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Biosynthesis, remodeling and intracellular transport of GPI proteins and sphingolipids in yeast

English title Biosynthesis, remodeling and intracellular transport of GPI proteins and sphingolipids in yeast
Applicant Conzelmann Andreas
Number 116802
Funding scheme Project funding (Div. I-III)
Research institution Division de Biochimie Département de Biologie Université de Fribourg
Institution of higher education University of Fribourg - FR
Main discipline Biochemistry
Start/End 01.04.2007 - 31.03.2010
Approved amount 605'000.00
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Keywords (6)

GPI anchors; remodeling; sphingolipids; membranes; phospholipids; very long chain fatty acids

Lay Summary (English)

Lay summary
Lipids contained in the membranes of eukaryotic cells have numerous functions. They form the basic lipid bilayer which, together with membrane proteins, constitutes the cellular membranes. These membranes are impermeable to most molecules and allow the cells to protect their internal milieu from changes in the surroundings, as well as to allocate their own contents to different membrane enclosed compartments (organelles). Beyond this barrier function, membranes are ordering platforms for complex molecular events. The lipids forming a membrane fall into countless structurally different classes and membranes from different cells or organelles contain very different lipid profiles. Cells alter their lipid profile during physiological responses to stresses and, in spite of the usually very high later diffusion rates, lipids also are not uniformly distributed in the plane of the membrane. This allows to accommodate and concentrate proteins into special membrane domains, thus enhancing their mutual interaction or activity. Our present research focuses on the study of several lipid biosynthetic enzymes, the activity of which can be measured by appropriate biochemical assays, but for the corresponding genes are not yet known. Some of the enzymes we are studying are exchanging lipid moieties of so called glycosylphosphatidylinositol (GPI) anchored membrane proteins while these proteins travel through the secretory pathway. The GPI proteins are found at the surface of about every eukaryotic cell and we have so far identified 2 genes which are involved in these modification reactions. While all our studies are carried out in baker's yeast which represents an excellent model system, we recently have begun to study similar processes in human pathogens such as trypanosoma brucei, trypanosoma cruzi and aspergillus fumigatus. Other genes of interest are genes synthesizing glycerophospholipids, equally not identified. We further study known and unknown proteins, which synthesize sphingolipids. All enzymes we study consist of integral membrane proteins and we are interested not only in determining their catalytic centers, but also in the orientation of these centers with regard to the plane of the membrane. The orientation of these catalytic centers dictates the compartment/organelle from which the substrates are taken and into which the products are released.At the moment, the bulk of our studies have to be classified as purely fundamental research and of no predictable benefit for human disease, ecology or economy. We however are convinced that the complete annotation of the yeast and human genomes and metaboloms, i.e. the complete listing of at least some functions for all gene products and of the gene(s) for all measurable functions will open new perspectives and will allow to better understand and predict biological processes.
Direct link to Lay Summary Last update: 21.02.2013

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Associated projects

Number Title Start Funding scheme
131078 Biosynthesis, remodeling and intracellular transport of GPI proteins and sphingolipids in yeast 01.04.2010 Project funding (Div. I-III)
67188 Biosynthesis, remodeling and intracellular transport of GPI anchored proteins in yeast 01.04.2002 Project funding (Div. I-III)