We seek to discover how cells control the expression of genes during translation by the ribosome. We’re interested in both the mechanisms that underlie basic steps in translation, such as termination and recycling, and how these processes are regulated to carry out cellular function.
We employ high-throughput tools such as ribosome profiling, biochemical techniques, and computational methods to study translational control of gene expression in yeast and mammalian cultured cells. We’re also developing single-molecule fluorescence approaches to address mechanistic questions about ribosome function in cells and in vitro.
We recently discovered that failure of the ribosome recycling factor ABCE1/Rli1 to properly remove ribosomes from mRNAs at stop codons leads to reinitiation of new translation in 3’UTRs and production of short peptides. We’re now investigating the mechanism of this non-canonical process and potential functions for the peptide products in helping cells adapt to stress, such as nutrient starvation, and defend against viral infection. We’re also interested in the “rescue” process that takes place when ribosomes arrest after translation of particular sequences, such as the poly(A) tail of prematurely polyadenylated mRNAs.
We’re also pursuing general questions of how translation is coupled to mRNA decay and protein localization.