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 samples.