ISMBE 2020

IGEM TAU 2020 - Constructing an Evolutionary Stable Genetic Circuit

Matan Arbel 1 Karin Sionov 2 Itai Katir 3 Doron Naky 3 Omer Edgarm 4 Bar Glickstein 2 Noa Kraicer 2 Elinor Nadir 3 David Kenigsberger 3 Hadar Ben Shoshan 2 Einav Saadia 3 Sophie Vinokour 2 Larissa Fine 2 Tamir Tuller 2
1Tel Aviv University, Israel
2Tel Aviv University, Israel
3Tel Aviv University, Israel
4Tel Aviv University, Israel

Advances in synthetic biology have led to an arsenal of proof-of-principle bacterial circuits that can be leveraged for applications ranging from therapeutics to bioproduction. A unifying challenge for most application is the presence of strong selective pressure that will led to an unstable evolutionary genetic construct that will undeniably cease to work in a short period of time. This predicament is hindering any major advances in biosynthetic engineering, or more importantly, its implementation. Our group is hellbent on creating a system that will significantly prolong the half-life of such genetic circuits.

Using bioinformatics tools and basic genetic engineering, our group suggests a way to transcriptionally interlock a desired genetic circuit and an essential protein of the organism. This way, a big proportion of the mutation that can occur to the genetic circuit will lead to a defect in the transcription of the essential protein, leading to the lethality of the mutated induvial. Thus, preventing the lose of the genetic circuit with its metabolic burden, a lose that if not hampered, eventually will lead to the genetic construct erosion under the selection pressure.

While there is still a lot of work to be done, our system can be the first step toward a genetically engineered evolutionary stable organism. Those organisms, whatever bacteria, fungus or Archaea could be the building blocks for the new future biosynthetic engineers are envisaging.