AC REMOVAL MECHANISM (249084)

  https://cordis.europa.eu/project/id/249084

  FP7 (2007-2013)

  Molecular and cellular mechanisms in phagocytosis of apoptotic cells

  Marie Curie Action: "Reintegration Grants" (FP7-PEOPLE-2009-RG)

  neurobiology  ·  autoimmune diseases  ·  homeostasis

  2009-11-01 Start Date (YY-MM-DD)

  2013-10-31 End Date (YY-MM-DD)

  € 100,000 Total Cost

  Description

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.

  Complicit Organisations

1 Israeli organisation participates in AC REMOVAL MECHANISM.