Research in this section is focused on understanding translational regulatory mechanisms and the molecular details of protein synthesis in eukaryotic cells. Given its critical importance as the ultimate step in gene expression and its significant energy requirements, the fidelity and efficiency of protein synthesis are key elements for cell growth and development. Moreover, regulation of protein synthesis is an important element in the innate immune response against pathogens. The initiation phase of eukaryotic protein synthesis requires the activity of at least 12 trans-acting proteins referred to as translation initiation factors (eIFs) and translation elongation is assisted by two well-conserved eukaryotic elongation factors (eEFs). We are using molecular genetic, biochemical and structural analyses to more fully elucidate the roles and structure/function properties of translation factors. We also investigate stress-responsive protein kinases that phosphorylate the initiation factor eIF2α, viral regulators of these kinases, and how cellular phosphatases are targeted to dephosphorylate eIF2α. We are characterizing mutations in eIF2γ that are associated with MEHMO syndrome, a novel X-linked intellectual disability, we are investigating the function of the translation factor eIF5A, the role of its hypusine modification, and the role of this factor in gene-specific translational control mechanisms, and we are characterizing metabolite control of translation via upstream Conserved Coding regions in select mRNAs.