Lei Wang: Expanding the language of life

Organisms generally have only 20 amino acids to work with. True, they've managed to accomplish quite a bit with those ingredients, but imagine the possibilities if more choices were available. While a graduate student in Peter Schultz's lab at UC Berkeley, Lei Wang figured out a way to stick unnatural amino acids into E. coli proteins at rare stop codons. He did this by borrowing protein synthesis components, called orthogonal tRNA/aminoacyl syn-thetase-tRNA pairs, from other organisms such as the rugged archaebacteria (1). The resulting protein chi-meras have extraordinary properties. For example, Wang has made a growth hormone that sticks around longer than its natural counterpart and a mutant receptor that glows when meeting its formerly orphaned ligand. From 2002 to 2005, Wang worked as a postdoc with Roger Tsien (cowin-ner of the 2008 Nobel Prize in chemistry) at the Salk Institute. There, Wang attempted to hasten protein evolution by using somatic hypermutation—a process used by B cells to diversify immuno-globulins—to induce mutations in selected target genes. Using this strategy, Wang developed a new and improved red fluorescent protein with increased far-red emissions and photostability (2, 3), surpassing the best efforts of structure-based protein engineers. With high-throughput screening systems, this technology could generate a variety of therapeutically and industrially useful proteins. Think better detergents, both in the lab and at the laundromat. Since 2005, Wang has headed up his own lab at the Salk Institute, where he continues to push the envelope of protein evolution. He is also using unnatural amino acids to explore biological processes in mammalian cells and model organisms (4, 5). Where were you born, and did you know what you wanted to be when you grew up? I was born in southeast China. I think I always wanted to be a scientist. It's not because I knew that being a scientist would be exciting. It was simply because at that time, when I was young, every teacher told us in the classroom, " You want to be a scientist. " It's a strong message once you get it stuck in your mind. In the end, I was good at scientifi c courses, so I thought it would be a good idea to become a scientist. How did you begin working on unnatural amino acids? Pete Schultz had been putting unnatural amino acids into proteins in vitro for a long time. I think I joined the lab at …