Cellular Proteomics and Metabolic Signaling

Cellular organelles provide functionally distinctive compartments for diverse biochemical reactions and are highly dynamic structures that adapt to environmental challenges. These adjustments can take many forms, including changes of protein and lipid composition, biochemical activities, organelle morphology and distribution or interactions with other organelles. Nutrient availability is one of the environmental factors with the highest fluctuations. Cells cope well with abruptly changing nutrient levels that organisms are exposed to each day (such as fasting and feeding cycles), but chronic overexposure to nutrients represents a severe form of environmental stress and leads to obesity and associated diseases. How cells change their organization during the development of metabolic diseases and how this is controlled by signaling pathways in different organs and tissues is still poorly understood but the basis for the identification of novel pharmacological targets.



Our goal is to combine systems biology approaches, especially proteomic and phosphoproteomic workflows with cell biological methods such as super-resolution microscopy to characterize cellular changes underlying the development of metabolic diseases and to identify proteins and signaling pathways that control those changes. As an example, we are following up on previous findings how cellular lipid accumulation in hepatic steatosis changes the contacts between organelles and influences the secretory pathway. In addition, we are using novel phosphoproteomic workflows to identify new players in leptin signaling and leptin resistance.