I will use novel genome-wide approaches to investigate the transcriptional basis of the non-genetic heterogeneity driving divergent gene expression responses within a clonal population using S. cerevisiae. This research has a dual objective: 1) to refine our knowledge of translation regulation and its contribution to cell-to-cell variability, and 2) to develop novel genome-wide approaches to functionally characterize and assign molecular and cellular phenotypes to subtle variations of the transcriptome. These approaches will be complemented by analysing the molecular phenotypes of the mRNA isoforms (e.g., association to ribosomes or RNA binding proteins). This will allow linkage of molecular phenotypes with cellular consequences, and highlight those variations with higher functional potential. Once I identify novel mechanisms implicated in the appearance of phenotypically divergent cells, I will characterize selected targets using biochemical and molecular biology tools.