We study the mechanism and regulation of protein synthesis, focusing on GTPases, protein kinases, translation factors, and mRNA features that control this fundamental cellular process. We use molecular-genetic and biochemical studies in yeast and human cells to dissect the structure-function properties of translation factors, elucidate mechanisms that control protein synthesis, and characterize how mutations in the protein-synthesis apparatus cause human disease. Of special interest are translation initiation factors eIF2 (eukaryotic initiation factor 2), a GTPase that binds the initiator methionyl-tRNA to the ribosome, and eIF5B, a GTPase that promotes ribosomal subunit joining. Using yeast, human cells, and mouse models, we are characterizing mutations in the eIF2gamma protein that are associated with MEHMO syndrome, a rare X-linked intellectual disability syndrome associated with dysregulation of the Integrated Stress Response (ISR). We are also studying the translation factor eIF5A, a protein that stimulates the peptidyl transferase activity of the ribosome and is especially important to facilitate the reactivity of poor substrates such as proline. We are examining the role of the unusual hypusine modification on eIF5A, diseases caused by mutations in the hypusine modification enzymes, and the role that eIF5A plays in polyamine-regulated translational control mechanisms. Finally, we are characterizing the fungal polyamine transporter Hol1 and metabolite control of translation via non-canonical upstream open reading frames (uORFs) in select mRNAs.

For more information on the Section on Protein Biosynthesis, see the Personnel page or read the bio page for Dr. Thomas Dever.