- Cell death and senescence
- Intracellular compartments and transport
- Molecular and cell biology not elsewhere classified
Medical and health sciences
- Innate immunity
- Cell death
- Membrane structure and transport
On a daily basis, billions of cells undergo turnover in essentially all tissues in the human body as part of the normal process of development, growth and routine healthy living. The removal of the dead cells (i.e. efferocytosis) is crucial to avoid inflammatory insults and auto-immune diseases, and is carried out by specialized 'eating' cells (i.e. phagocytes) that are part of the immune system. These phagocytes are specialized in sensing, recognizing, ingesting, and digesting the corpses, and proper removal of dying cells is critical for normal healthy living. Recently, our laboratory has identified a new set of genes (belonging to the solute carrier family, SLC) that are regulated during efferocytosis and control how a phagocyte eats dying cells and how this leads to reducing inflammation. One of the main goals of this research proposal is to define the function of SLCs acting as direct boosts or brakes on efferocytosis. We will make use of a newly developed technique to edit the genome, and then evaluate the roles in efferocytosis for the SLCs ( ˜400 members) that transport different metabolites and ions in and out of cells. Further, we will evaluate the role of a specific family of SLCs involved in transport of zinc into phagocytes and its relevance in specific disease models. We expect our study to provide new knowledge on the function of SLCs in efferocytosis and potential points of therapeutic intervention to modulate efferocytosis in specific inflammatory diseases.