Membrane proteins are integral to novel therapeutics, but difficult to characterise structurally.
Academics from the UK’s Aston University and the University of Warwick have received funding of £1.8 million to develop processes for the manufacture of membrane proteins via microbial cell factories.
The membrane proteins will be used in future drug screening and sustainable chemical production. The funding came from the UK Research and Innovation (UKRI) Technology MIssions Fund, which is aimed at exploiting the UK’s leadership in technologies to solve specific problems.
Membrane proteins can be used in pharmacology to identify new drug molecules that may inhibit or activate protein function. Some membrane proteins can also be used as catalysts to produce sustainable chemicals. One area of application is the fixing of carbon, reacting with carbon dioxide from the air and using membrane enzymes to turn it into useful chemicals that can be used as feedstock for biomanufacturing processes. Others could be used to degrade plastics.
However, engineering the production of functional membrane proteins is challenging due to biological and technological complexity of the processes involved in their manufacture, which places a large amount of stress on cells. In the area of pharmacology this can limit the efficiency of drug screening and reduce the chances of discovering new drugs. The research will focus on the identification of cellular production bottlenecks and cellular stresses, along with the membrane environment that surrounds the proteins.
‘Membrane proteins are integral to both life and the development of novel therapeutics, however, these proteins remain difficult to characterise structurally,’ said Professor Phillip Stansfeld, School of Life Sciences University of Warwick.
‘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,’ he added.
The research teams will combine computational whole cell models and molecular dynamics simulations with molecular biology and biochemistry tools to engineer microbial cell factories that can self-regulate their protein production in response to stress and have the optimal membrane environment to support protein function.
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