ABI Innovation: Sequence Optimization for Synthetic Biology

Suny At Stony Brook, Stony Brook NY

Investigators

Abstract

A grant is awarded to Stony Brook University to generalize and expand computational approaches for designing gene sequences into a coherent set of tools for three areas of molecular biology: 1) sequence design for optimized gene expression; 2) signal identification and location; and 3) self-assembly. This project will improve our understanding of several sequence phenomena that occur in genomes, such as codon-pair bias, how RNA secondary structure and tRNA usage modulates gene expression, and how to use these results to develop gene design software to optimize gene expression. A new approach to identify the locations of critical DNA or RNA sequence signals (e.g. binding domains, secondary structures, and mRNAi targets) couples large-scale synthesis with sophisticated designs based on ideas from combinatorial group testing. This project will improve the efficiency and generality of this procedure, and will develop new homology-based software tools to identify candidate signals prior to employing combinatorial search approaches. New array-based oligo synthesis technologies provide access to tens or even hundreds of thousands of short custom sequences, but even greater power will become enabled if oligonucleotides can be designed to self-assemble into chromosome-sized sequences. Recombination systems in yeast provide the platform to conduct such experiments. This project will develop algorithms for the design of large-scale, self-assembling sequences, to best exploit new array-based synthesis technologies, and test how they work in practice. This collaboration between computational and life sciences researchers will advance both disciplines, through new results in combinatorial algorithm design and discrete optimization as well as fundamental discoveries regarding gene expression, signal detection, and self-assembly. Broader impacts of this project will result in software and experimental tools to advance broad areas of molecular biology, including the design of vaccines. Software and results of this project will be available from the website http://www.cs.stonybrook.edu/~skiena/dna.