Research Interests

My work is focused on deciphering the molecular mechanisms that are at the heart of protein synthesis in all organisms. By focusing on these questions, we are able to ponder the early evolutionary steps that led to life on earth from a more primitive RNA world, but in a system where biological questions drive the experiments. Since my arrival at Hopkins, we initially focused on using pre-steady state kinetic approaches to define key molecular features in the ribosome responsible for the decoding and peptidyl transferase steps of elongation. These approaches led to the identification of a novel post-peptidyl transfer editing step on the bacterial ribosome that is important in maintaining the high fidelity of translation. More recently, the group has been focused on mRNA surveillance pathways in eukaryotes, and in particular, how this process is driven by ribosome-based recognition of mRNA 'quality'. For these experiments, the laboratory uses both an in vitro reconstituted yeast translation system, in vivo-based reporters, and finally, ribosome profiling. This combined set of approaches allows us to define key biochemical reactions in a test tube, and then to ask what role these mechanisms play in determining the gene expression output of the organism.

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Section 21: Biochemistry