Chemotyping of yeast mutants using robotics

By now, the EUROFAN programme for the functional analysis of genes from the yeast genome has attained its cruising speed. Indeed, several hundreds of yeast mutants with no phenotype as tested by growth on standard media and n o significant sequence similarity to proteins of known function are availab le through the efforts of various laboratories. Based on the methodology in itiated during the pilot project on yeast chromosome III (Yeast 13, 1547-15 62, 1997) we adapted it to High Throughput Screening (HTS), using robotics. The first 100 different gene deletions from EUROSCARF, constructed in an F Y1679 strain background, were run against a collection of about 300 inhibit ors. Many of these inhibitors have not been reported until now to interfere in vivo with growth of Saccharomyces cerevisiae. In the present paper we p rovide a list of novel growth conditions and a compilation of 49 yeast dele tants (from chromosomes II, IV, VII, X, XIV, XV) corresponding to 58% of th e analysed genes, with at least one clear and stringent phenotype. The majo rity of these deletants are sensitive to one or two compounds (monotropic p henotype) while a distinct subclass of deletants displays a hyper-pleiotrop ic phenotype with sensitivities to a dozen or more compounds. Therefore, ch emotyping of unknown genes with a large spectrum of drugs opens new vistas for a more in-depth functional analysis and a more precise definition of mo lecular targets. Copyright (C) 1999 John Wiley & Sons, Ltd.