[GUT-NAT] Gut Commensals as Next-Generation Chassis for Natural Product Therapeutics
Ente: EC
Scadenza: 2029-03-31
Importo max: 200.400 EUR
Paese: EU
Descrizione
Recent advances in synthetic biology and microbiome research have highlighted the pivotal role of the human gut microbiome not only in maintaining gastrointestinal health but also in regulating systemic processes such as metabolism, immunity, and neurobiology. In this context, engineering commensal bacteria for precise, localized therapeutic delivery with minimal side effects is an emerging frontier. To date, most engineered microbial therapeutics have focused on probiotic species such as Escherichia coli or Lactobacillus spp.—due to their genetic tractability. However, these species often struggle to engraft durably in the complex gut environment. Moreover, commensal strains developed so far have been limited to heterologous production of protein-based therapeutics. To broaden the therapeutic arsenal, GUT-NAT aims to develop Clostridium leptum, a prevalent human gut commensal, into a next-generation, genetically programmable chassis for the biosynthesis of clinically relevant and functionally diverse therapeutic natural products. My preliminary results demonstrated successful genetic manipulation of C. leptum. GUT-NAT’s goals will be achieved through three integrated objectives, leveraging my expertise in microbial genetic engineering, natural product biosynthesis, and analytical chemistry: (1) characterization of genetic regulatory elements in C. leptum. (2) metabolic engineering, and (3) biosynthesis of anticancer natural products in C. leptum using state-of-the-art tools such as PacBio long-read genome sequencing, high-efficiency inducible CRISPR-based genome editing, and advanced mass spectrometry. Together, these efforts will (i) unlock the synthetic potential of an underexplored gut commensal, (ii) establish a robust and persistently engrafted chassis for the production of natural product therapeutics, and (iii) accelerate the discovery of novel bioactive metabolites from anaerobic microbiota, thus addressing a critical gap in microbiome synthetic biology.
Settori: Horizon Europe Topics
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