Fungwall Partner 6

The fungal cell wall as a target for antifungal therapies

Partner 6

Departamento Microbiología y Genética /Instituto Microbiología Bioquímica
University of Salamanca /CSIC (Spain)

Principal scientist
Prof. C.R. Vázquez de Aldana

Other scientists
E. Duenas, Ch. Jimenez,
Dr F. del Rey, Dr C. Roncero

Universidad de Salamanca
Plaza Doctores de la Reina s/n
Salamanca - Spain

Experience of the participating organisation and scientists

Participating organisation

The proposed work will be carried out by two different research groups from the Fungal Morphogenesis Unit in the Instituto de Microbiología Bioquímica (Dept Microbiología y Genética). The Fungal Morphogenesis Unit, housed in the "Departmental Building" of the Faculty of Biology, is composed of 7 research groups focused mainly on the study of aspects of fungal morphogenesis and biogenesis of the fungal cell wall, including the analysis of enzymes involved in glucan and chitin biosynthesis, the characterization and study of cell wall remodelling enzymes and the regulation of cytoskeleton and morphogenesis by Rho proteins. The group of Dr C. Vázquez de Aldana and F. del Rey has worked on S. cerevisiae, S. pombe and C. albicans, focusing on the characterization of different families of proteins that are involved in the hydrolysis/transfer of glucan molecules. The second group, leaded by Dr. C. Roncero, has focused its research on understanding the structurefunction relationship of enzymes responsible of the chitin biosynthesis, as well as the regulatory proteins required to target the catalytic subunits to their membrane localization in S. cerevisiae and C. albicans. The University accommodates a range of central facilities, including those required for genomics analyses (transcriptomics, proteomics, mass spectrometry) and electron microscopy.

Participating scientists

Dr Vázquez de Aldana has worked for many years in the field of molecular genetics of S. cerevisiae and, more recently, S. pombe and C. albicans. His fields of expertise are hydrolytic enzymes, cell wall and gene expression. Prof. F. del Rey has more than 20 years of expertise in the field of Saccharomyces molecular genetics, cell wall remodelling enzymes and gene expression. The group of Dr Vázquez de Aldana and F. del Rey is focused on the study of yeast and fungal enzymes able to degrade alpha-glucans, either exo-alpha-1,3-glucanases and exo-alpha-1,3-glucanases. This group has also previous experience in large-scale projects, since they participated in the S. cerevisiae genome sequencing project and in the subsequent European Functional Analysis project (EUROFAN I and in the Cell Wall Node of EUROFAN II).

Prof. C. Roncero. is an expert on the analysis of chitin synthesis on S. cerevisiae and C. albicans. His work has been mainly dedicated to the characterization of chitin synthesis regulation in yeast models. Several genes required for the synthesis of bulk chitin in S. cerevisiae have been identified, including the mayor chitin synthase activity in vivo and several regulators of this activity. He has shown that regulation of chitin synthesis occurs through post-translational mechanisms that include intracellular sorting and activation of Chs3p. This work has also been extended to fungal pathogens (C. albicans and A. fumigatus). In addition, he is also studying the role of chitin synthesis as a part of the compensatory mechanism mediated by the cell integrity signalling pathway, uncovering the participation of the HOG and RIM pathways in cell wall assembly.
In addition, the two participant groups from the University of Salamanca are currently involved in the EUROCELLWALL project (EC, FW5 programme), aimed at the developing a series of high throughput screens to screen for antifungal drugs.

Relevant publications

Baladron, V., Ufano, S., Dueñas, E., Martin-Cuadrado, A.B., Rey, F. del, Vazquez de Aldana, C.R. (2002). Eng1p, an endo-1,3-alpha-glucanase localized at the daughter side of the septum, is required for cell separation in Saccharomyces cerevisiae. Eukaryotic Cell 1:774-789.

Ufano, S., San Segundo, P., Rey, F. del, Vázquez de Aldana, C.R. (1999) SWM1, a developmentally regulated gene, is required for spore wall assembly in Saccharomyces cerevisiae. Mol. Cell. Biol. 19:2118-2129.

Martín-Cuadrado, A.B., Dueñas, E., Sipiczki, M., Vazquez de Aldana, C.R., Rey, F. del. (2003) The endo-alpha-1,3-glucanase eng1p is required for dissolution of the primary septum during cell separation in Schizosaccharomyces pombe. J. Cell Sci. 116:1689-1698.

Sanz, M., Trilla, J.A., Duran, A. Roncero, C. (2002) Control of chitin synthesis through Shc1p, a functional homologue of Chs4p specifically induced during sporulation. Mol. Microbiol. 43:1183-1195.

Trilla, J.A., Duran, A., Roncero, C. (1999) Chs7p, a new protein involved in the control of protein export from the ER that is specifically engaged in the regulation of chitin synthesis in Saccharomyces cerevisiae. J. Cell Biol. 145:1153-1163.

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