Welcome to the Lapointe lab website! We are driven by questions that underlie how human messenger RNAs (mRNAs) and the ribosome are regulated to determine when, where, and how much of a protein to synthesize. Dysregulated protein synthesis is a universal feature of cancer and a hallmark of viral infections. Yet, molecular models for how translation is controlled remain poorly defined. We therefore examine the interplay between the mRNA, the translation initiation machinery, and the vast repertoire of human and viral proteins that define the efficiency of protein synthesis in space and time. The fundamental discoveries uncovered by our research group will enhance understanding of how cells function and reveal how control goes awry in human diseases, such as cancers and viral infections.

To overcome long-standing challenges, we use a multidisciplinary strategy: we integrate single-molecule spectroscopy and structural approaches using purified components with high-throughput functional assays in vitro and in cells. Single-molecule fluorescence assays monitor processes as they unfold in real time with sub-second time resolution. The approach delineates parallel pathways, defines molecular timing, and reveals elusive checkpoints. Such analyses also pinpoint transient intermediates to analyze using structural techniques, thereby illuminating key conformational insights. The strong foundation provided by our in vitro research enables us to develop and test hypotheses using advanced transcriptome-wide and high-throughput approaches.

Control of translation by human regulatory proteins

Cellular mRNAs are coated in proteins. The bound proteins control all aspects of mRNA function. Such control, particularly at the key step of translation initiation, is a pillar of cellular function. Its dysregulation is implicated broadly in cancers, neurological and developmental disorders, and infections. We therefore focus on two outstanding questions. First, how is the efficiency of translation initiation defined by macromolecular regulatory complexes bound throughout an mRNA? Second, how do multiple regulatory complexes compete and coordinate with one another to define mRNA translation efficiency, stability, and localization? We address these questions by examining vital regulatory complexes and the RNA-binding proteins that target the complexes to particular mRNAs using our multidisciplinary strategy.