Lab for Metabolic Signaling
The comic illustration shows G3BP (G) tethering the TSC complex to a lysosome, thereby preventing the MTOR (aka Thor) signaling protein from becoming active. © Christoph Luchs
Cell. 2021 Feb 4;184(3):655-674.e27. doi: 10.1016/j.cell.2020.12.024
The Lab for Metabolic Signaling studies the control of metabolic homeostasis through kinase signaling networks converging on the metabolic master regulator mTOR (mammalian / mechanistic target of rapamycin) in health and disease. We adopt biochemistry, cell biology, proteomics, metabolomics and systems modelling approaches.
mTOR is a central controller of metabolism and ageing. mTOR is dysregulated in most cancers as well as in metabolic, neurodegenerative and congenital disorders, and is therefore of major biomedical interest as a drug target and biomarker. The protein kinase mTOR is at the center of a complex signaling and metabolic network, and exists in two structurally and functionally distinct multiprotein complexes, mTOR complex 1 (mTORC1) and mTORC2. In response to growth factors, nutrients, energy and stress, mTORC1 enhances anabolic processes such as translation, and represses catabolic processes such as autophagy. mTORC2 is a central metabolic regulator as well which is for instance involved in lipid and glucose homeostasis.
mTOR controls virtually all metabolic processes at the cellular and organismal level. But how are specific metabolic responses to distinct metabolic inputs achieved? The complex wiring of signaling networks allows to link distinct metabolic stimuli with specific metabolic responses. Our lab aims to identify novel network components and to delineate their interconnection in relation to mTOR’s metabolic inputs and outputs. To this end, we analyze its interactome and ancillary signaling and metabolic networks by ultrahigh resolution mass spectrometry, including targeted, shotgun and fluxomic proteomic and metabolomic methods. To deal with mTOR network complexity, we adopt systems approaches to unravel novel regulatory connections. We functionally characterize novel regulators and effectors by means of biochemistry and cell biology in in vitro and in vivo models as well as in human
Our excellence is highlighted by prestigous National and European grants and awards including the ERC Advanced Grant BEYOND STRESS
Located in the Department for “Metabolism, Senescence and Autophagy” at the Research Center One Health Ruhr, we focus on metabolic signal transduction. Of particular interest is the interplay of oncogenic signalling cascades with tumour metabolism for the development of new predictive markers and therapeutic targets in preclinical models and clinical studies.
Our method portfolio focuses on the biochemical and cell biological analysis of new mechanisms and the systems analysis of signalling and metabolic networks. Quantitative MS analysis of the proteome and metabolome and systems modelling go hand in hand. The department offers excellent instrumentation with the latest equipment technology for molecular & cell biology, biochemistry and MS-based proteo-metabolomics.
The newly founded Research Centre One Health Ruhr – from Molecules to Systems of the Universities of Duisburg-Essen, Dortmund and Bochum focuses on research into the fundamental mechanisms of health and disease, from the molecular level to higher-level systems. The ecosystem is the context in which we consider the complex interactions between environmental health, animal health and human health in the sense of the “One Health” concept. The “Metabolism, Senescence and Autophagy” department is particularly concerned with the influence of metabolic disruptors on oncogenic mechanisms and therapy response.
The Faculty of Medicine enjoys an excellent reputation – in the clinical and translational fields as well as in basic research. The key research areas “Oncology”, “Cardiovascular Diseases”, “Immunology and Infectiology”, “Translational Neuro- and Behavioural Sciences” and “Transplantation” are internationally established. We offer an excellent scientific environment and attractive opportunities for collaboration with renowned international, national and regional partners. As a site of the German Consortium for Translational Cancer Research (DKTK) and the National Centre for Tumour Research (NCT), we are embedded in a network of excellent partners in cancer research.