An analysis of regulation of phospholipid synthesis will be conducted in the unicellular eukaryotic organism, Saccharomyces cerevisiae. The studies will involve isolation and characterization of mutants with defects in the synthesis and/or regulation of phospholipids. The mutants will be employed in regulatory studies and they will be used to facilitate the cloning of structural genes encoding membrane associated enzymes of phospholipid biosynthesis. The cloned genes will be employed in studies of the regulation of phospholipid synthesis in response to exogenous precursors, such as inositol and choline. The cloned genes will also be used to facilitate studies of the assembly of these proteins into their specific locations in the cellular membranes. Little is known about the mechanisms by which eukaryotic cells control the synthesis of membrane lipids in coordination with ongoing membrane biogenesis. Yet phospholipids, particularly inositol containing phospholipids have been implicated in complex signalling processes which play a role in controlling cell growth and proliferation in higher eukaryotes. Yeast cells synthesize a typically eukaryotic mixture of phospholipids, using pathways which are similar to those in higher eukaryotes. The organism is genetically tractable, and can be manipulated using a powerful molecular genetics. Therefore, S. cerevisiae presents an unusual opportunity to develop a comprehensive understanding of the regulatory mechanisms controlling phospholipid synthesis during membrane biogenesis and cell growth in a simple eukaryote.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM019629-17
Application #
3269706
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Project Start
1987-09-01
Project End
1991-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
17
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Carnegie-Mellon University
Department
Type
Schools of Arts and Sciences
DUNS #
052184116
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Gaspar, Maria L; Chang, Yu-Fang; Jesch, Stephen A et al. (2017) Interaction between repressor Opi1p and ER membrane protein Scs2p facilitates transit of phosphatidic acid from the ER to mitochondria and is essential for INO1 gene expression in the presence of choline. J Biol Chem 292:18713-18728
Mondo, Stephen J; Lastovetsky, Olga A; Gaspar, Maria L et al. (2017) Bacterial endosymbionts influence host sexuality and reveal reproductive genes of early divergent fungi. Nat Commun 8:1843
Lastovetsky, Olga A; Gaspar, Maria L; Mondo, Stephen J et al. (2016) Lipid metabolic changes in an early divergent fungus govern the establishment of a mutualistic symbiosis with endobacteria. Proc Natl Acad Sci U S A 113:15102-15107
Barneda, David; Planas-Iglesias, Joan; Gaspar, Maria L et al. (2015) The brown adipocyte protein CIDEA promotes lipid droplet fusion via a phosphatidic acid-binding amphipathic helix. Elife 4:e07485
Han, Sungwon; Binns, Derk D; Chang, Yu-Fang et al. (2015) Dissecting seipin function: the localized accumulation of phosphatidic acid at ER/LD junctions in the absence of seipin is suppressed by Sei1p(?Nterm) only in combination with Ldb16p. BMC Cell Biol 16:29
Henry, Susan A; Gaspar, Maria L; Jesch, Stephen A (2014) The response to inositol: regulation of glycerolipid metabolism and stress response signaling in yeast. Chem Phys Lipids 180:23-43
Hofbauer, Harald F; Schopf, Florian H; Schleifer, Hannes et al. (2014) Regulation of gene expression through a transcriptional repressor that senses acyl-chain length in membrane phospholipids. Dev Cell 29:729-39
Lee, Sojin; Gaspar, Maria L; Aregullin, Manuel A et al. (2013) Activation of protein kinase C-mitogen-activated protein kinase signaling in response to inositol starvation triggers Sir2p-dependent telomeric silencing in yeast. J Biol Chem 288:27861-71
Aung, Hnin W; Henry, Susan A; Walker, Larry P (2013) Revising the Representation of Fatty Acid, Glycerolipid, and Glycerophospholipid Metabolism in the Consensus Model of Yeast Metabolism. Ind Biotechnol (New Rochelle N Y) 9:215-228
Henry, Susan A; Kohlwein, Sepp D; Carman, George M (2012) Metabolism and regulation of glycerolipids in the yeast Saccharomyces cerevisiae. Genetics 190:317-49

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