Objective
There is growing evidence that molecules classically allocated to nervous system function, such as the neurotrophic factors, are produced by lymphocytes and can also regulate their function. The neurotrophic family includes the GDNF ligands (GFLs), which signal through the RET tyrosine kinase receptor. In humans, mutations of the proto-oncogene Ret have been linked to different diseases, such as cancer and Hirschsprung’s disease. Interestingly, RET expression has been reported in lymphocytes but its functional significance is unclear. We propose to use combined genetic, cellular, and molecular approaches in order to determine, quantify and manipulate the function of RET and GFLs during haematopoiesis and lymphocyte differentiation. In order to achieve this, we will analyse the patterns of RET and GFL expression during haematopoiesis, and in mature lymphocyte sub-sets. By using this strategy we aim to identify differentiation stages where the Ret exerts its role. We then plan to assess the functions of RET and candidate GFLs by studying the impact of Ret and GFL gene ablation. To achieve this, we will study lymphoid cells at different stages of differentiation from mice deficient for Ret or GFLs, and determine the role that these molecules play in key cellular and molecular events during haematopoiesis and immune responses. Since RET is likely to exert its function at various differentiation steps, we plan to use genetically modified mice allowing the conditional deletion of Ret. As a complementary approach, we will generate mice over-expressing RET or constitutively activated RET in a tissue-specific manner, thus mimicking activating mutations of RET associated with cancer. We believe our work, apart from its novelty in the field of immunology, will have a broader impact in other disciplines. Indeed, mechanisms historically ascribed to a specific tissue may be used more generally in order to orchestrate the function and communication among different systems.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences neurobiology
- medical and health sciences basic medicine immunology
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine oncology
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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.
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.
ERC-2007-StG
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.
Host institution
1649 028 Lisboa
Portugal
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.