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Pure Science

Lifting the lid off yeast

   
 
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What could be more ordinary than bread - yet baker's yeast is creating a stir among researchers. Because the structure of its genome, and probably at least a third of its genes, are similar to those of man.
A scientific first for Europe: the sequencing of the 6 000 yeast genes. 134 laboratories, working together in the EUROFAN project, are adding to our knowledge of this very special living organism, which has many genes comparable to those of humans. Their work, which has been characterised by a particularly innovative methodology, opens up highly promising prospects for the deciphering of genes of potential use in biomedicine and the bio-industry.

 

A complex living organism, with an elaborate genetic make-up, yeast has been used for thousands of years in everyday applications to make bread, beer and cheese, by artisans who used biotechnology without knowing it. Today, baker's yeast, Saccharomyces cerevisiae, is used widely in the synthesis of molecules on an industrial scale and has fascinated researchers for decades.

Indeed, the yeast cell shares numerous common features with the human cell. Its genome, divided into 16 chromosomes (but 250 times shorter than the human genome), was completely sequenced in 1996 thanks to the European Yeast Genome Sequencing Network (EYGSN) project, supported in large measure by the European Commission. After work lasting seven years, a network of European laboratories with links to American, Canadian and Japanese partners succeeded in sequencing 12.06 million bases, representing some 6 000 potential genes.

Of yeast and men
This collaborative scientific venture on a massive scale has produced some surprising results. For instance, the structure of the yeast genome, and probably at least a third of its genes, are similar to those of man. Some 50% of its proteins display a sequence of amino-acids indicating certain similarities to human proteins. Several dozen unknown genes, which could be involved in resistance to antibiotics and to drugs used in chemotherapy, owe their discovery to yeast. It is also known that certain yeast species are responsible for infections for which no satisfactory treatment exists. Accordingly, this vast mapping operation opens up very interesting prospects for the understanding of certain diseases - such as cancers and genetic diseases.

Deciphering the orphan genes
However, yeast did not yield up all its secrets in the course of the EYGSN project. Although the scientists succeeded in identifying certain genes known as "orphans", they were unable to discover their function. Nor were they able to link them to other known elements. How then could they be studied? By working backwards: instead of isolating a mutant cell in an attempt to identify the gene responsible for this effect, systematic steps would be taken to cause mutageneses - i.e. mutations of the targeted orphan genes - while at the same observing what function was affected as a result.

This "back-to-front" approach was adopted by the researchers involved in EUROFAN (European Functional Analysis Network) with the aim of capitalising on the potential opportunities offered by the sequencing of the yeast genome. Launched under the European Union's Biotechnology Programme, this ambitious project brought together 134 laboratories spread over 14 countries(1) in its initial phase (1994-1998). The first task facing the researchers was to select a thousand "orphan" genes and to attempt to analyse their function. This huge task was organised in a particularly efficient manner. Each team dealt with the mutagenesis of the genes assigned to it and, using codified methods, carried out an initial series of tests. During this stage an approximate function can be attributed to each gene, whereupon groups of related genes or genes that are involved in the same metabolic pathway can be routed towards the laboratory most qualified to analyse them further. More than 800 vectors, each incorporating a turned-off orphan gene, are used to study the latter's function. More than 350 of these genes have been isolated - i.e. cloned. The vectors and the isolated genes will be made available to the scientists and manufacturers by the European Centre for Genetic Archives (EUROSCARF).

High stakes, high outlay
"The scientific objectives of EUROFAN 1, i.e. the work on mutagenesis and the preliminary analysis, have been achieved. The coordination centres are operational, and the methods of analysis have been standardised. We can now move forward with optimism to EUROFAN 2, the second phase of the project, which is scheduled to last for two years," says Dr Stephen Oliver of the University of Manchester Institute of Science and Technology (UK), the scientific coordinator responsible for the project.

"Given the scale of the scientific effort, the magnitude of the financial outlay and the number of laboratories involved, it would be impossible to embark on a programme like EUROFAN without real political will," he goes on. "No country had the means to do so, and it has fallen to the European institutions to make possible the development of resources that will prove enormously useful to biomedicine and the bio-industry."

Equally ambitious, EUROFAN 2 (1998-2000), brings together 79 European laboratories.(2) Its aim: to analyse all the 6000 yeast genes. "A venture like this, on such a huge scale, demands flawless collaboration by the various participants, each of whom must maintain their position at the forefront of excellence and innovation," explains Bruno André, Director of the Physiology Laboratory of the Free University of Brussels, and involved in the project from the outset.

A network built round a
network It is now possible to look forward to a time when we will understand the functioning of a cell in its totality - a hitherto unprecedented achievement. Furthermore, this project has enabled us to establish a collaborative network of laboratories and has created the biological and informatics tools needed to speed up the study of much more complex organisms, such as plants and man himself.

The creators of EUROFAN have anticipated the development of even more ambitious projects and have evolved a structure to cope with this task. They have taken care to ensure that the work of the scientists will be backed up by consortia of services responsible for the administrative coordination and development of databases and other informatics tools designed to facilitate the use of the mass of data generated by the project itself. A centre for the storage of cultures and biological material needed for functional analysis purposes has been set up. In addition, the involvement of the YIP (Yeast Industrial Platform), a network of undertakings built up round the sequencing project, will guarantee the rapid transfer of technology to industry. At the industrial level, this innovative project is also producing spin-off benefits in terms of company and job creation. Thus it is that two German SMEs have come into being in the wake of the involvement of researchers in the original genome sequencing project.

(1) 27 laboratories in Germany, 21 in France, 10 in Switzerland, 9 in Belgium, 1 in Greece, 8 in Italy, 17 in Spain, 19 in the UK, 2 in Portugal, 2 in Sweden, 7 in Austria, 8 in the Netherlands, 1 in Denmark and 2 in Finland.
(2) 6 in Switzerland, 9 in Spain, 1 in Greece, 6 in Austria, 6 in Belgium, 12 in the UK, 14 in France, 11 in Germany, 4 in Italy, 6 in the Netherlands, 1 in Finland, 2 in Sweden and 1 in Portugal.


 

 

Project Title:  
European Network for the functional analysis of the yeast genes discovered by systematic DNA sequencing (Phases 1 and 2)

Programmes:
Biotechnology

Contract Reference: BIO4CT950080 BIO4CT972294

CORDIS databaseFor more information on this project,
go to the Cordis database Record 1-2

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