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Integrating a novel layer of synthetic biology tools in Pseudomonas, inspired by bacterial viruses

Project description

Learning from the best: viral predators teach us about genetic control

News that a virus is on the loose that could infect our cells, hijack their cellular machinery forcing them to produce viral products rather than their own, and eventually burst out of our cells killing them and going on their merry way would be terrifying. This is exactly what bacteriophages do, fortunately to bacterial cells and not to ours. Their ability to command and control their hosts' gene expression has evolved over billions of years, and the EU-funded BIONICbacteria project is planning to harness this accumulated phage expertise for a synthetic biology toolbox. The team will target designer bacteria for biotech fermentation and vaccine design.

Objective

As nature’s first bioengineers, bacteriophages have evolved to modify, adapt and control their bacterial hosts through billions of years of interactions. Indeed, like modern synthetic biologists aspire to do, bacteriophages already evade bacterial silencing of their xenogeneic DNA, subvert host gene expression, and co-opt both the central and peripheral metabolisms of their hosts. Studying these key insights from a molecular systems biology perspective, inspired us to develop these evolutionary fully-adapted phage mechanisms as a next-level layer of synthetic biology tools. Thus, BIONICbacteria will provide conceptual novel synthetic biology tools that allow direct manipulation of specific protein activity, post-translational modifications, RNA stability, and metabolite concentrations.

The goal of BIONICbacteria is to pioneer an unconventional way to perform synthetic biology, tapping an unlimited source of novel phage tools genetic circuits and phage modulators. To achieve these goals, we will apply and develop state-of-the-art technologies in molecular microbiology and focus on three principal aims:

(1) To exploit new phage-encoded genetic circuits as synthetic biology parts and as intricate biotechnological chassis.

(2) To build synthetic phage modulators (SPMs) as novel payloads to directly impact the bacterial metabolism in a targeted manner.

(3) To create designer bacteria by integrating SPMs-containing circuits into bacterial strains as proof-of-concepts for applications in industrial fermentations and vaccine design.

This proposed “plug-in” approach of evolutionary-adapted synthetic modules, will allow us to domesticate Pseudomonas strains in radically new ways. By building proofs-of-concept for applications in industrial fermentations and vaccine development, we address key problem in these areas with potentially high-gain solutions for society and industry.

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Coordinator

KATHOLIEKE UNIVERSITEIT LEUVEN
Net EU contribution
€ 1 998 750,00
Address
Oude markt 13
3000 Leuven
Belgium

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Region
Vlaams Gewest Prov. Vlaams-Brabant Arr. Leuven
Activity type
Higher or Secondary Education Establishments
Links
Other funding
€ 0,00

Beneficiaries (1)