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Content archived on 2024-06-18

Memory control; Molecular mechanisms underlying the scope of immunological memory

Objective

T cell mediated immunity protects us against pathogens and cancer. The naïve T cell pool consists of millions of clones, each one unique based on its T cell receptor (TCR). Upon infection, only a few of these clones are recruited to generate antigen-specific memory. Selection of memory clones is a trade-off between specificity and diversity; too much specificity restricts antigen-recognition, which precludes responsiveness against pathogens with small mutations. Too much diversity impairs efficiency of recall responses. Mechanisms controlling memory diversity are largely unknown. In this project I will identify and characterize the role of molecules that control memory cell diversity to answer the question whether optimal diversity is inherently present in the immune system or may be adjusted to benefit vaccine strategies.
I will set up novel in vitro models for the generation of memory cells and analysis of the role of TCR-affinity on memory cell formation using murine cells. With this platform, I will perform high-throughput screening for the identification of potential target genes involved in the regulation of TCR affinity-dependent memory cell formation. In addition, a new mouse model will be generated for the specific deletion of genes in memory T cells. This system will be used to verify the in vivo effects of candidate genes on memory cell diversity. Finally, I will demonstrate the clinical relevance of our murine findings by corroborating our observations with novel human cell culture systems.
In summary, I propose to investigate a currently underappreciated aspect of immunity. Our technological and scientific innovations ensure rapid generation of new, relevant and high-impact data. Elucidation of the mechanisms that mediate memory cell diversity are of high relevance, as it allows a more rational design of vaccines that require broad neutralizing (e.g. against influenza or HIV), or highly specific (e.g. against cancer) responses.

Fields of science (EuroSciVoc)

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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.

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

FP7-PEOPLE-2013-CIG
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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.

MC-CIG - Support for training and career development of researcher (CIG)

Coordinator

ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM
EU contribution
€ 75 000,00
Address
MEIBERGDREEF 15
1105AZ Amsterdam
Netherlands

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Region
West-Nederland Noord-Holland Groot-Amsterdam
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

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