Towards an Understanding of the Effect of Glycolipid Structure on Biological Function

The immune system is capable of responding to a wide range of molecular stimuli, to produce a specific immune response. Whilst much of the immunology literature has focused on the role of peptide antigens in generating an immune response, a set of T cells known as invariant Natural Killer T-cells (iNKT-cells) are activated by a very different class of molecules, namely lipids. The mechanism of activation involves a protein known as CD1d, which binds a range of lipids, including glycolipids. The objective of this project is to elucidate the mechanism by which promising glycolipid drug molecules interact with cell membranes and with the proteins that extract them from membranes. A range of physical probes will be used (microscopy, vibrational spectroscopy and reflectivity). The project will involve the synthesis of candidate molecules, including labelled molecules, and a study of their interactions with model cell membranes. The results will inform the future rational design of therapeutic molecules to target a range of diseases in mammals.