Objective
Formation of Tertiary Lymphoid Structures (TLS) is a recurring consequence of chronic tissue inflammation and autoimmunity, as well as several solid tumours. TLS originate in various tissues from infiltrating cells attracted by local signalling cascades. These structures can enhance local immune response by, similarly to Secondary Lymphoid Organs (SLO), functioning as spots for lymphocyte activation upon antigen recognition. However, the cellular interactions driving TLS emergence and function across tissues are not fully known. This proposal aims to unravel and characterise the cell-cell interactions involved in the formation and maintenance of TLS, in particular their tissue specificity and relationship to autoimmune diseases. A comprehensive understanding of intercellular interactions will be obtained from publicly available and newly generated single-cell RNA-sequencing (scRNA-seq) datasets from TLS-containing tissues of autoimmunity patients. Molecules involved in key signalling interactions will be spatially resolved by assessing their tissue expression using spatial transcriptomics. Then, using mouse models where TLS triggering can be controlled, scRNA-seq data will be obtained to outline a time course of TLS formation in different tissues, revealing the temporal role of the discovered interactions and their specific function in each tissue and when compared with SLOs. Finally, regulation and downstream effects of ligands and receptors will be unraveled with multiome (RNA+open chromatin) sequencing using human tonsil organoids. The observed effects will be generalised to other tissues using machine learning and deep learning models, resulting in a tissue-specific reference of signalling and regulatory genes controlling TLS biogenesis. Overall, this project aspires to provide a detailed look into TLS biology, while defining the bases for their therapy-oriented manipulation.
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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.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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
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
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) HORIZON-MSCA-2023-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.
1649-035 LISBOA
Portugal
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.