Project description
Putting gut bacteria metabolites to the test
The human gut microbiome plays a fundamental role in health, and alterations in its composition lead to various diseases. Biosynthetic gene clusters (BGCs) are potentially implicated in microbiome structure, but very few have been experimentally validated for their deleterious metabolic impact on the human host. The scope of the EU-funded SMs-Gut project is to extend these findings and identify specialised metabolites in the gut with a fundamental role in the development of inflammatory bowel disease and colorectal cancer. Scientists will employ a combination of bioinformatics, synthetic biology and analytical technologies to decipher the biological functions of the discovered compounds.
Objective
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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences synthetic biology
- natural sciences biological sciences genetics DNA
- medical and health sciences clinical medicine gastroenterology inflammatory bowel disease
- medical and health sciences clinical medicine oncology colorectal cancer
- natural sciences biological sciences microbiology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2019
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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.
01069 DRESDEN
Germany
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.