Project description
Decoding gene regulation in gut microbiota
The human gastrointestinal gut harbours a large number of commensal bacteria which play a key role in homeostasis and host metabolism. The so-called gut microbiota responds to cues by modulating their gene expression. The ERC-funded REGUBIOME project will investigate transcriptional responses to biotic and abiotic stimuli in two key gut bacteria: the probiotic Lacticaseibacillus rhamnosus and the pathobiont Fusobacterium nucleatum. Researchers will use CRISPR interference, microfluidics and transcriptomics to map gene regulatory networks and interactions with other microbes. Findings will provide important insight into gut microbial regulation and identify potential new targets for modulating bacterial activity to improve health.
Objective
Bacteria from the gut microbiota constantly interact with a range of abiotic and biotic factors. Perturbations in these factors, such as nutrient depletion or exposure to exogenous microbes, require specific bacterial responses that involve tightly controlled gene expression changes. However, the transcriptional regulation mechanisms promoting such gene expression changes remain poorly understood despite their importance.
REGUBIOME will characterize how responses to specific biotic and abiotic stimuli are regulated at the transcriptional level in two health-associated gut bacteria: one probiotic (Lacticaseibacillus rhamnosus) and one pathobiont (Fusobacterium nucleatum, previously linked to colorectal cancer). This project relies on combining experimental platforms of increasing complexity to systematically characterize the responses of these two bacteria to defined biotic and abiotic factors, and to evaluate how these responses impact host health. First, I will develop a novel high-throughput functional screening tool, coupling CRISPR interference, microfluidic platforms for single-cell isolation, and transcriptomic profiling of isolates. By applying this tool to in vitro monocultures, I will reconstruct the first-ever gene regulatory networks in these bacteria and identify mechanisms of response to different abiotic factors. Second, microfluidic co-culturing of these two strains with multiple other bacteria, coupled with metatranscriptomic profiling, will reveal the regulatory mechanisms mediating the interactions with other microbiome members. Lastly, in vivo work in mouse models will shed light on how the host colonic environment impacts gene expression in these health-associated bacteria.
Altogether, REGUBIOME will provide proof of the importance of gut bacterial gene regulation networks to host health. Besides, by uncovering gene regulatory mechanisms in microbiome bacteria, REGUBIOME will provide novel actionable targets for microbiota modulation strategies.
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 microbiology bacteriology
- medical and health sciences clinical medicine oncology
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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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HORIZON.1.1 - European Research Council (ERC)
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Topic(s)
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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
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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.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2023-STG
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46012 Valencia
Spain
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