Regulatory proteins control translation by scaling global protein production and by modulating translation from specific mRNAs. Targeted approaches continue to reveal new translation regulatory proteins, however there is currently no genome-wide functional genomics approach to identify translation control factors. Our laboratory will address this fundamental gap by devising an assay that quantifies translation activity (i.e. ratio of polypeptide synthesis to mRNA levels) of single cells and coupling this assay with genome-scale CRISPR based functional genomics.
We have recently developed a two-component system that can quantitatively and simultaneously measure ongoing polypeptide synthesis rate and poly-adenylated mRNA content of a single cell. Quantification of the ratio between polypeptide synthesis and poly-adenylated mRNA content can then be used to gauge the translation activity of single cells. Our laboratory will use this assay in conjunction with CRISPR-based functional genomic screens will to identify global regulators of translation. Broad application of this functional genomics assay and in-depth characterization of new translation regulatory factors will be a key focus of our laboratory.