Yeast as a model for medical and medicinal research

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In the past, studies using the yeast Saccharomyces cerevisiae enabled major breakthroughs in the understanding of basic cellular and molecular processes. Today, the use of yeast is undergoing a ‘rebirth’ in both fundamental and applied research. Indeed, advances in yeast technology have paved the way for a variety of new genome-wide screening approaches. Experimental strategies using yeast aim to unravel disease-related molecular events and to discover novel medicinal compounds. In this article, the impact of yeast as an experimental tool for disease-related studies is summarized and the use of yeast in high-throughput screenings for pharmacological purposes is evaluated. The recently applied and promising approach of so-called humanized yeast systems is also discussed.

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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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