Chris Voigt: Biology's toy maker

© Cody Pickens

In May, two years after Chris Voigt moved into his new lab at the University of California, San Francisco, his light-colored wood desks and cabinets still smell like sawdust - just as you'd imagine a traditional toy maker's shop to smell. Voigt doesn't build toys out of wood, however; he builds them out of biological parts.

Having trained in chemical engineering, Voigt never intended to become a biologist. As an undergrad at the University of Michigan, Voigt was first introduced to protein biology through a chance encounter with Richard Goldstein, who was looking for someone with training in higher-order mathematics and statistics to work in his lab. Voigt was the perfect choice. While he became interested in the question of protein evolution, the engineer in Voigt wanted to manipulate what he was observing.

In graduate school, at Caltech, he pooled the expertise of three advisors - Zhen-Gang Wang, Francis Arnold, and Steven Mayo - to help him direct the evolution of subtilisin E and T4 lysozyme. Voigt developed a computational tool ¹ to find areas of the gene where mutations are most likely to lead to more desirable proteins, such as enzymes that could turn cellulose into biofuel. Instead of mutating an entire gene to identify superior proteins, Voigt's program worked by targeting particular areas in the gene of interest that would benefit from directed mutation.

Wang remembers that Voigt really powered the project. "We were just giving him some side advice." Voigt also designed an algorithm that would manipulate amino acid sequence without altering a protein's structure, by calculating the number of amino acid residues that interact in a protein, and determining how many of those interactions are broken with each hybrid protein. ² In 2002 Voigt finished his four-year PhD program and became the most sought-after candidate in chemical engineering in the country that year, says Wang.

Already having secured an assistant professorship at UCSF, Voigt went on to do a one-year postdoc with Adam Arkin at UC, Berkeley. "I wanted to expand from studying the evolution of individual protein/enzymes to understanding the evolution of networks," Voigt says. Borrowing parts from other species, they engineered Escherichia coli that could traffic to and invade cancer cells, with the ability to potentially deliver a cytotoxic payload.

In 2003, when Voigt went on to start his own lab at UCSF, he was eager to get creative. His first "toy system," as synthetic biologists call it, was a lawn of E. coli that reacted like a strip of film - turning white where light was shone, and black where it wasn't. ³ For one of his next toys, Voigt is making a strain of Salmonella that can make and spin its own spider silk, a substance as strong as Kevlar (the material used to make bullet-proof vests) but ten times more elastic. Says Arkin, "He's unafraid of trying new things that might seem crazy."