Optimizing the Design of Coding Sequences

URL: http://www.efgenomics.org/

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. But what sequence properties optimize translation and gene expression? Our gene design algorithms optimize the DNA sequence of a gene for particular desired properties while coding for a specified protein. For vaccine design, we optimized the codon-pair bias of a sequence to modulate expression. We have also developed sequence design algorithms to optimize the presence of RNA secondary structure and the degree of sequence autocorrelation, which effects the frequency of tRNA reuse and recycling. In this talk, I will discuss our experiences with designing and synthesizing these coding sequences, and their resulting phenotypes. I will also present some recent work analyzing ribosome profiling data to understand the impact of codon-bias on translation efficiency. (joint work with Justin Gardin, Ruhksana Yeasmin, Alisa Yurovsky, and Bruce Futcher)