Glycosphingolipid catabolism and transfer in health, disease and immunity. (360G-Wellcome-093757_Z_10_Z)

1) To investigate the molecular mechanism of lipid binding and solubilisation by saposin molecules. 2) To reveal the molecular mechanism by which saposins A and C present substrate and activate GalC. 3) To fully investigate the consequences of known clinical mutations on GalC stability, activity, cellular location/trafficking and interaction with substrate, membranes and saposins. Can these parameters be affected in vitro and in vivo by inhibitor or chaperone binding? (In collaboration with Prof. Paul Luzio) 4) To reveal the molecular mechanism by which saposins load lipid antigens onto CD1d and CD1b molecules. To test the hypothesis that saposins mediate loading of specific myelin-related autoantigens, and determine whether autoreactive T cells or NKT cells exist in patients with Krabbe disease and Multiple Sclerosis (In collaboration with Prof. Timothy Cox).