瑞士诺华生物医学研究所免疫学博士后职位

Candidate profile: Strong background in immunology. Experience in complement, Fc receptor or apoptosis biology and preclinical models of autoimmune disease is preferred.

The project will investigate the signals and mechanisms responsible for uptake of apoptotic cells by phagocytes in inflammatory diseases, with the aim of identifying novel therapeutic concepts to restore homeostatic apoptosis and thereby re-establish tolerance to self.

Background:
As part of normal tissue homeostasis in a living organism, billions of cells undergo apoptosis every day and need to be cleared. Removal of apoptotic cells happens in an immunologically silent, non-phlogistic way and is key for the maintenance of self-tolerance. The process of apoptosis is characterized by the breakdown of intracellular components such as nucleotides, DNA and intracellular proteins, which otherwise would act as “danger signals”. In addition, apoptotic cells change the decoration of their cell membrane to be recognized, engulfed, and cleared by phagocytes. Decoration of apoptotic cell surfaces is not only modulated by cell-intrinsic mechanisms that induce expression of cell surface molecules, but also involves opsonization with antibodies and complement. Defects in this pathway (e.g., complement deficiencies) result in failure of apoptotic cell clearance and severe autoimmune syndromes in humans. In these patients, chronic inflammation may be driven by insufficient/aberrant clearance of apoptotic cells and/or by phenotypic changes of phagocytic immune cells. During chronic inflammation, danger signals from activated immune cells and necrotic cells may override the non-phlogistic capacities of apoptotic signals.