Protein synthesis and its regulation are essential for gene regulation. For all organisms, protein synthesis takes place in the ribosome, a remarkable molecular machine in all cells. Protein synthesis is mainly regulated at the initiation and the termination stages where the ribosome is complexed with cellular regulatory and translational protein factors to function. Translation directly influences important cellular processes such as development, differentiation, growth, cell fitness and cellular adaptive responses to the external environment. Consequently, regulatory dysfunction in translation results in numerous diverse human diseases including metabolic disorders, neuronal degenerative diseases and cancer. We are pursuing the molecular understanding of translation and its regulation using biochemical, genomic, and biophysical methods with an emphasis on macromolecule crystallography.