Objective
In a functional immune system, T cells serve as potent immunologic weapons, attacking foreign invaders, while tolerating the body’s own components. Unfortunately, these beneficial weapons can occasionally turn against self and attack the body’s own organs, resulting in autoimmunity. One of the most common reasons for this phenomenon is that the body fails to properly educate T cells on how to distinguish between self and non-self (foreign invader). These mis-educated cells then remain in the body where they can potentially cause autoimmunity by attacking its own organs. Recently a rare cell population of the thymic stroma, called the medullary epithelial cells (MECs), was shown to play a very fundamental role in this process. Namely, these cells have the amazing capacity to express essentially all body antigens, and in particular those, whose expression was previously thought to be restricted only to peripheral organs (e.g. pancreas). Hence, expression and a subsequent presentation of these peripheral-tissue-antigens (PTAs) to the differentiating thymocytes help to purge self-reactive T cells that could potentially cause autoimmunity. Many of these ectopic transcripts are regulated by the product of a single gene, the Autoimmune regulator (Aire), as mice with a mutation in this locus express only a fraction of the PTA repertoire and develop a multiorgan autoimmunity. Recently, we provided very significant insights into the Aire’s mode of action, by identification of its molecular partners. The research proposed herein is a direct continuation of these groundbreaking findings and specifically focuses on one of the most important and promising Aire-interacting partners – Topoisomerase 2a (TOP2a). The major objectives are to verify TOP2a significance under in vivo conditions, further delineate its mode of action, as well as to test whether its specific modulator – Etoposide could revert the onset of autoimmunity in Aire-deficient animals.
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.
- medical and health sciences basic medicine immunology
- natural sciences biological sciences genetics mutation
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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.
Topic(s)
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.
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.
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.
FP7-PEOPLE-2010-RG
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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.
Coordinator
7610001 Rehovot
Israel
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.