Fungwall Partner 3

The fungal cell wall as a target for antifungal therapies

Partner 3

Swammerdam Institute For Life Sciences, University of Amsterdam (The Netherlands)

Principal scientist
Dr Frans M. Klis

Other scientists
Prof. K. Hellingwerf, Prof. C. de Koster, Dr L. De Jong, Prof. S. Brul

Nieuwe Achtergracht 166
Amsterdam 1012WX Netherlands
+31-20-5257834 - +31-20-5257055
Fax 31-20-5257056

Experience of the participating organisation and scientists

Participating organization

The Swammerdam Institute for Life Sciences (SILS) is part of the Faculty of Science of the University of Amsterdam and has a staff of 230. The proposed work will be carried out in SILS by the Molecular Microbial Physiology Group (Prof. Hellingwerf, Dr F. Klis) and the Mass Spectrometry of Biomacromolecules Group (Prof. De Koster, Dr De Jong). The Microbiology Group of Prof. Hellingwerf has extensive expertise in microbial physiology, signal transduction proteins, and transcriptome analyses. The Mass Spectrometry Group studies the functional organization and dynamics of biological macromolecular complexes as part of a larger framework of functional genomics and systems biology. Various mass spectrometric techniques are operational, including MALDI-TOF, LC/MS/MS, and SELDI-TOF for protein identification on ProteinChip surfaces. A new hybrid Q-FTICR mass spectrometer is being installed, combining data-dependent ion acquisition and high mass accuracy. SILS further accommodates a number of well-equipped central facilities such as the Molecular Cytology Group for CSLM, the Microarray Division, and a Bioinformatics Group.

Participating scientists

Dr Klis will be principal investigator for FungWall within the Swammerdam Institute for Life Sciences (SILS). He has worked on the molecular organization and construction of yeast cell walls for 16 years and has lately focused on functional and transcriptional analysis of cell wall-related genes and on the regulatory mechanisms that control and coordinate their activities, in particular under conditions of cell wall stress. He has over 70 publications in this field. He has coordinated the Cell Wall node in EUROFAN II and has participated in GALAR FUNGAIL, which has annotated the Candida albicans genome and in collaboration with EUROGENTEC has produced the first micro-arrays for this organism. Dr Klis has a longstanding collaboration with Prof. Brul from Unilever for applying the results of his research in the Food Processing Industry. His group receives and has received financial support from various industries, including GLAXO, AVENTIS, UNILEVER and DSM. Recent results of his group include a molecular description of the cell wall of S. cerevisiae and C. albicans and the development of a genomic algorithm for the identification of GPI-dependent cell surface proteins in fungi. Dr De Jong of the Mass Spectrometry Group is an expert on the development and application of mass spectrometric techniques for structural and functional analysis of proteins and proteomes. In collaboration with Dr Klis, methods are being developed for a quantitative analysis of the cell wall proteome in S. cerevisiae and C. albicans and for monitoring the dynamics of the cell wall proteome in response to changes in environmental conditions. In addition, methods will be developed for monitoring the dynamics of plasma membrane-bound cell wall construction enzymes (this project).

Relevant publications

De Groot, P.W., Hellingwerf, K.J. Klis F.M. (2003) Genome-wide identification of fungal GPI proteins. Yeast. 20:781-796.

Klis, F.M., Mol, P, Hellingwerf, K., Brul, S. (2002) Dynamics of cell wall structure in Saccharomyces cerevisiae. FEMS Microbiol. Rev. 26:239-256.

Hochstenbach, F., Klis, F.M., van den Ende, H., van Donselaar, E., Peters P.J., Klausner, R.D. (1998) Identification of a putative alpha-glucan synthase essential for cell wall construction and morphogenesis in fission yeast. Proc. Natl. Acad. Sci. USA. 95:9161-9166.

Back, J.W., de Jong, L., Muijsers, A.O., de Koster, C.G. (2003) Chemical cross-linking and mass spectrometry for protein structural modeling. J. Mol. Biol. 331:303-313.

Back, J.W., Sanz, M.A., De Jong, L., De Koning, L.J., Nijtmans, L.G., De Koster, C.G., Grivell, L.A., Van Der Spek, H., Muijsers, A.O. (2002) A structure for the yeast prohibitin complex: Structure prediction and evidence from chemical crosslinking and mass spectrometry. Protein Sci. 11:2471-2478.

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