Objective
Actin and its associated regulatory proteins are fundamental components of the cytoskeleton, playing a central role in nearly every process in eukaryotes. Remarkably, the intracellular pathogens Shigella and Listeria have evolved specialized proteins, known as effectors, to hijack this crucial system of the host. These effectors induce actin polymerization on the bacterial surface, allowing the pathogens to propel themselves within and between host cells through a process called actin-based motility (ABM). Despite the critical role of ABM in bacterial infections, the mechanism by which ABM effectors interact with and activate host cell proteins is not understood at the atomic level. In addition, the regulation mechanisms of ABM and the host cell response to the cytoskeletal manipulation remain unclear.
I therefore propose to elucidate the mechanisms of actin regulation during intoxication by ABM effectors. Using single-particle cryo-EM and cryo-electron tomography — techniques that have only become widely accessible in the past decade — I will determine the first high-resolution structures of ABM effectors and their complexes with actin-regulatory proteins. Building on my extensive expertise in studying actin and its associated proteins with these cutting-edge methods, I will develop a detailed mechanistic model of how ABM effectors orchestrate and regulate the host cytoskeleton, as well as how host cell proteins influence ABM within the cellular environment. Hypothesizing that cytoskeletal modulation by ABM effectors triggers cellular responses, I will employ a combination of proteomics and transcriptomics analyses to decipher how this manipulation of the actin cytoskeleton impacts host cell response pathways.
This study will provide atomic-level insights into actin cytoskeleton regulation during bacterial infection, laying the groundwork for developing targeted therapies against diseases like shigellosis and listeriosis, which pose major medical challenges.
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.
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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)
MAIN PROGRAMME
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Topic(s)
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.
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-ERC - HORIZON ERC Grants
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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) ERC-2025-STG
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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.
9712CP Groningen
Netherlands
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.