The goal of this project is to develop nano-biotechnologies in order to exploit information obtained from global gene expression studies. The programme will be built on the use of reliable, cheap and re-usable micro/macroarrays for high throughput, low-costs screenings. S. cerevisiae, the only eukaryote for which the complete genome sequence is available and the functions of the genes are being rapidly elucidated will be used to characterise, in detail, regulatory networks on a genome-wide scale. Drawing the integrated genetic and metabolic map of this simple eukaryote will allow biotechnological improvments of many bioprocesses, access to key target genes homolog to human genes involved in diseases and systematic screening of new drugs and fungicides.
The Project focuses on the technological development of reasonably priced, reusable, and reproducible hybridisation arrays. We will exploit the enormous potential of the yeast system to characterise the proteins which control its transcriptome and, consequently, its metabolome in order to produce a genetic and metabolic map of this basic eukaryotic cell. The detailed characterisation of regulatory networks on a genome-wide scale will enable the establishment of high throughput, low-cost methods for the screening and validation of new drugs for either medical or veterinary use as well as novel fungicides for plant protection.
DESCRIPTION OF THE WORK
The tasks are grouped into six work-packages that, in an integrated and synergistic way, will permit the validation of S. cerevisiae for the identification of new medical and veterinary drugs, as well as novel fungicides.
- Work-package 1 will focus on the technological development of micro/macro-arrays that are sufficiently cheap and reliable for use in industrial screens.
- Work-packages 2 to 5 represent an integrated programme for studying global controls on gene expression. Work-package 2 will study, at the level of both the transcriptome and metabolome, the effects of modification of transcriptional activators on key metabolic pathways. Based on this genomic technology, new ways to modulate biomass or the production of primary and secondary metabolites will be found.
- Workpackage 3 will identify and characterise transactivators involved in the control of cell growth and division. Given that basic regulatory mechanisms are conserved between yeast and humans, the elucidation of these pathways should identify key genes whose products could be useful therapeutic targets.
- Work-package 4 is devoted to studying transactivators of unknown function in order to maximise the chances of identifying novel therapeutic or fungicidal targets.
- Workpackge 5 will focus on the effects of accessory proteins that act as co-activators/repressors of transcription factors and which could be sensitive targets for drug or fungicide action.
- Workpackage 6 will establish basic protocols for drug-screening in yeast for validation and further exploitation of yeast as a model system.
- Technological development of robust micro/macroarrays for monitoring the yeast transcriptome in a reproducible and economic way.
- Identification of transactivators for exploitation in remodelling metabolic pathways to optimise the production of biomass or specific metabolites.
- Elucidation of the effects of yeast transactivators homologous to human proteins involved in diseases.
- Definition of new transactivation pathways.
- Identification of accessory proteins that could be drug targets.
- Establishment of standard protocols and validation of yeast for industrial drug screening.
Dr. Monique Bolotin-Fukuhara
Laboratoire de Génétique Moléculaire
Institut de Génétique et Microbiologie
Batiment 400. Université Paris-Sud
91405 Orsay Cedex, France
Tel: +33 169156201/4622
Fax: +33 169154626
Prof. B. Dujon
28 Rue du Dr. Roux
75274 Paris, France
Tel: +33 145688478
Fax: +33 140613456
Rue du Bois Saint Jean, 14
4102 Seraing, Belgium
Tel: +32 43660150
Fax: +32 43651604
Dr. Alain Fournier
Core Biotechnoloy/Yeast Genomics
13 Quai Jules Guesde
94403 Vitry sur Seine, France
Tel: +33 155713740
Fax: +33 155713070
Prof. Antony Wright
Section for Natural Sciences
Alfred Nobel's Allé 10
141 04 Huddingue, Sweden
Tel: +46 858588708
Fax: +46 858588510
Prof. Enrique Herrero
Facultat de Medicina
Universitat de Lleida
Dept. de Ciencies Mediques Basiques
Rovira Roure 44
25198 Lleida, Spain
Tel: +34 973702409
Fax: +34 973702426
Prof. Stephen Oliver
Victoria University of Manchester
School of Biologial Sciences
Stopford Building, Oxford Road
M13 9PT Manchester, United Kingdom
Tel: +44 1616067260
Fax: +44 1616067306
Prof. Jens Nielsen
Technical University of Denmark
Department of Biotechnology
Centre for Process Biotechnology
Anker Engelundsvej, Building 223
2800 Lyngby, Denmark
Tel: +45 45252696
Fax: +45 45884148
Prof. E. Dubois and F. Messenguy
Department of Molecular Biology and Institute of Microbiological Research J.M.Wiame (IRMW)
Avenue Emile Gryzon, 1
1070 Brussels, Belgium
Tel: +32 25267277
Fax: +32 25267273
Dr. Roland Beffa
La Dargoire Research centre
PO Box 9613
14/20 Rue Pierre Baizet
69263 Lyon, France
Tel: +33 472852935
Fax: +33 472852297