Descrizione del progetto
Mettere alla prova i metaboliti dei batteri intestinali
Il microbioma intestinale umano svolge un ruolo fondamentale nella salute e le alterazioni nella sua composizione causano varie malattie. I cluster di geni biosintetici sono potenzialmente implicati nella struttura del microbioma, ma sono molto pochi quelli convalidati a livello sperimentale per il loro impatto metabolico deleterio sull’ospite umano. Il campo di applicazione del progetto SMs-Gut, finanziato dall’UE, prevede l’ampliamento di questi risultati e l’identificazione dei metaboliti specializzati nell’intestino con un ruolo fondamentale nello sviluppo della malattia infiammatoria intestinale e del cancro del colon-retto. Gli scienziati impiegheranno una combinazione di bioinformatica, biologia sintetica e tecnologie analitiche per decifrare le funzioni biologiche dei composti scoperti.
Obiettivo
Composition changes of the human gut microbiome has been associated with a series of diseases. However, little is known about the mechanism of this microbiome alteration. Recent in silico studies revealed thousands of biosynthetic gene clusters (BGCs) that encode diverse types of specialized metabolites from human microbiomes. Many of these molecules are potentially involved in shaping microbiome structure or directly affect host cell and contribute to disease development. To date, only colibactin, a hybrid polyketide/non-ribosomal peptide produced by Escherichia coli in human gut, has been experimentally validated for its deleterious metabolic impact on human host and linked to the development of colorectal cancer (CRC). Thus, this project aims to expand the knowledge of specialized metabolites produced by gut microbiome and unravel their role in development of inflammatory bowel disease (IBD) and CRC. State-of-the-art bioinformatic, synthetic biology and chemical-analytic technologies will be used to tackle this challenge. In silico identification of BGCs will be facilitated by sequence homology search and the occurrence of function-related resistant makers. The cloning process will be realized by either capturing native BGCs, adopting polymerase amplification or using synthetic DNA, followed by HiFi DNA assembly, Red/ET recombineering based DNA integration method or combining of both strategies. The chemical diversity of these specialized metabolites will be unlocked by heterologous expression of the cloned BGCs and structure elucidation of the produced molecules. The biological functions of the discovered compounds will be established by probing their genotoxicity and cytotoxicity in vitro with human intestinal cell lines.
Campo scientifico
CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP.
CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP.
- natural sciencesbiological sciencessynthetic biology
- natural sciencesbiological sciencesgeneticsDNA
- medical and health sciencesclinical medicinegastroenterologyinflammatory bowel disease
- medical and health sciencesclinical medicineoncologycolorectal cancer
- natural sciencesbiological sciencesmicrobiology
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
01069 Dresden
Germania