Understanding the dynamics of translation regulation

Genome-scale knowledge of translational regulation has lagged behind that of transcription, despite a central role determining cell phenotype, and major implications for numerous diseases and cancer. The assay of choice for global gene expression profiling is RNA-seq, which makes sense for understanding transcriptional control. But levels of mRNA in a cell explain only a fraction of observed protein levels, and much of the remainder is due to translational control. Ribosome profiling (RP) or Ribo-seq is a novel genomic approach that delivers quantitative information on the number and behavior of ribosomes, and gives profiles of gene expression much more closely linked to actual protein levels. We are using Ribo-seq aligned with computational tools to identify alterations in translation regulation in cancer cells and study its behavior upon drug and radiation treatments. We are also interested in examining the role of aberrantly expressed ribosomal proteins in tumor development and determine if they affect translation in specific fashions.