Project description
How bacteria manipulate the cell’s skeleton
Actin filaments are the skeleton and muscles of our cells. They help cells move, grow, and repair themselves. But some bacteria, such as Shigella and Listeria, have learned to exploit this system, using special proteins to navigate through cells and spread infection. In this context, the ERC-funded Actin in Action project is uncovering exactly how this happens at the atomic level. Using advanced cryo-electron microscopy and tomography, researchers are mapping how bacterial proteins manipulate actin and how cells respond. By combining structural biology, proteomics, and transcriptomics, they aim to create the first detailed model of this ‘actin takeover’. These insights could help develop smarter ways to stop dangerous bacterial infections.
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.
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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.
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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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HORIZON.1.1 - European Research Council (ERC)
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(opens in new window) ERC-2025-STG
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9712CP Groningen
Netherlands
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