Molecular interactions in biological membranes
Biological membranes are ubiquitous in nature and play a vital role in defining the interface of the cell with its environment and its intracellular compartmentalisation. In order to facilitate the transfer of information and materials across these barriers cells have evolved families of integral membrane proteins. The goal of our research is to understand the function of these proteins in their native lipid environment and for this purpose; we are developing solid-state NMR techniques which enable us to probe the structure and dynamics of these systems at an atomic level. In conjunction with other biophysical techniques, this method allows us to characterise how membrane proteins interact with other proteins, the surrounding lipids and other small molecules and to determine how these interactions modulate their function.
Recognition of small molecules by integral membrane receptors
The regulation of many integral membrane receptors is mediated through their interaction with small molecules. Our studies on the nicotinic acetylcholine receptor have enabled us to identify interactions involved in ligand binding and determine the conformation of the bound agonist, acetylcholine. Currently we are developing further solid-state NMR techniques to analyse how hydrophobic ligands such as anaesthetics may interact with the nicotinic acetylcholine receptor and aid in the rational development of pharmaceuticals against both this and other classes of membrane proteins.
Regulation of protein trafficking
The targeting of integral membrane proteins to the appropriate organelle or region at cell surface is vital to their function in eukaryotic cells. It is proposed that interactions between lipids and integral membrane proteins may play an important role in regulating this targeting process. Exploiting the potential of solid-state NMR techniques to study the structure of integral membrane proteins under near physiological conditions, we hope to be able to determine how bilayer composition and lateral phase separation may regulate the structure, oligomeric state and localization of integral membrane proteins and determine the role that this may play in regulating intracellular protein trafficking. These studies may provide molecular insights into a range of diseases linked to the mistrafficking of proteins.
A number of diseases important to modern society including Alzheimer’s, Parkinson’s and Huntington’s are characterised by the deposition of proteins as insoluble aggregates within the body. Solid-state NMR provides us with a unique opportunity to probe the structure of these aggregates at a molecular level. Currently we are employing solid-state NMR in conjunction with other biophysical techniques to characterise the structural transitions that result in the formation of these deposits. These studies are providing us with valuable insights into the onset and progression of these diseases and ascertaining the role other in-vivo factors may play in these diseases.
Nuclear Magnetic Resonance (NMR)
Molecular and Cellular Biosciences
Affiliate research group(s)
Institute for Complex Systems Simulation (ICSS)
Using a range of biophysical techniques we are investigating how the lipid composition of the intracellular compartments affects protein structure and the role this may play of intracellular localisation.
Using a combination of liquid and solid-state NMR spectroscopy we aim to understand how serum amyloid-P component recognises amyloid fibrils and the role this plays in their stabilization.
Dr Philip Williamson
Faculty of Natural & Environmental Sciences
Life Sciences Building 85
University of Southampton
Telephone:(023) 8059 4350