Project description
The genetic basis of viral immune response variability
Plasmacytoid dendritic cells (pDCs) are specialised immune cells that play a crucial role in the body's defense against viral infections and in modulating immune responses. Accumulating evidence indicates the presence of functionally distinct pDC subsets which may explain the interindividual variations in antiviral responses and autoimmune diseases. The ERC-funded ImmGenDC project will sequence the genome of single pDCs from healthy individuals across three ancestry populations. The research team aims to identify novel pDC subtypes and their regulatory circuits to enhance our understanding of immune response variability and aid the development of precision medicine interventions for autoimmune diseases.
Objective
Antiviral immunity and autoimmune diseases exhibit high interindividual variability. Despite intensive research, the genetic and molecular basis of this variability is incompletely understood. A key player of the immune system is the plasmacytoid dendritic cell(pDC). Recent single-cell work revealed functionally distinct pDC subsets. Considering that pDCs respond to many pathogens, this highlights a previously underappreciated functional diversity of pDCs.
I hypothesize that the genetic regulation of pDCs plays a fundamental role in explaining antiviral response and autoimmune variability. Based on my previous work on immune cells, this genetic regulation is expected to be highly context-specific depending on cell type, cell response, ancestry populations and sex among other factors.
The overarching goal of this proposal is to elucidate the context-specificity of immune response and its genetic regulation in pDCs to improve our understanding of human antiviral response variation and pinpoint undiscovered disease pathways of autoimmune diseases.
To this end, I will generate population-scale, linked scATAC-, sc3’RNA- and scLong-read cDNA-seq data of baseline and TLR7-stimulated pDCs from healthy individuals across three ancestry populations. I will identify novel pDC subtypes and their immune-regulatory circuits by integrated multiome analyses. Molecular quantitative trait loci(QTLs) and their degree of context-specificity will be used to build prediction models of genetically determined immune responsiveness and decode autoimmune disease loci to develop mechanistically anchored interventions for precision medicine.
ImmGenDC will gain fundamental insights into the variability of antiviral immune response that will enable the development of new treatments as exemplified by the current pandemic. Importantly, ImmGenDC will also identify genetic determinants of immune variability across diverse ancestry populations thus paving the way for equitable access to medicine.
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)
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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.
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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
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2022-STG
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80539 MUNCHEN
Germany
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