Project description
Targeting pro-oncogenic biofilms in the colon
Colorectal cancer (CRC) development is linked to specific pathogenic bacteria known to disrupt gut epithelial integration and to cause inflammation. These bacteria employ a communication process known as quorum sensing to coordinate their behaviour and form invasive biofilms. With the support of the Marie Skłodowska-Curie Actions programme, the BIFCOLC-QS project aims to harness the concept of quorum sensing to design an innovative approach for early CRC detection. Researchers propose to engineer a probiotic strain that can sense specific molecules secreted by CRC-causing pathogenic bacteria. The strain will express an enzyme that can disrupt these biofilms and kill the pathogenic bacteria, offering a novel strategy for early CRC treatment.
Objective
Colorectal cancer (CRC) development and progression have been linked to the presence of pro-oncogenic bacterial strains in the intestine, such as Fusobacterium nucleatum, pks+ Escherichia coli and enterotoxigenic Bacteroides fragilis. These pathogenic bacteria produce toxins that can disrupt gut epithelial integrity resulting in heightened pro-inflammatory response, enhanced DNA mutations, and increased cell proliferation, which can eventually lead to adenoma formation. In addition, these bacterial pathogens show increased genotoxicity by forming invasive polymicrobial biofilms, thereby resulting in CRC development. Recently it has been reported that anatomical location plays a crucial role in CRC development, progression, microbial colonization, response to therapies and disease outcome. Indeed, right-sided CRC is generally associated with pro-oncogenic bacterial biofilms and is known to have an overall worse prognosis compared to left-sided CRC. Pathogenic bacteria use quorum sensing (QS) machinery in the gut for their communication, which is essential for biofilm formation. We aim to develop an intervention strategy employing QS machinery to engineer a probiotic bacterial strain with sensing and killing properties to detect and target these pro-oncogenic polymicrobial biofilms. The sensor device will detect autoinducers produced by pathogenic bacteria on encountering their biofilms, activating the killing device. The killing device expresses a biofilm degrading enzyme, Dispersin B, which will disrupt these biofilms and eventually kill the pathogenic bacteria residing in these biofilms by the type VI secretion system. These polymicrobial biofilms can act as a marker of CRC and help to understand the role of CRC-associated pathogenic bacteria in CRC development, which can eventually serve as a basis for developing future strategies for the diagnosis and treatment of CRC and other intestinal disorders associated with biofilms formed by pathogenic bacteria.
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
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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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
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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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) HORIZON-MSCA-2022-PF-01
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69117 Heidelberg
Germany
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