Objective
The immune system maintains a vast repertoire of lymphocytes waiting to respond to microbial invasion. These cells are kept in a quiescent state, characterized by arrest in G0 and a decrease in cell size and metabolic activity, until they are activated. Not long ago, quiescence was considered equivalent to “absence of activation”, namely a default state of the cell. Recently our discovery of a chemically induced mutation, elektra, enabled us to illustrate what happens when quiescence fails. Elektra mice showed an abnormally high frequency of T-cells in a semi-activated state and suffered from immunodeficiency. We ascribed the elektra phenotype to a mutation in Slfn2, a gene of previously unknown function, and concluded that SLFN2 plays an essential role in immune defense, where it operates to maintain quiescence in T-cells and monocytes. Moreover, our results demonstrate that quiescence programming must be actively maintained. However, lymphocyte quiescence is still poorly understood and the mechanism by which SLFN2 maintains it is also unknown. We now propose to use molecular approaches combined with unbiased forward genetic screening to elucidate mechanisms by which SLFN2 enforces T-cell quiescence. Specifically, we will: 1) identify SLFN2 binding partners and investigate the nature of the interactions; 2) elucidate key molecular processes in T-cells regulated by SLFN2 by a forward genetic screen. These findings will likely have relevance to other immune cell populations which are not T-cells and may also clarify the function of other members of the SLFN family. The identification of lymphocyte quiescence maintaining factors will integrate to understand how the immune system is able to defend the host while maintaining self tolerance and therefore have the potential to be exploited for therapeutic purposes in immune disorders, either by enhancing specific anti-pathogen/tumor immune responses or by suppressing overactive, self-directed responses.
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-2012-CIG
See other projects for this call
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.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
91904 JERUSALEM
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.