Ingolia Lab

We study the translational control of gene expression in order to understand its molecular basis and its physiological function. Deep sequencing and RNA-Seq approaches are a major component of our research.

The translation of mRNA into protein is a central step in gene expression. Translational control plays a key role in diverse processes including cellular stress responses, developmental patterning, and synaptic plasticity. In my postdoctoral work, I developed a ribosome profiling technique that allows precise and quantitative measurements of genome-wide translation. It can be used to study translational control as well as to annotate the actual protein-coding sequences in complicated genomes and transcriptomes.

Ribosome profiling also revealed extensive translation upstream of many genes. This unexpected translation points to the regulated use of alternate sites of initiation, including substantial initiation at non-AUG codons. We believe that start codon selection is an underappreciated point of control in gene expression. The use of alternate sites of initiation can produce functionally distinct protein isoforms as well as affect the amount of protein synthesized. This poses several questions that we want to address.

• What genes show regulated changes in translation during normal physiological processes or during stress?
• How does the translation initiation apparatus change its start site preferences in different circumstances?
• How does the sequence of the transcript contribute to initiation site selection, and in particular how do different start sites affect each other?