Dalle Pezze et al. 2016; Artwork by Ineke Buist
Lab for Metabolic Signaling
hosted by the European Medical School (EMS) Oldenburg - Groningen
The Lab for Metabolic Signaling studies the control of metabolic homeostasis by kinase networks centred on the mammalian target of rapamycin (mTOR). We adopt cell biology, biochemistry, proteomics, and systems approaches.
mTOR is a central controller of metabolism and ageing. mTOR is dysregulated in most cancers as well as in metabolic and neurodegenerative and congenital disorders, and is therefore of major biomedical interest as a drug target and biomarker. The kinase mTOR is at the center of a large signaling network and exists in two structurally and functionally distinct multiprotein complexes, named mTOR complex 1 (mTORC1) and mTORC2. mTORC1, in response to growth factors (insulin), nutrients (amino acids), energy (ATP), and stress (e.g., reactive oxygen species) controls growth related processes such as translation, ribosome biogenesis, and autophagy. mTORC2 is a central metabolic regulator as well which is involved in lipid and glucose homeostasis.
mTOR, via a complex kinase network, regulates virtually all anabolic processes at the cellular and organismal level. But how are specific metabolic responses to distinct metabolic inputs achieved? We hypothesize that different molecular networks transduce specific metabolic stimuli and mTOR-dependent metabolic responses. Hence, we aim to identify novel mTOR network components and delineate their interconnection in relation to different metabolic inputs and outputs. To this end, our lab analyzes the mTOR interactome and phosphotargets using proteomic and biochemical methods (Schwarz et al. 2015). To deal with mTOR network complexity, systems biology approaches are adopted to unravel novel regulatory connections governing mTOR’s activity and outputs (Dalle Pezze 2016; Sonntag et al 2012; Dalle Pezze 2012). We functionally characterize novel mTOR regulators by cell biological approaches. For example, we investigate regulators which control mTOR activity and cellular survival under stress (Heberle et al. 2015; Thedieck et al. 2013), and we unravel mTOR crosstalk with other signaling networks such as TGFbeta (Thien et al. 2015) and autophagy (Ruf et al. 2017).