The main topics to be addressed are:
* What is the physiological role for lipoprotein lipase (LPL) and/or hepatic lipase (HL) as ligands for binding and metabolism of chylomicrons/remnants in the liver and other tissues?
* Which receptors are most important for this process and what are the molecular details of the interactions?
* What are the relative roles of lipolysis and particle uptake for lipid transport with chylomicrons and for partitioning of fatty acids and other lipids among tissues?
* What are the molecular pathways for regulation and tissue-specific expression of the LPL and HL genes? What is the basis for the cell and tissue localisation of the enzymes?
* Are lipoproteins, lipases and receptors internalised as complexes by liver and other cells?
* What is the impact of genetic variation in lipase, apolipoprotein and receptor genes on lipid metabolism and cardiovascular disease?
The project will utilise a wide variety of techniques of modern biomedical research. For this, the expertise of the collaborating laboratories shall complement rather than duplicate each other. Most studies will be at the level of molecular biology, cell culture, or test tube biochemistry, but there will also be organ perfusion, animal experiments and clinical genetic studies in human populations. Reagents will be developed and shared among the collaborating laboratories, such as cDNA probes, specific antisera, constructed and/or natural mutant variants of lipases, apolipoproteins and receptors, as well as genetically engineered cells and mice.
The project will be implemented through collaboration and co-ordination between independent laboratories on an equal basis. All participants have joint research projects with at least one of the other laboratories. The main objective is to extend and intensify the exchange of personnel, materials and ideas.
There will be a meeting of representatives from all participating groups at least once every year. A major avenue to deepened collaboration will be periods for work and training in partner laboratories for younger group members, at the graduate student and post-doc levels. These periods will typically be for three months.
Another objective will be to provide opportunities for established members to work for periods of a few days or weeks in another participating laboratory. The Umeå laboratory will act as co-ordinating centre.
Heparan sulphate, triglyceride, cholesterol, chylomicron, endothelium, secretion, gene expression, regulation, transgenic mice, adipose tissue.