Project description
Uncovering bacteria’s secret weapons
For years, scientists thought specialised secretion systems were exclusive to Gram-negative bacteria. But Gram-positive bacteria, including harmful pathogens like Mycobacterium tuberculosis, have a powerful exception: the type VII secretion system (T7SS). This complex machinery does not just export proteins involved in infection; it also plays a surprising role in microbial warfare between bacteria. The ERC-funded CombaT7 project brings together top researchers tto decode the mysteries of T7SS in important mycobacterial pathogens like M. tuberculosis and M. abscessus. Using cutting-edge tools like cryo-EM and lung-on-a-chip models, the team will map the system’s structure, identify new protein targets, and uncover how it influences both disease and bacterial competition, laying the groundwork for new ways to fight infection.
Objective
Bacteria interact with their environment via specialised secretion systems that deliver proteins outside of the cell. Due to a bias in research efforts, for many years such systems were assumed to be unique to Gram-negative bacteria. A major exception is the type VII secretion system (T7SS), which is widespread in Gram-positive bacteria and actinobacteria, including the important human pathogen Mycobacterium tuberculosis. The T7SS is a complex secretion apparatus that exports folded proteins and even protein complexes. While secreted substrates are well-known for being crucial players in host-pathogen interactions, our recent data indicate that specific substrates of the relevant opportunistic pathogen Mycobacterium abscessus and the fish pathogen Mycobacterium marinum are also involved in interbacterial antagonism. This makes T7SSs important factors to understand microbial interactions, also for the understudied part of the microbial world.
While the mechanism of secretion via T7SSs remains little understood, our preliminary data show that not only their roles but also their substrates are more diverse than thus far thought. Here, we unite leading experts in microbiology, structural biology, cell biology, and biophysics to spearhead research on mycobacterial T7SSs and their roles in both interbacterial and host-pathogen interactions. In this unique consortium, we will (i) define the full trans-envelope T7SS by atomic force microscopy and cryo-electron microscopy, (ii) study the mechanism of transport by creating translocation intermediates, (iii) expand the set of T7SS substrates by extensive proteomics and bioinformatics analysis, and (iv) visualise the role of T7SS in bacterial warfare and host-pathogen interactions using microfluidics, innovative lung-on-a-chip infection models and time-lapse microscopy. This will deliver a deep mechanistic understanding of the diverse roles of mycobacterial T7SSs and provide clues to exploit these systems to combat infections.
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.
- agricultural sciences agriculture, forestry, and fisheries fisheries
- natural sciences biological sciences microbiology bacteriology
- natural sciences physical sciences optics microscopy
- medical and health sciences clinical medicine pneumology tuberculosis
- natural sciences biological sciences molecular biology structural biology
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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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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-SYG - HORIZON ERC Synergy 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-2024-SyG
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1081 HV Amsterdam
Netherlands
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