Project description
Glial cells at the heart of MS progression
Multiple sclerosis (MS) is usually studied through immune cells that attack the brain. Researchers are now focussing on glial cells. The ERC-funded MiST-MS project aims to explore how the ageing and stress responses of glial cells could cause long-term inflammation and disability. Specifically, microglia derived from human stem cells and CRISPR screening are being used to find the molecular pathways that influence the resilience or vulnerability of these cells. On the patient side, the goal of the project is to develop treatments by comparing glial and neuronal responses in people who have chronic active lesions to those who do not. It aims to establish new targets for therapies that can slow or stop MS progression.
Objective
Shifting from the traditional focus on central nervous system-targeting lymphocytes, MiST-MS posits that glial responses, particularly cellular senescence, are required to compartmentalized self-sustaining chronic inflammation in multiple sclerosis (MS) and related long-term clinical outcomes, including disability. MiST-MS is specifically designed to address the urgent need to identify new therapeutic targets to halt MS clinical progression through two interconnected research lines.
The project will first identify cell-specific perturbations and molecular pathways associated with inflammation-driven early brain aging using MS human iPSC-derived microglia and genome-wide CRISPR-Cas9 screenings. By employing cutting-edge computational methodologies (single-cell CRISPR-seq, multi-omics integration, composite assessment, and cellular networking/signaling), MiST-MS offers a unique opportunity to identify and dissect mechanisms underlying microglia resilience versus vulnerability and their impact on stress responses, both independently and within the context of hiPSC-derived inflamed glia-enriched brain organoids. MiST-MS represents a ground-breaking modeling pipeline to study inflammation-driven early brain aging in MS.
At the patient-level, since MS patients with evidence of smoldering inflammation (marked by the presence of chronic active lesions by in vivo MRI) exhibit poor tissue repair capacity and worse clinical outcomes, the project will also aim to identify common and divergent glial and neuronal responses between MS patients with and without chronic active lesions generating human iPSC lines for personalized medicine applications.
In summary, MiST-MS is a highly innovative interdisciplinary project that provides an unprecedented understanding of microglia states in response to injury and streamlines the rational design of future therapies to mitigate chronic inflammation-driven premature brain aging and halt MS clinical progression.
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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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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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-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.
20072 PIEVE EMANUELE
Italy
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.