INTEGRATED CIRCUIT DESIGN

PROBING AND RESHAPING THE GENOME TO CONTROL CELL FATE

One challenge in synthetic biology is to integrate synthetic circuitry into larger transcriptional networks to mediate predictable cellular behaviors. While significant efforts have been devoted to the logical design of enhanced synthetic circuitry, less is understood regarding how cellular hardware and the three-dimensional structure of genetic elements affect circuits. The three-dimensional structure of DNA, influenced by local DNA topology (e.g. supercoiling) and the epigenome, modulates gene expression. Consequently, constructing robust transcriptional circuits requires understanding and accounting for the influence of DNA topology.

WHAT A TANGLED WEB WE WEAVE

Elucidating principles of three-dimensional circuit design

In a post-genomics era, the three-dimensional structure of the mammalian genome has emerged as a powerful mediator of cellular behavior. Our lab examines how local DNA topology and transcription interact to influence circuit performance.

TANGLES AS PROBES

Topologically-Affected Network of Genes Linking Expression to State

Insight into how DNA supercoiling directly impacts cellular events is limited. Methods for examining DNA topology require harvesting millions of cells for biochemical analysis. Assaying topological states in living cells via circuits constructed as probes represents an opportunity to examine how the structure of the genome influences cellular decision-making at the single-cell level. To address this issue, our lab will develops and characterizes circuits capable of translating changes in DNA supercoiling to changes in circuit output. Developing these tools enables us to utilize synthetic circuits as sensors to probe the transcriptional and topological dynamics of cell fate transitions