Gene-Wei Li seeks to understand how cells achieve precise levels of gene expression. An astonishing aspect about the flow of genetic information is the transformation from individual genes in a genome into vastly different, and yet specific, levels of proteins. This quantitative transformation is what enables a genome to become a competitive life-form. Yet we cannot derive the levels of protein synthesis – even qualitatively – from genomic sequences. Solving this problem will transform our ability to utilize powerful DNA sequencing to predict mutational consequences, as well as leveraging DNA editing to robustly engineer cellular functions.