Laboratory Angelika Rambold
Eukaryotic cells are defined by numerous membrane-bound organelles, necessary to enable and compartmentalize specialized biochemical reactions inside a cell. The biogenesis, dynamics and activity of each individual organelle systems are tightly controlled, and alterations in some of these processes have been linked to various diseases, including several immune disorders. Mitochondrial defects cause altered immune cell homeostasis and lead to severe combined immunodeficiencies (SCID). Gene polymorphisms, which cause impaired autophagosome function, underlie Crohn’s disease and systemic lupus erythematosus. Functional imbalances of lysosomes and lysosome-related organelles can manifest in multiple immunodeficiencies, including the Chediak Higashi Syndrome, Gaucher diseases or α-mannosidosis.
Recent studies in non-immune cells have highlighted that organelles do not act as separate entities, but work as functionally interconnected networks. Lysosomes, autophagosomes, lipid droplets, peroxisomes and mitochondria synergize their dynamics and form selective interactions to direct the efficient exchange of lipids, amino acids or sugars. Communication between organelles can also take place without physical contact by exchanging bioactive molecules, such as peptides or ATP, and transcription factors. However, the functional significance of such organelle networks in immune cells has not yet been investigated.
Our research focuses on how individual organelles, inter-organelle communication and functional organelle networks regulate the activation of different immune cell types and contribute to organelle-related immune disorders. We investigate how organelles use dynamic changes in their morphology, shape, position and interaction to modulate spreading effects to other organelle systems and how this impacts immune cell function.
To gain an in-depth insight into how organelle dynamics and the organelle network infrastructure dictate immune function in a spatiotemporal manner, we employ state-of-the-art high-resolution microscopy and advanced live cell imaging techniques in combination with metabolic analysis and transcriptome profiling. Integrated into the Center for Chronic Immunodeficiency (CCI), we have a particular emphasis on cellular models of organelle-related primary immune disorders, with the aim to extend our studies to human patient material.