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Gut Commensals as Next-Generation Chassis for Natural Product Therapeutics

Project description

Programming gut bacteria for medicine delivery

The human gut microbiome plays a major role in digestion, immunity, metabolism and overall health. Scientists are increasingly exploring ways to engineer beneficial gut bacteria so they can produce medicines directly inside the body with fewer side effects. However, current microbial therapies often use bacteria that do not engraft well in the gut and display limited potential in the production of therapeutics. With the support of the Marie Skłodowska-Curie Actions programme, the GUT-NAT project aims to develop a new therapeutic platform based on Clostridium leptum, a common and stable gut bacterium. Researchers will programme this strain to manufacture natural compounds, including potential anticancer agents, opening new possibilities for microbiome-based treatments.

Objective

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.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2025-PF

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Coordinator

VIB VZW
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 200 400,00
Address
SUZANNE TASSIERSTRAAT 1
9052 ZWIJNAARDE - GENT
Belgium

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Region
Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent
Activity type
Research Organisations
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Total cost

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