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

Descrizione del progetto

Imparare dai migliori: i predatori virali ci insegnano il controllo genetico

La notizia di un virus in circolazione in grado di infettare le nostre cellule, dirottare il loro meccanismo cellulare costringendole a produrre prodotti virali piuttosto che i propri, e alla fine di erompere dalle nostre cellule uccidendole, proseguendo poi allegramente per la loro strada sarebbe terrificante. Questo è esattamente quello che fanno i batteriofagi, fortunatamente alle cellule batteriche e non alle nostre. La loro capacità di comandare e controllare l’espressione genica dei loro ospiti si è evoluta nel corso di miliardi di anni e il progetto BIONICbacteria, finanziato dall’UE, sta pianificando di sfruttare questa esperienza accumulata sui fagi per un set di strumenti di biologia sintetica. Il team si focalizzerà sui batteri per la fermentazione biotecnologica e la progettazione di vaccini.

Obiettivo

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.

Meccanismo di finanziamento

ERC-COG - Consolidator Grant

Istituzione ospitante

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

Mostra sulla mappa

Regione
Vlaams Gewest Prov. Vlaams-Brabant Arr. Leuven
Tipo di attività
Higher or Secondary Education Establishments
Collegamenti
Costo totale
€ 1 998 750,00

Beneficiari (1)