Primary Investigator

Email

Institution

Dickerman, Allan W.

dickerman@vt.edu

Virginia Tech

Abstract
Cells routinely perform complex computational tasks that enable them to control the orchestration of thousands of genes and communicate with other cells to manifest emergent properties such as growth and differentiation.Understanding and engineering the algorithms underlying the complex computational machinery of cells should have significant impact in science and technology,particularly biotechnology, biocomputation and medicine. Several notable recent reports demonstrate that it is possible to design and construct simple de novo genetic circuits such as a switch and an oscillator in Escherichia coli .This work also revealed that implementation of even the most simple circuits in vivo requires tedious optimization of often poorly- understood protein-DNA interactions and mRNA and protein stabilities,among other parameters.We propose to develop efficient,evolutionary design strategies for constructing functional de novo genetic circuits.We will apply methods of molecular evolution,which have proven highly successful for engineering proteins with improved or altered properties,to complex genetic systems involving multiple repressors,operators,and promoters.We believe that evolution will prove to be generally applicable for optimizing individual devices as well as complex genetic circuits,and our goal will be to demonstrate how evolutionary searches are best performed in order to build libraries of devices and assemble them into functional circuits.