Systematic and functional genomics of coding and non-coding transcription during gene expression regulation in yeast

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Cellular protein homeostasis ensures that the optimal amount of each protein is available at its site of action within an organism. This homeostasis is monitored by a series of regulatory systems - from control of gene expression and mRNA translation to protein removal via degradation pathways. Together they ensure the ideal amount of each protein in any given situation. It has become evident that the classical model of promoter-mediated gene regulation alone cannot fully explain gene expression. Rather, a number of other factors, such as transcription of overlapping non-coding RNAs, chromatin structure and genomic location, also play important roles in gene regulation. The aim of this project is to investigate the regulation of single genes comprehensively in order to quantify the contribution of each of these factors. To reach this goal, we will apply two complementary methods based on high-throughput genetics and CRISPR/Cas9 mediated genome editing. We will use baker's yeast as a model organism to explore a large number of genes, coding sequences and non-coding transcripts in the context of cellular fitness. The project will be carried out within a well-established collaboration between a genome biology / bioinformatics oriented work group at EMBL and a cell biology group at the ZMBH. The experiments we will perform aim at exploring the basic principles of gene regulation using quantitative methods.