vital molecules on the surface of cells with a number of biological functions, for example, sensing hormones or cell communication.
They are targeted by the top-selling medicines worldwide and multiple vaccines, including those for COVID-19, Hepatitis B, and whooping cough.
New drug molecules that can change protein function can also be identified through their manufacture and purification.
Applications of membrane proteins
Some membrane proteins are useful as catalysts to produce sustainable chemicals. Some membrane enzymes, for example, can be used to fix carbon.
The membranes react with carbon dioxide from the air, enabling cells to turn into useful chemicals that can be used as feedstocks in biomanufacturing processes.
Others can be used to degrade plastics.
Challenges with large-scale production
Despite their importance, engineering the production of high levels of membrane proteins is challenging. This is because the complex processes of membrane production place large amounts of stress on the cells.
The efficiency of drug screening is limited by this stress, thereby reducing the chances of discovering new drugs.
Adoption of new technologies
The team will combine computational whole-cell models and molecular dynamics simulations with molecular biology and biochemistry tools to engineer microbial cell factories. These factories will be able to self-regulate their protein production in response to stress and have the optimal membrane environment to support protein function.
The new technologies will increase the yields of high-quality functional proteins, simplifying the time required to produce key biomedical proteins for drug screening.
Professor Phillip Stansfeld, School of Life Sciences, University of Warwick, concluded: “With the recent computational revolution in protein-structure prediction and design approaches, it is timely to study the dynamics of computationally-optimised membrane proteins and develop approaches to rationally escalate their structural determination.”
