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The fungal cell wall as a target for antifungal therapies

Partner 2

University of Aberdeen (UK)
School of Medical Sciences, Institute of Medical Sciences

Principal scientist
Prof. Neil A.R. Gow

Other scientists
Dr Carol Munro, Dr Sarah Milne,
Prof. Frank Odds, Prof. Alistair Brown

IMS Building, AB25 2ZD Aberdeen, UK
+44-1224-555879 - +44-1224-555871
fax +44-1224-555844

 

Experience of the participating organisation and scientists

Participating organisation

Professor Gow and partners are part of the Aberdeen Fungal Group (AFG), which is the largest centre for medical mycology in the UK and one of the largest world-wide, comprising some 50 research scientists. They are housed in new state-of-the art facilities within the new Institute of Medical Sciences. Professor Gow is the leader of the Microbiology research theme that links all microbiological research in the faculty of Medicine. His group is known for his work in a range of areas including the analysis of chitin synthesis and glycosylation of cell wall proteins, the regulation of yeast hypha morphogenesis and hyphal tropisms. The AFG has expertise in aspects of medical mycology from studies of gene expression and the development of molecular tools for C. albicans through to studies of virulence and antifungal drug action. The group has developed and refined methodologies for gene disruption, reporter gene analysis, vectors for gene analysis and other technologies for the systematic analysis of C. albicans. The AFG is the centre of COGEME - a functional analysis facility for fungi in which Professor Brown runs the associated proteomics facility for the UK. Modern faculties for array technologies, confocal and other imaging technologies, virulence testing and drug sensitivity analysis are available on site.

Participating scientists

Professor Gow has 24 years experience working on fungal pathogens and cell wall biosynthesis. He was a member of an EC FP5 consortium on fungal walls (EUROCELLWALL; Project QKL3-2000- 01537) -"Exploiting yeast cell wall for high throughput screening of antimicrobial agents". The Aberdeen Fungal Group which he has directed has some 40 scientists working on clinically relevant fungi and has access to significant facilities for research in medical mycology. Colleagues in this group include Professors Frank Odds, an expert in medical mycology with 10 years experience as head of antifungal drug discovery at Janssen Pharmaceuticals and Alistair Brown, an expert fungal molecular biologist working on gene regulation in Candida. Professor Gow's recent work has focussed on chitin synthesis, glycosylation and morphogenesis in Candida albicans. He is currently President of the British Mycological Society and Chairman of the Infection and Immunity Panel of the Wellcome Trust. Professor Gow will focus on the analysis of chitin synthesis examining its regulation at the transcriptional level and defining key interacting proteins and developing screens for novel inhibitors. His project will involve collaboration with partners 1, 6, and 9 and with Dr Carol A. Munro at Aberdeen (a Candida molecular biologist in his group with specific expertise in chitin synthesis).

Relevant publications

Buurman, E., Westwater, C., Hube, B., Odds, F.C., Brown, A.P.J, Gow, N.A.R. (1998) Molecular analysis of CaMnt1p, a mannosyl transferase important for adhesion and virulence of Candida albicans. Proc. Natl. Acad. Sci. USA 95:7670-7675.

Thomson, L.M., Yamazaki, S., Arisawa, M., Aoki, Y., Bates, S., a Gow, N.A.R. (2000) Functional characterization of the Candida albicans MNT1 mannosyltransferase expressed heterologously in Pichia pastoris. J. Biol. Chem., 275:18933-18938.

Munro, C.A., Winter. K., Buchan, A.D.B, Becker, J.M., Brown, A.J.P, Bulawa, C.E., Gow, N.A.R. (2001) Chs1 of Candida albicans is an essential chitin synthase required for synthesis of the septum and for cell integrity. Mol. Microbiol. 39:1414-1426.

Munro, C.A., Whitton, R., Hughes, B., Reilla, M., Selvaggini S. & Gow, N.A.R. (2003). CHS8 a fourth chitin synthase gene of Candida albicans contributes to in vitro chitin synthase activity, but is dispensable for growth in vivo. Fung. Gen. Biol., 40:146-158.

Hobson, R.P. Munro, C.A., Bates, S., MacCallum, D.M., Cutler, J.E., Heinsbroek, S., Brown, G.D., Odds, F.C. , Gow, N.A.R. (2004). Loss of cell wall phosphomannan in Candida albicans does not influence macrophage phagocytosis and function. J. Biol. Chem., 279:39628-39635.

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