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Title: Phosphatidylinositol transfer proteins : does the topology and the stored curvature elastic stress of lipid bilayers regulate membrane-association and lipid abstraction?
Author: Goehring, Natalia
ISNI:       0000 0004 2712 5751
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2012
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Lipids in a bilayer determine the stresses and the topology of the membrane they form. An understanding of the link between lipid composition and biomechanical parameters such as the spontaneous curvature and bending rigidity is key to elucidate the mechanisms behind protein‐membrane interactions. Despite their relatively low abundance in‐vivo, one of the most important class of lipids involved in signalling cascades in cells are the phosphatidylinositols (PIs) lipids. Experimental studies of the effect of phosphatidylinositol lipids upon model and cellular membrane systems remain in their infancy and have not matched the pace of discovery with respect to their role in regulating key cellular processes. Synthesised at the endoplasmic reticulum, one route for the distribution of the PIs to other organelle membranes is via translocation by the phosphatidylinositol transfer proteins (PITP). In order to study the link between membrane composition and PITP function, these proteins have been assayed for their interaction and binding with model membranes containing differing amounts of PI. Corresponding studies of the phase behaviour of these systems have been conducted using Small Angle X‐ray scattering specifically investigating the influence PI has in a bilayer membrane formed by dioleoylphosphatidylcholine, as well as in an inverted hexagonal phase formed by dioleoyl‐phosphatidylethanolamine. Additionally, a novel platform based upon a BODIPY fluorescent probe is presented, which is able to sense the stored stresses within lipid bilayers, and whose measurements are correlated these with the make‐up of membranes.
Supervisor: Ces, Oscar Sponsor: EPSRC
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral