Objective
Modulating immune responses by shifting the balance of effector versus regulatory/memory T cells has significant potential as therapy for various autoimmune diseases and preventing organ transplant rejection. The mammalian Target Of Rapamycin Complex 1 (mTORC1) has diverse effects in T cells and can function to direct T cell fate. Direct mTORC1 inhibition provides potent immunosuppression but is associated with significant toxicity. Dissecting the mechanisms that account for the multiple mTORC1 effects on T cell differentiation is required to develop targeted therapies that provide desirable immunomodulatory effects without the toxicity associated with rapamycin treatment.
The function of activated T cells is closely linked to their elevated metabolic state. Thus, inhibition of T cell metabolism via disruption of glucose metabolism or amino acid availability can alter T cell function. mTORC1 activity is acutely sensitive to the metabolic cues and has established roles in regulating cellular metabolism in other systems, through the control of Hypoxia Inducible Factor 1α (HIF1α) and Sterol Response Element Binding Protein 1c (Srebp1c) transcriptional activity. Based on the hypothesis that mTORC1 integrates the control of T cell metabolism and differentiation via common pathways, our data reveals a dual role for mTORC1/HIF1α in controlling glucose metabolism and CD8 T cell function. Lipid metabolism, controlled by mTORC1/Srebp1c in other cellular systems, has also been linked to T cell differentiation. Preliminary results demonstrate that activated T cells contain active mTORC1/Srebp1c signaling and suggest mTORC1 activity controls Srebp1c target genes, supporting a potential role for mTORC1/Srebp1c in the control of T cell function. This project aims to characterize the role for mTORC1/Srebp1c in the activation, differentiation and function of T lymphocytes using complementary pharmacological and genetic approaches and using state of the art in vivo technologies.
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
- natural sciences biological sciences cell biology cell metabolism
- natural sciences biological sciences biochemistry biomolecules lipids
- medical and health sciences basic medicine immunology autoimmune diseases
- natural sciences chemical sciences organic chemistry amines
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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
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.