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Content archived on 2024-06-18

Molecular and cellular mechanisms in phagocytosis of apoptotic cells

Objective

The proper elimination of unwanted or aberrant cells through apoptosis and subsequent phagocytosis plays a crucial role in metazoan development and tissue homeostasis. Inefficient or defective removal of apoptotic cells leads to inflammation and autoimmune diseases. Given that in vertebrates phagocytosis is a complex and highly redundant process, we are using the Drosophila model, which permits comprehensive in vivo studies and provides complement to medical and applied approaches in the field. We previously identified and characterized a novel phagocytic receptor, named Six Microns Under (Simu), which strongly binds to apoptotic cells and is required for their recognition and engulfment by glia in the nervous system and by macrophages elsewhere. However, the mode of SIMU’s action is, like of many other phagocytic receptors, still unknown. The goal of the proposed research is to elucidate the molecular and cellular mechanisms underlying the recognition of apoptotic cells by phagocytes and subsequent signaling for engulfment. We will further characterize SIMU’s function by finding its physical interaction partners, both its ligand on the apoptotic cell and its presumptive co-receptor on the phagocyte. Then we will focus on the mechanisms of their action and interaction. Based on two independent genetic screens we will test candidates with presumed or known function in phagocytosis in order to explore novel pathways in apoptotic cell clearance. By studying factors involved in different pathways we will address the redundancy issue in the phagocytosis process. Accomplishment of our research goal will shed light on the general mechanisms of receptor binding, clustering and signaling in phagocytosis, which will provide novel and important insight into a key biological process with potential translation into equivalent studies in mammalian systems and medical applications in the diagnosis and treatment of human diseases.

Fields of science (EuroSciVoc)

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Topic(s)

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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

TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY
EU contribution
€ 100 000,00
Address
SENATE BUILDING TECHNION CITY
32000 Haifa
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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