Trends in Pharmacological Sciences
Yeast as a model for medical and medicinal research
Section snippets
Yeast: a model for fundamental and applied research
The unicellular bakers' yeast Saccharomyces cerevisiae is a proven model eukaryote for molecular and cellular biology studies. Yeast growth and division can be controlled efficiently and effectively by adjusting environmental conditions. Yeast is also genetically well defined: its entire genome sequence has been elucidated and the corresponding databases are generally accessible (Table 1). Moreover, it is a genetically tractable organism, amenable to modifications such as gene disruption, gene
Yeast genes and human disease
Comparison of the yeast and human genomes, reported in 1997, revealed that 30% of known genes involved in human disease have yeast orthologs (i.e. functional homologs) [3]. Furthermore, hundreds of yeast genes exhibit a link to human disease genes (Table 1). Most of these genes correspond to key components in signal transduction or specific metabolic processes. Although it is sometimes difficult to assess the functional conservation between yeast genes and human disease-associated genes, yeast
Advances in yeast technology
The yeast genome was the first published eukaryotic genome sequence [5]. Since the publication of this sequence in 1996, a wealth of genome-wide information has become available (Table 1) as a result of a collective effort in functional analyses. Indeed, Saccharomyces cerevisiae has emerged as one of the eukaryotic model systems of choice for the development of genomic technology [6]. The field of yeast genomics, among others, encompasses genome-wide mutational analyses to investigate the
Protein–protein interactions
Yeast cells represent a ‘toolbox’ for protein–protein interaction studies. A widely applied tool is the two-hybrid analysis and its variants, the one-hybrid or three-hybrid screens. By applying two-hybrid analyses in yeast, it has become possible to search for molecular partners of a large number of eukaryotic (including human) proteins of interest. The three-hybrid approach has been used, for example, to scan the proteome for targets of kinase inhibitors [14]. The techniques are outlined in
Yeast cell-based assays and humanized yeasts
Yeast transformants bearing a human cDNA that functionally complements a yeast mutation are the ‘classic’ cell-based systems that have been created for medicinal purposes (Table 2). In these cases the phenotype of a yeast mutant can be ‘rescued’ by the expression of a human protein. This finding can form a starting point for more-detailed structure–function studies in yeast, and might also lead to the identification of novel effector molecules. For example, p53, a key regulator of cell cycle
Concluding remarks
Yeast research performed in the recent past has demonstrated the tremendous potential of this organism as a model system for medical and medicinal purposes. Fundamental studies in yeast have made a considerable contribution to our present understanding of conserved biological processes. In addition, yeast has proven to be a valuable experimental tool, in particular in the development of genomic technologies. Genome-wide approaches have provided a wealth of information about the function of
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