Synthetic Biology moves beyond conventional genetic manipulation to construct novel biological components which do not originate in nature. There still exists though a big gap of knowledge between genomic sequence and function. To enhance understanding of gene expression, researchers have constructed and evaluated libraries of gene variants, which traditionally have limited size due to synthesis costs, and random or biased composition. Valuable insights have been gained, but precise control of expression in redesigned synthetic genes remains elusive. The proposed algorithmic research involves combinatorial design of synthetic gene variants to aid the construction of large scale, purposed libraries. The aim is to assay the most important sequence features which determine gene expression, while minimizing experimental cost and maximizing the exploration of the coding landscape. Proposed design, synthesis and wet-lab evaluation of reporter gene variants with modified characteristics will help determine their quantitative effect on expression in a model organism and validate our algorithmic designs.
Intellectual merit: Upon successful completion, this project will make major advances in the computational and life sciences, through new algorithmic results in combinatorial design of diverse gene libraries with minimized cost, and fundamental discoveries regarding gene expression. PIs expect their design methodologies to fuel an array of new discoveries by enabling high throughput cost effective experiments to study the effects of sequence features of genes and pathways, and help gain important insights by comparing experimental observations with long standing computational and theoretical models.
Broader Impact: The algorithms and software developed with this award will be used to design the next generation of large-scale synthetic construct experiments, which will enable optimized redesign of genetic elements to be transferred from one organism to another, adapting to an altogether different environment. The primary impact will ultimately rest with the science done using these techniques, such as drug and chemical synthesizing microorganisms with improved yields, rapidly produced vaccines, and CO2 transforming micro-algae. The educational impact includes active promotion of computational and synthetic biology in lectures towards graduate and undergraduate students, and dissemination of research findings and data through web accessible repositories.
