• Led by Aston University’s Dr Alice Rothnie, the researchers will develop a polymer-lipid particle technique to extract cell membrane proteins
• By preserving the protein structure better, the method will lead to better drug discovery and testing for diseases such as cancer and diabetes
• The network includes Kings College London, Imperial College, Diamond Light Source, the University of Birmingham and the University of Leeds.

A project at Aston University to extract proteins from cell membranes for better drug discovery and testing has won a Biotechnology and Biological Sciences Research Council (BBSRC) Network grant of £345,000.

BBSRC gives Network grants to establish and support a new collaborative research network. The IMPALA-NET (Integral Membrane Proteins And Lipid Assemblies NETwork UK) project will be led by Dr Alice Rothnie, a reader at Aston University School of Biosciences. The network includes researchers at Kings College London, Imperial College, Diamond Light Source, the University of Birmingham and the University of Leeds. IMPALA-NET is associated with the Aston Institute for Membrane Excellence (AIME), a multidisciplinary research institute combining membrane protein biochemistry and polymer science.

The researchers say that their research could lead to much more efficient and accurate drug discovery programmes and the development of new medicines to treat all kinds of diseases and conditions, such as cancer, inflammatory conditions, cardiovascular disease, genetic diseases and diabetes, as well as for pain relief and novel antimicrobials. With a blockbuster drug potentially worth billions of pounds, IMPALA-NET’s research, as well as improving the health and lives of millions of people, could have significant benefit for UK businesses and the UK economy. It will also develop the next generation of researchers in the field.

Proteins on the surfaces of cell membranes have many functions, including importing nutrients and cell communication. Around half of all drugs worldwide target cell membrane proteins. To understand how these membrane proteins work or to identify and test potential drugs and their actions on a membrane protein, it is necessary to separate them from the cell membrane, which is a fatty lipid bilayer. Conventionally, this has been done with detergents, but while detergents successfully remove the proteins, they also destroy the surrounding lipids, which are important for the proteins’ structure and function.

IMPALA-NET will develop polymer-lipid particles (PLPs) as an alternative. PLPs are nanoparticles made from a synthetic polymer that can cut out nano-sized patches of the cell membrane, containing membrane proteins and the fatty lipid molecules that surround them. The polymer wraps around the outside to stabilise the particle. This means the proteins stay in a more ‘natural’ state, so will react to a drug in a more realistic way when tested. This will result in a much higher likelihood of finding effective medications.

PLP technology has huge promise, but there are big gaps in the knowledge of how to use the particles. This is where a network like IMPALA-NET comes in. The multidisciplinary and diverse network of researchers will be able to share ideas, challenges and best practice to help close the knowledge gaps and apply PLP technology, as well as generate resources to share with the wider research community.

IMPALA-NET will include polymer chemists, computational scientists and others with the necessary skills to improve the polymers themselves to offer bespoke design, for example to make a PLP suitable for a specific technique, or optimised for a specific protein.

Dr Rothnie said:

“We are aiming to bridge the gap between academia and industry by determining precise industry needs and co-creating standardised, industrially reproducible approaches to PLPs, as well as retain expertise and continuity within the research community by providing career development opportunities to early career researchers. Achieving these objectives would pave the way for PLPs to be routinely used within both academia and industry.

“I’m excited about establishing this network and bringing together researchers across the UK to share findings so that we can start to fully exploit the potential of polymer lipid particles for membrane protein studies. Success stories are well published, but what often isn’t shared are the things that don’t work, so creating a forum where people can share and work together to overcome the challenges should provide a way to really progress the research.”