FP6 priority

1.1.1   Genomics and Biotechnology for Health

1.1.2.1
1.1.1

Title of the proposal

Fungal membranes as the target in antimycotic therapy

Institute

Slovak Academy of Sciences, Institute of Animal Biochemistry and Genetics
Moyzesova 61, 900 24 Ivanka pri Dunaji, Slovak Republic

Contact

Research subject for a potential FP6 project

Mycoses represent currently a major problem in human medicine.The effective use of anti-mycotics is limited by several factors, e.g. lack of drugs with selective antifungal activity, the development of resistance to commonly used antifungal compounds and frequent predominantly fungistatic effect of many antimycotics. The high-throughput approach of combinatorial chemistry is providing new classes of substances with potentially antimycotic activity and their testing in appropriate fungal models will be probably the limiting step. Membrane lipids (particularly sterols) represent the target for the activity of he majority of clinically relevant antimycotics and they will probably preserve their importance in the area of antimycotic treatment also in the future. Our laboratory is interested in the regulation of membrane lipid biogenesis in yeast for more than a decade. We believe that a project proposal integrating the power of genomics and proteomics in the identification of new targets for antifungal treatment with the functional analysis of mechanisms and regulation of membrane biogenesis in yeast might be interesting for several laboratories across the Europe. Such a project could bring principally new information about the adaptation of fungal pathogens to antimycotic-induced stress and might have a direct impact on the strategy of combating human mycoses. The contribution of our laboratory to these efforts might include various aspects of lipid metabolism and intracellular lipid trafficking (cell frac-tionation, quantitative analysis of membrane lipid composition, regulation of lipid biogenesis including gene expression studies, etc.) and phenotypic analysis in the screening for new targets in antimycotic therapy.

Recent international cooperation of the research team

Institute of Biochemistry, Technical University Graz, Austria
Institute of Molecular Biology, Biochemistry and Microbiology, Karl Franzens University Graz, Austria
Institute of Microbiology, Czech Academy of Sciences, Prague, Czech Republic

Proposer´s relevant publications related to the research subject

Hapala, I. (1997). Breaking the barrier: Methods for reversible permeabilization of cellular membranes. Crit. Rev. Biotechnol. 17, 105-122.
Sreenivas A., Patton-Vogt J. L., Bruno V., Griac P., Henry S. A (1998). A role for phospholipase D (Pld1p) in growth, secretion , and regulation of membrane lipid synthesis in yeast. J. Biol. Chem., 273, 1998, 16635-16638.
Griac, P., Henry, SA. (1999).The yeast inositol-sensitive upstream activating sequence, UASINO, responds to nitrogen availability. Nucleic Acids Res., 27, 2043-2050
Valachovic, M., Hronska, L., Hapala, I. (2001). Anaerobiosis induces complex changes in sterol esterification pattern in the yeast Saccharomyces cerevisiae, FEMS Microbiology Letters 197, 41-45.