Research in this section is focused on understanding translational regulatory mechanisms and the molecular details of the initiation 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). We are using molecular genetic, biochemical and structural analyses to more fully elucidate the roles and structure/function properties of the translation initiation factors and a family of stress-responsive protein kinases that phosphorylate the factor eIF2.