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Reducing “noise” in gene expression

New system for producing proteins in bacteria

Oeiras, 10.11.2017

Synthetic biologists want to engineer microorganisms that produce proteins and other molecules and interact with the environment and other organisms in predictable ways. To do this, they must develop tools to observe cell behavior with as much precision as possible — sometimes down to the single-molecule level. However, it is difficult to engineer bacteria so that all cells produce a low number of molecules with little cell-to-cell variation, called gene expression “noise”.

Zach Hensel, principal investigator at ITQB NOVA, has just developed a protein expression system that combines two strategies that reduce cell-to-cell variation and also make it easier to tune average expression levels. He is using this system to watch the dynamics of individual molecules in living bacteria cells.

The results were published in open access magazine PLoS ONE, after being shared at bioRxiv, a website used by biologists to share research results quickly between peers and receive feedback on manuscripts before they are published by journals. As one of Zach Hensel’s peers pointed out about this work “Interesting idea and rare single author synthetic biology paper.” All scientists interested in adopting this system in their own labs can get the plasmids developed by Zach Hensel from the non-profit DNA repository Addgene, now available.

“In our lab we are using this system in almost all of our experiments. It’s not a new idea to use negative feedback or bicistronic expression to reduce noise, but we hope what we have made will make it easier for other labs to apply these principles in their experiments." says Zach Hensel. "Preprint and open access resources such as bioRxiv and Addgene are invaluable for a new lab looking to get feedback on our work.”

 

Original article

PLOS ONE 12(10): e0187259 doi.org/10.1371/journal.pone.0187259

A plasmid-based Escherichia coli gene expression system with cell-to-cell variation below the extrinsic noise limit

Zach Hensel

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