Increasing evidence indicates that eukaryotic cells make use of specific nutrient signalling pathways for control of growth and growth-related properties. In the yeast Saccharomyces cerevisiae, the protein kinase Sch9 plays an important role in nutrient-induced signal transduction and growth control, but the precise mechanisms involved are not well understood. Sequence similarity suggests that protein kinase Sch9 represents the yeast homologue of mammalian protein kinase B (PKB). A role of Sch9 in nutri ent-induced signalling is indicated by the observation that deletion of the SCH9 gene deregulates fermentable growth medium (FGM) signalling. The fermentable growth medium (FGM)-induced pathway maintains activation of protein kinase A targets during gro wth on a fermentable carbon source like glucose. In this project several approaches will be taken to identify new components of the Sch9 nutrient signalling pathway. First, downstream components of Sch9 will be identified as multi-copy suppressor genes o f the growth defect caused by deletion of Sch9 in a specific genetic background. Second, upstream activators of Sch9 will be identified by transposen mutagenesis using a specific genetic background in which inactivation of the upstream components is leth al and can be rescued by induction of Sch9 overexpression. The relationship between the new components identified and other components closely connected to Sch9, such as PKA, Rim15, Yak1 and the two Pkh proteins will be established using epistasis analy sis. Execution of this project will allow advanced training in yeast molecular genetics, recombinant-DNA technology, bioinformatics and determination of a variety of biochemical parameters. In addition, the applicant will be able to develop her skills in research supervision and her potential for independent scientific research.
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