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Content archived on 2024-06-18

Molecular mechanisms of pediatric immunodeficiency syndromes affecting natural killer cell cytotoxicity

Objective

The pediatric immunodeficiency syndromes familial haemophagocytic lymphohistiocytosis types 3 (FHL3) and 4 (FHL4), and Griscelli syndrome type 2 (GS2) are associated with loss-of-function of Munc13-4, syntaxin 11 (Stx11) and Rab27a, respectively. These proteins are members of families of membrane fusion-regulating proteins, but the precise molecular role of these proteins in granule release is incompletely understood. All of these mutations result in a loss of cytotoxic function by NK cells and cytotoxic CD8+ T lymphocytes, resulting in a life-threatening sepsis-like condition. This project proposes to define the precise molecular role of these known regulators of NK cell granule exocytosis. In addition, other proteins will be screened for a role in granule release. These additional regulators may have mutations in the many patients with immunodeficiencies of no known genetic basis. In order to define the role of individual proteins in the granule release process, a detailed map of the sub-cellular events leading to granule exocytosis will be defined. The movement of proteins and organelles prior to fusion of granules with the cell surface is more complex than previously thought, and remains controversial. Thus, this project aims to increase understanding of the molecular mechanisms of lymphocyte cytotoxicity, in addition to broadening the spectrum of immunodeficiency syndromes and improving the clinical diagnosis and treatment of immunodeficiencies.

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-2009-IIF
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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-IIF - International Incoming Fellowships (IIF)

Coordinator

KAROLINSKA INSTITUTET
EU contribution
€ 181 669,40
Address
NOBELS VAG 5
171 77 STOCKHOLM
Sweden

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Region
Östra Sverige Stockholm Stockholms län
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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