Project description
A new frontier in inflammation research
Inflammation is a defensive reaction of the organism due to the detection of foreign infectious agents or in the effect of tissue damage. However, some severe diseases like neurodegeneration, atherosclerosis, diabetes and cancer are linked to chronic, long-term inflammation that is stress-induced and occurs as a response to cell stress provoked by perturbations of normal physiology. Unfortunately, crucial sensors and effectors of stress-induced inflammation remain a mystery. The EU-funded DESTRESS project will explore the role and behaviour of the so-called death receptors, members of the tumour necrosis factor receptor family, as integrators of stress-induced inflammation to unveil the composition of their signalling complexes, shift research and enable effective treatment of numerous diseases associated with cell stress.
Objective
Inflammation is initiated in response to the detection of foreign entities, called PAMPs derived from infectious agents, or due to the release of intracellular contents, called DAMPs, due to serious tissue damage (i.e. necrosis). However, inflammation can also be initiated in response to Cell Stress (e.g. ER stress, cytoplasmic stress, mitochondrial stress) resulting from perturbations in normal physiology, but how cellular stress is converted to inflammatory outputs is very poorly understood. Many diseases are associated with chronic long-term inflammation (e.g. cancer, obesity, neurodegeneration, diabetes), which is a compounding factor in these conditions that can accelerate disease progression, but the inflammation seen in these conditions does not have an obvious infectious (PAMP) or acute injury (DAMP) cause. Instead, these diseases are frequently associated with persistent cell/tissue stress (e.g. due to misfolded proteins, elevated dietary fats, or metabolic stress) arising from persistent ER or cytoplasmic stress, that is likely to serve as a key driver of inflammation in these settings. However, the key sensors and effectors of stress-induced inflammation remain enigmatic.
Based on our recent observations, I wish to explore the hypothesis that members of the 'Death Receptor' subset of the TNF receptor family serve as stress-associated molecular patterns (SAMPs), becoming upregulated and/or activated in response to divergent forms of ER and cytoplasmic stress, leading to inflammation. Here, we will explore the role of Death Receptors as putative SAMPs, how they are activated by stress, the composition of their stress-induced signaling complexes, and the potential to suppress stress-induced inflammation through targeting these receptors. Understanding how Cell Stress initiates inflammation will open up a new frontier in inflammation research and identify new molecular targets for the treatment of chronic inflammation associated with multiple diseases.
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 neurobiology
- medical and health sciences clinical medicine endocrinology diabetes
- medical and health sciences clinical medicine oncology
- medical and health sciences basic medicine physiology
- medical and health sciences health sciences nutrition obesity
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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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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
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
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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.
ERC-ADG - Advanced Grant
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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-2020-ADG
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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.
D02 CX56 Dublin
Ireland
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.