Protein synthesis, or mRNA translation, is a highly energy-consuming cellular process. To adjust the rate of protein synthesis to physiological changes (e.g. cell growth and differentiation) and stress (e.g. energy/nutrient deprivation and infection), cells have evolved sophisticated regulatory mechanisms, collectively called, “Translational Control.” Translational control has been documented primarily at the initiation step when ribosomes are recruited to mRNA through the collaborative action of several proteins known as eukaryotic translation initiation factors (eIFs). Important signaling pathways, including mTOR, MAPK and ISR, control translation initiation through phosphorylation of eIFs.
We utilize a variety of high throughput, in vitro and in vivo systems to investigate fundamental unresolved questions regarding how translational control regulates gene expression and how it contributes to stem cell function and human disease. Many groups have focused on the role of transcriptional control in different biological systems. However, the mRNA translational control also plays an important role in gene expression and its functional significance in determining the cellular proteome is not well understood. To this end, we have been employing state-of-the-art high throughput (e.g. ribosome profiling), animal model and synthetic biology (e.g. iPSC and CRISPR) approaches to investigate which mRNAs are being translationally upregulated or repressed in physiological/pathological conditions.