Our group studies the process of mRNA translation by which proteins are produced in all living cells. Our long-term goals are to dissect the molecular mechanisms and systems-level regulatory principles of translation, and to decipher their functional consequences for cellular physiology and disease. Towards these goals, we use an integrated approach combining high throughput experiments in human cells with computational modeling. In previous studies, we uncovered a role for ribosome collisions in co-translational quality control, identified cis-regulatory motifs in protein coding regions that shape mRNA stability, and dissected non-canonical translation events during viral infection that shape viral proteomes and host immune responses.
Our current research is focused along three directions: First, we are identifying and dissecting the gene networks that regulate mRNA translation in a sub-cellular and environment-specific manner. This work uses an RNA-linked CRISPR platform that we recently developed to study the genetic control of RNA metabolic phenotypes in human cells. Second, we are formulating computational approaches to simulate and visualize biochemically accurate models of post-transcriptional gene regulation, and test them against high-throughput experimental data. Third, we are using massively parallel screens to study immune-modulatory peptides that are generated by non-canonical translation events.