Biology Department Seminar

Tremendous advances have been made in reducing the cost of DNA synthesis. We are entering an age of synthetic biology, where we can design and synthesize new life forms for scientific and medical applications. Our group has designed weakened but viable strains of flu and poliovirus to serve as live vaccines. We have demonstrated that vaccination with our synthetic designs provides mice with effective protection against wildtype viruses, with a large margin of safety. Our gene design algorithms optimize the DNA sequence of a gene for particular desired properties while coding for a particular protein. For vaccine design, we optimize the codon-pair bias of a sequence to modulate expression. We have also developed sequence design algorithms to (1) optimize RNA secondary structure, (2) refactor genomes to add well-placed cloning/restriction sites, and (3) simultaneously encode two proteins in alternate reading frames. Finally, we have employed classical combinatorial objects like Gray codes, group testing, and de Bruijn sequences to propose new experimental approaches to biological signal location and transcription factor analysis. In this talk, I will discuss our experiences with designing and synthesizing these virus variants, review emerging technologies for large-scale synthesis, provide an overview of sequence design algorithms, and directions for future work.