Towards understanding the molecular interactions in biological membranes: a functional approach by solid-state NMR. (360G-Wellcome-079599_Z_06_Z)

Characterisation of the molecular interactions that occur within biological membranes is vital if we are to understand the myriad of processes they support. The research proposed intends to exploit the unique and recent potential of solid-state NMR to study biological membranes without extraction of the individual components and under near physiological conditions. My goal is to provide dynamic and structural information regarding protein/protein andprotein/lipid interactions occurring within the bilayer and their modulation by small molecules. Initially this will focus on: 1) Characterisation of molecular contacts in biomembranes. This research studies the interaction of anaesthetics at the lipid/protein interface of the nicotinic acetylcholine receptor, a protein readily purified from T.nobiliana. Exploiting the favourable NMR properties of protons we aim to characterise the interface between these molecules at a molecular level, providing key structural data for rational drug design.2) Analyse the effect of bilayer composition on the lateral segregation, structure and oligomeric state of membrane proteins and investigate its role in protein trafficking. Systematically applying multidimensional magic-angle spinning and oriented sample NMR techniques together with diffusion measurements I aim to study these effects on Fukutins to understand how interactions with the lipid bilayer regulates their trafficking.