THE IMMUNE SELF-ASSOCIATED STORAGE ORGANELLE (SASO)

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PROJECT SUMMARY This study investigates how the body maintains a memory of ‘Self’. When facing foreign organisms and cancer, this self-knowledge is thought to be critical, serving to educate the immune system to limit autoimmunity and conversely license reactivity to things that are ‘Foreign’. The core of the study focuses on a newly-discovered organelle, found within macrophages and some dendritic cells which we call the Self-Associated Storage Organelle or SASO for short. We believe that the SASO is critical to ‘hold’ our self-identity and subsequently educate the rest of our immune system and it appears to come from a stealthy and subtle form of ‘cell nibbling’.Our proposal is unique in applying cutting technologies—lattice-light sheet imaging, vesicle flow, Mass- spectrometry and Electron Microscopy—together with conventional cellular immunoassay methods and genetic screens, to understand how this newly described component of the immune system works as well as how we can harness it to improve health. The resultant discoveries will be formative for designing new ways to boost anti-tumor immunity, to minimize autoimmunity and to broadly regulate which components of our bodies are seen as ‘Self’.