Objective
Our intestinal tract offers an attractive environment for bacteria. The beneficial bacteria of our microbiota feast on undigested foods and provide numerous health benefits. Enteric pathogens see this environment as an entry point for infection. Both groups influence each other, creating a tripartite interaction with us, the host. Understanding this interaction represents an emerging research area to combat infections poised to improve human health.
Bacteroides are key commensals in these triangular interactions, as they produce diffusible intermediates as part of their metabolism that are utilized by pathogens and the host. These metabolites arise from the action of ~100 polysaccharide utilization loci (PUL) that have been a major focus, from biochemistry to gene regulation. While the field has focused mostly on transcriptional PUL control, recent work from my group and others demonstrated that Bacteroides employ noncoding RNAs to regulate metabolic genes. These insights raise the questions: what is the mechanism by which noncoding RNAs regulate PUL, and how do these mechanisms fit within the tripartite interaction between Bacteroides, the host, and pathogens?
In GUT-CHECK, I hypothesize that PUL regulation integrates transcriptional and RNA-mediated post-transcriptional control, which in turn shape the outcome of host-pathogen interactions. To test this hypothesis, I will answer three specific questions:
1) How is PUL expression regulated?
2) How does PUL regulation impact interactions with pathogens and the host?
3) To what extent can PUL regulation be manipulated to thwart pathogen invasion?
The proposed work will incorporate a three-way model for Bacteroides, host tissue, and a pathogen along with modern techniques such as CRISPR-based screens and Triple RNA-seq. The functional insights gained will establish fundamental understanding of host-microbiota-pathogen interaction and may lead to novel RNA-based treatments for intestinal infections.
Fields of science (EuroSciVoc)
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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.
This project's classification has been validated by the project's team.
Keywords
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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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)
MAIN PROGRAMME
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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-2021-STG
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97070 Wuerzburg
Germany
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