IMPALA-NET UK: Integral Membrane Proteins And Lipid Assemblies NETwork UK

Context Membrane proteins are vital for life. They sit in the outer layer of cells, and carry out vital roles such as importing nutrients, exporting toxins/waste and facilitating communication between different cells in the organism. Approximately half of all drugs target membrane proteins, and they are potential targets for many more conditions. However, to develop new drugs it is necessary to purify the membrane proteins away from the rest of the cell. Traditionally this was achieved using detergents to disrupt the fatty environment of the membrane proteins and make them soluble in water, but this process strips the proteins of their natural environment, which can affect their structure and stop them working properly. This means that drug screening will not work effectively so new approaches are needed. Polymer lipid particles (PLPs) offer an alternative option to detergents. PLPs extract nano-sized patches of the cell membrane, containing membrane proteins and the fatty lipid molecules that surround them, which enables purification of membrane proteins whilst retaining a native-like environment. This is important because it provides a much better representation of the protein within the cell for testing new therapies and a higher likelihood of finding new drugs. The challenges & objectives: Despite the great potential offered by PLPs, there remain several knowledge gaps that hinder exploitation of this influential technology, and there is a lack of cohesive information available for researchers wishing to start working with this approach. This is particularly acute within the industrial sector. To address these limitations IMPALA-NET proposes to: Bring together UK experts in the application of PLPs, to share findings, expertise and solutions to existing and future challenges, generating resources to share with the wider research community, Incorporate polymer chemists, computational scientists and others with the necessary skills to drive improvement in the polymers themselves to offer bespoke design, Bridge the gap between academia and industry by determining precise industry needs and co-creating standardised, industrially reproducible approaches to PLPs, enhancing economic development for UKplc. Retain expertise and continuity within the research community by providing career development opportunities to ECRs. Potential applications & benefits Achieving these objectives would pave the way for PLPs to be routinely used within both academia and industry. This would lead to improved scientific knowledge of membrane protein structure and function, the use of PLPs in drug discovery programmes, and potentially the development of novel therapeutics. This will have significant economic benefit for UK businesses (“blockbuster” drug can be worth £billions), will help develop the next generation of researchers within the area and impact the general public though improved treatments. Relevance to BBSRC priorities IMPALA-NET seeks to ‘enable innovation and working with business’, forming collaborations across bioscience disciplines and other fields, such as the physical sciences and engineering, to further develop and exploit the potential of PLPs. This technology has the potential to enable new mechanistic understanding of membrane proteins, improving our ‘understanding of the rules of life’, as well as developing novel approaches and therapeutics to improve health and wellbeing.