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

Description du projet

Apprendre des meilleurs: les prédateurs viraux nous enseignent le contrôle génétique

Il serait terrifiant d’apprendre qu’un virus en liberté pourrait infecter nos cellules, détourner leur machinerie cellulaire pour les forcer à synthétiser des produits viraux plutôt que les leurs et, à terme, faire éclater nos cellules et les tuer pour poursuivre leur chemin. C’est exactement ce que font les bactériophages, heureusement aux cellules bactériennes et non aux nôtres. Leur capacité à commander et à contrôler l’expression génétique de leurs hôtes a évolué au cours de milliards d’années, et le projet BIONICbacteria, financé par l’UE, prévoit d’exploiter ce savoir-faire bactériophage accumulé pour créer une boîte à outils de biologie synthétique. L’équipe ciblera les bactéries de conception pour la fermentation biotechnologique et la conception de vaccins.

Objectif

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.

Régime de financement

ERC-COG - Consolidator Grant

Institution d’accueil

KATHOLIEKE UNIVERSITEIT LEUVEN
Contribution nette de l'UE
€ 1 998 750,00
Adresse
OUDE MARKT 13
3000 Leuven
Belgique

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Région
Vlaams Gewest Prov. Vlaams-Brabant Arr. Leuven
Type d’activité
Higher or Secondary Education Establishments
Liens
Coût total
€ 1 998 750,00

Bénéficiaires (1)