Project description
Determining the drivers of inflammatory skin disorders
Millions of people suffer from inflammatory skin disorders such as atopic dermatitis and psoriasis, which cause chronic discomfort and emotional distress. Current treatments often fail because they target late-stage inflammation rather than the underlying causes. A deeper understanding of the early mechanisms driving skin inflammation is crucial for developing more effective therapies. One key factor is inflammasome signalling in keratinocytes, which, if incorrectly regulated, can trigger excessive inflammation. In this context, the ERC-funded 4D-SkINFLAM project aims to map inflammasome activity with unprecedented precision. Using optogenetics, spatial transcriptomics, and AI-driven deep proteomics, researchers seek to uncover how specific inflammasomes contribute to skin disease. This could pave the way for targeted treatments, addressing a critical unmet medical need.
Objective
To ‘feel comfortable in one’s own skin’ is an idiom referring to one’s confidence in interacting with others. However, when the skin is inflamed, as in atopic dermatitis or psoriasis, patients carry a sub-stantial burden leading to opposite effects. Current therapies target redundant, late-stage inflammatory events but not the disease drivers, leading to heterogeneous and insufficient efficacy. Understanding the proximal mechanisms of inflammation will stimulate the development of better therapies.
Among the innate immune sensors for stress and microbes in keratinocytes, mutations in the NLRP1 and NLRP10 inflammasomes are linked to skin disorders. These molecules and the pro- and anti-inflammatory IL-1 family members they regulate are differentially expressed in the different layers of the epidermis. We hypothesize that inflammasome signaling in keratinocytes needs context-dependent and spatio-temporal control to avoid inflammation, which poses unique analytical and conceptual challenges.
Therefore, to understand how inflammasome signaling in specific keratinocytes drives skin inflammation, 4D-SkINFLAM will i. optogenetically activate specific inflammasome components with spatio-temporal precision and perform a spatial analysis of transcriptomes and proteomes in neighboring cells. With loss-of-function approaches and pathway activity reporters, we will ii. define the ‘sensome’ and the activity of inflammasomes in different areas of the epidermis. Using mouse models, we will iii. evaluate how spatial inflammasome activity drives skin inflammation. Through iv. AI-driven deep visual proteomics combined with an analysis of inflammasome activity, we will discover spatial in-flammasome activation and its effects in inflammatory skin disorders.
A precise understanding of spatio-temporal inflammasome signaling in the skin will be critical for se-lecting therapeutic targets acting as upstream drivers of prevalent diseases with high unmet needs.
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 biochemistry biomolecules proteins proteomics
- natural sciences biological sciences genetics RNA transcriptomes
- natural sciences biological sciences genetics mutation
- engineering and technology electrical engineering, electronic engineering, information engineering electronic engineering sensors
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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)
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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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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.
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Call for proposal
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(opens in new window) ERC-2022-ADG
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10117 Berlin
Germany
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