Project description
How bacterial fortresses crumble: a potential alternative to antibiotics
Many pathogens shield themselves from immune system detection by hiding in membrane-bound compartments they create by hijacking the cell’s organelles. Destabilising these pathogen-containing vacuoles (PCV) could be therapeutic. The ERC-funded INCLUSION-INTEGRITY project aims to investigate the molecular mechanisms of PCV stability and how destabilisation might be used as an alternative to antibiotics. Researchers will use proteomic, lipidomic and microscopic approaches to investigate differences between stable and unstable PCV. Microscopic and genetic approaches will help elucidate the molecular basis of instability and how to guide its outcome to cell death or survival. Finally, a study of whether infection causes long-term damage will point to whether therapeutics should target cell death or cell survival.
Objective
Many clinically important pathogens invade human cells and evade their intrinsic defenses by hiding within pathogen-containing vacuoles (PCVs). Hence, it may be feasible to combat such microbes by deliberately destabilizing their PCVs. To promote progress towards such an innovative therapeutic concept, I propose a 5-year research program in which my team will generate a molecular mechanistic understanding of how the PCV is maintained, how it can be destabilized, and how the consequences of PCV destabilization can be steered towards a beneficial outcome. We will focus on the inclusion, i.e. the PCV of Chlamydia trachomatis, as the strong host cell dependence of this leading bacterial cause of ocular and urogenital infections makes it an exquisite target for pioneering PCV-destabilizing strategies. In AIM 1, we will leverage inclusion-destabilizing conditions we identified previously and state-of-the-art proteomic, lipidomic, and microscopic approaches to address the fundamental question of what distinguishes unstable from stable inclusions. In AIM 2, we will build on these findings and apply our unique microscopic reporters for inclusion damage and a robust genetic approach to identify the molecular basis of inclusion stability, determine how distinct forms of inclusion destabilization interact with each other and with host cellular defense programs, and find ways to steer the outcome towards either host cell death or survival. Finally, in AIM 3, we will clarify which of those two outcomes therapeutic targeting should aim for by isolating cells cured from infection via inclusion destabilization, followed by systematic cell biological and omics investigations to determine if infection causes long-lasting damage to host cells. By filling critical knowledge gaps in the field of host-pathogen interactions, I expect this project to pave the way for the future design of innovative precision antibiotics for our battle against intracellular 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.
This project's classification has been human-validated.
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 human-validated.
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)
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-2025-COG
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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.
901 87 UMEA
Sweden
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