• Misfolded membrane proteins in cells are implicated in many diseases including cystic fibrosis, diabetes, Alzheimer's and Parkinson's
• Dr Grant Pellowe will lead fundamental research to understand the rules of how membrane proteins fold correctly
• Eventually the research could lead to new ways to correct misfolding as the proteins are made in the body

Aston Institute for Membrane Excellence (AIME) has won a £438,674 Research Project Grant from the Leverhulme Trust to carry out fundamental research into how membrane proteins fold correctly.

The proteins that make up the body are made at membranes in cells in long chains of individual building blocks, called amino acids, which then must fold into the correct 3D fatty membrane shape. The folded membrane protein travels to another membrane to carry out a specific task, for example, transporting water or a particular ion, across the cell membrane or communication. However, when the protein misfolds, it cannot interact with other proteins, molecules and membranes correctly, and so cannot carry out its task, leading to serious problems for the cell. These misfolded, malfunctioning proteins are a cause of many diseases including cystic fibrosis, diabetes, Alzheimer's and Parkinson's.

How these protein chains fold into their shape is not well understood, and the key players and mechanisms driving this process remain unclear. AIME’s Dr Grant Pellowe will lead research to examine each step proteins go through as they fold, and how the genetic sequences and the cellular environment influence this process.

To do so, Dr Pellowe and his team will isolate membrane proteins during the folding process and analyse each of these intermediates using advanced experimental techniques, including mass spectrometry and structural spectroscopy. At each step, they will examine how the membrane proteins interact with chaperones (specific proteins that assist in the folding of other proteins) and membrane lipids.

Dr Pellowe explains that the research aims to determine whether proper protein folding is inherently encoded within the amino acid sequence itself, and to what extent and how external factors, such as chaperone proteins and the surrounding membrane or lipid environment, also influence the folding process.

Armed with this knowledge, researchers in the future will be able to address misfolded proteins as they are being made to mitigate and treat disease. They could also potentially design or alter proteins to get more protein material for industrial processes such as drug testing.

Dr Pellowe said:

“This area of research holds particular significance for the academic community, as it addresses a critical gap in molecular and cellular biology. Around 15 to 25% of disease-causing mutations are thought to result from protein misfolding. To advance both basic science and therapeutic development, we must first understand how folding normally occurs within cells. This foundational knowledge will allow researchers to uncover how misfolding contributes to disease and to design new strategies that target the specific stages where folding goes wrong.”

The Leverhulme Trust is an independent charity that seeks to fund blue skies research and scholarship which has the potential to generate new ideas and research breakthroughs that benefit society. It awards Research Project Grants for researchers based at universities or institutions of higher education, to undertake an innovative and original research project.