Objective
To develop a new approach to study glycerophospholipid (GPL) metabolism in brain cells.
To study biologically occurring GPLs at the molecular level under near-to-physiological conditions.
To study whether phenothiazines alter lipid-mediated signalling by intercalation among GPLs in membranes of neuroblastoma cells.
The effect of membrane structure on cell-signalling enzymes derived from brain sources will be studied as a function of the fatty acid composition of membrane glycerophospholipids (GPLs). This novel approach differs from most conventional GPL studies which consider only head group specificity. The most widely studied signal pathways involve GPLs, specifically the polyphosphoinositides (PPIs) and phosphatidyl-choline (PC). Before their role in signalling was known, GPLs in general were thought to be alike and metabolically active. However, recent work has shown that not only do some GPL classes have much higher turnover rates than others, but even within a given GPL class certain subclasses, molecular species (same head group, but diffent acyl groups), have unique turnover patterns as shown by radiolabelling studies.
Because enzyme-substrate molecular species specificity cannot be reproduced in in vitro studies with the currently used techniques, mostly detergent solubilisation, it is suggested that the activity of membrane-bound enzymes can be modulated not only by GPL class, but also by the fatty acid composition and organisation (packing) of the "bulk" GPL phase in the membrane. The activities of individual enzymes in the PPI and PC will be studied in model membranes (liposomes and monolayers) of defined molecular species and concentrations. The model membranes will be characterised by many physicochemical methods and parallel experiments will be carried out in neuronal cell lines and platelets.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences cell biology cell signaling
- natural sciences biological sciences biochemistry biomolecules lipids
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Coordinator
5009 Bergen
Norway
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