Project description
Chromatin dynamics and immunological memory
Our immune system has a unique ability to remember foreign pathogens and to mount a strengthened and rapid response upon a second encounter. Memory T cells play an instrumental role in generating immunity and their dysfunction has been linked to disease including autoimmunity. However, it is currently unknown how these cells reorganise their chromatin to rapidly alter the expression of inflammatory genes. Funded by the Marie Skłodowska-Curie Actions programme, the Remin-T project aims to shed light into the epigenetic mechanisms of immunological memory. Researchers will employ a cutting-edge methodology to investigate how the genome folds to accommodate a rapid transcriptional response in memory T cells.
Objective
T lymphocytes are essential for immunity to pathogens and malignancies. Activated T cells can retain a memory imprint of their adversary (e.g. a virus), enabling them to respond more rapidly and vigorously to any subsequent encounters. While memory T cell formation is critical for successful vaccination and anti-tumor immunity, dysfunctional memory T cells are a common feature of human disease, including allergy, autoimmunity and cancer. T cell activation emerges from changes in gene expression dictated by intricate chromatin dynamics. Recently, 3D chromatin folding emerged as a key regulator of transcriptional control by ensuring correct communication between regulatory elements and their target genes. How memory T cells leverage three-dimensionally organized chromatin configurations to achieve rapid re-activation of specific inflammatory genes is unclear. Hence, the molecular mechanisms that control and maintain immunological memory remain poorly understood. To address this issue, I propose an innovative molecular strategy to dissect immunological memory in primary human CD4+ T cells that combines cutting-edge genome-wide analyses of gene expression, chromatin state and three-dimensional (3D) genome folding with CRISPR/Cas9-based functional assays. This approach will generate the first integrated multidimensional epigenome atlas of a human T cell memory recall response, yielding molecular circuits of genes, regulatory elements and biological pathways underlying human immunological memory. Multimodal single cell genomics assays will reveal the nature of transcriptome-epigenome crosstalk in individual T cells and the heterogeneity of memory recall. These insights will force a breakthrough in our understanding of how human immune cells maintain specific transcriptional programs for launching rapid and tailored responses upon re-activation, and how this feeds into susceptibility to develop disease.
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.
- natural sciences biological sciences microbiology virology
- medical and health sciences clinical medicine oncology
- medical and health sciences clinical medicine allergology
- natural sciences biological sciences genetics genomes
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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.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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) HORIZON-MSCA-2021-PF-01
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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.
3015 GD Rotterdam
Netherlands
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