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Content archived on 2024-06-18

Mechanisms of immune surveillance of senescent cells

Objective

Cellular senescence, a stable form of cell cycle arrest, is a mechanism limiting the proliferative potential of cells. Recent studies demonstrate that cellular senescence imposes a potent barrier to tumorigenesis and contributes to the cytotoxicity of certain anticancer agents. In addition to sites of persistent damage and precancerous lesions, senescent cells have also been observed in tissues of aged individuals and can contribute to decline of tissue function with age. Therefore, mechanisms responsible for control over presence of senescent cells play central role in cancer prevention and aging. In my post-doctoral training I was first to demonstrate that cellular senescence protects against liver fibrosis, and that senescent cells can be cleared by the innate immune system to insure return to the pre-damage state. Components of the innate immune system, macrophages and NK cells were also demonstrated to clear senescent cell from tumors. However, molecular mechanisms of the recognition and the killing of senescent cells remain to be understood. Therefore, I propose to study contribution of NK cells and macrophages to recognition and elimination of senescent cells. Molecular mechanisms responsible for these interactions will be studied using engineered cell lines were senescence can be induced. Elaborate short hairpin RNA techniques will allow discovery of genes in senescent cells that are responsible for signaling to immune cells from one side, and from the other side identification of molecules in immune cells that can contribute to senescent cell elimination. Uncovering the mechanisms of interaction of senescent cells with the immune system will reveal the role of these interactions in diseases and aging and might ultimately lead to development of novel treatments.

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

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FP7-PEOPLE-2009-RG
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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-IRG - International Re-integration Grants (IRG)

Coordinator

WEIZMANN INSTITUTE OF SCIENCE
EU contribution
€ 100 000,00
Address
HERZL STREET 234
7610001 Rehovot
Israel

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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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