Mycotic infections are ubiquitously distributed geographically and amongst individuals of all age groups. Recent reports indicate that systemic mycoses will continue to be a major health problem and actually increase as immunosuppressive therapies proliferate attendant to treatment of patients with malignant and immunologically related diseases or with organ transplants. The major chemotherapeutic drugs currently employed, and those in experimental and developmental programs, have as their principal target some aspect of the sterol physiology of the fungi. It is clear that the distinctive sterol structures and functions in the fungi represent particularly vulnerable targets for controlling fungal growth. The proposed research is a basic program of study of the sterols in fungi. Yeast have been shown to be a nearly ideal system for this work. The long term goal is to identify cellular reactions that are unique to the fungi or are especially amenable to therapeutic control. The objective of the requested grant is to develop an understanding of sterol biosynthesis and metabolism and to study their physiological function and control. It is anticipated that this information will be of use in the development of specific controlling agents for various pathogenic fungi.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK037222-08
Application #
3235997
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Project Start
1985-09-01
Project End
1995-03-31
Budget Start
1993-04-01
Budget End
1994-03-31
Support Year
8
Fiscal Year
1993
Total Cost
Indirect Cost
Name
North Carolina State University Raleigh
Department
Type
Schools of Earth Sciences/Natur
DUNS #
City
Raleigh
State
NC
Country
United States
Zip Code
27695
Crowley, J H; Tove, S; Parks, L W (1998) A calcium-dependent ergosterol mutant of Saccharomyces cerevisiae. Curr Genet 34:93-9
Smith, S J; Parks, L W (1997) Requirement of heme to replace the sparking sterol function in the yeast Saccharomyces cerevisiae. Biochim Biophys Acta 1345:71-6
Crowley, J H; Smith, S J; Leak, F W et al. (1996) Aerobic isolation of an ERG24 null mutant of Saccharomyces cerevisiae. J Bacteriol 178:2991-3
Smith, S J; Crowley, J H; Parks, L W (1996) Transcriptional regulation by ergosterol in the yeast Saccharomyces cerevisiae. Mol Cell Biol 16:5427-32
Parks, L W; Smith, S J; Crowley, J H (1995) Biochemical and physiological effects of sterol alterations in yeast--a review. Lipids 30:227-30
Casey, W M; Gibson, K J; Parks, L W (1994) Covalent attachment of palmitoleic acid (C16:1 delta 9) to proteins in Saccharomyces cerevisiae. Evidence for a third class of acylated proteins. J Biol Chem 269:2082-5
Crowley, J H; Lorenz, R T; Parks, L W (1994) Fenpropimorph affects uptake of uracil and cytosine in Saccharomyces cerevisiae. Antimicrob Agents Chemother 38:1004-7
Casey, W M; Rolph, C E; Tomeo, M E et al. (1993) Effects of unsaturated fatty acid supplementation on phospholipid and triacylglycerol biosynthesis in Saccharomyces cerevisiae. Biochem Biophys Res Commun 193:1297-303
Smith, S J; Parks, L W (1993) The ERG3 gene in Saccharomyces cerevisiae is required for the utilization of respiratory substrates and in heme-deficient cells. Yeast 9:1177-87
Lorenz, R T; Parks, L W (1992) Cloning, sequencing, and disruption of the gene encoding sterol C-14 reductase in Saccharomyces cerevisiae. DNA Cell Biol 11:685-92

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