MS instrument for high resolution and high speed targeted and non-targeted metabolomics

• Subject Area: Basic Research in Biology and Medicine
• Term: Funded in 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 554078182

In the frame of Prof. Thedieck’s recruitment as Department Head for Metabolism, Senescence and Autophagy at the Research Center One Health Ruhr (RCOH) and University Hospital Essen, we apply in two linked proposals for two high resolution mass spectrometers for integrated proteo-metabolomics. (1) One instrument is for quantitative proteomics and PTM analysis with ultrahigh resolution and sensitivity in enriched samples, small cell populations and single cells. (2) The other instrument enables ultra-fast applications for targeted metabolite quantification and non-targeted metabolomics. Our projects intertwine MS-based proteomics and metabolomics to gain an integrated understanding of metabolic signaling. Our research centers on the kinase network converging on mTOR (mechanistic target of rapamycin), a central controller of cell growth and metabolism. mTOR drives age-related diseases, including cancer, neurodegeneration and metabolic disorders, and rare congenital conditions such as Tuberous Sclerosis Complex (TSC) and other mTORopathies. We study metabolic regulation through mTOR by means of biochemistry, proteomics, metabolomics, cell biology and systems approaches. Interactome studies reveal new mTOR regulators, phosphoproteomics discover new downstream effectors, and interplay with other signaling routes comprises protein methylation or acetylation. Our metabolomics studies encompass mTOR-driven metabolic processes including amino acid and central metabolism. In patient-centered studies, we investigate proteome and metabolic alterations in cell and animal models and patient cohorts. A major focus, funded by an ERC Advanced Grant, is the regulation of the mTOR network by stress granule proteins, stress-induced protein-RNA complexes, under non-stress metabolic conditions. Funded by the RCOH and EU projects, we investigate interference of environmental metabolic disruptors with mTOR signaling and cancer therapy. This proposal is for instrument (2), a mass spectrometer for high resolution and high speed targeted and non-targeted metabolomics. It needs to meet the following criteria: high resolution, accuracy and flexibility for ultra-fast targeted metabolite quantification and non-targeted metabolomics in biological samples; ion mobility spectrometry as an additional separation dimension; high scan speed and flow rate and low maintenance and downtime for high throughput clinical metabolomics and proteomics; targeted proteomics for pathway panels for mTOR, autophagy and the lyso-proteome. LC-MS/MS applications require a UPLC system, an ion chromatography (IC) for polar phosphorylated metabolites, a robust nano-source and a nano-UPLC with low maintenance and downtime for high throughput proteomics. Work stations and MS analysis software enable metabolite and proteome data processing. This infrastructure is a mandatory prerequisite for our research, and is currently not available at the University Hospital Essen.

• DFG Programme: Major Research Instrumentation
• Major Instrumentation: MS-Instrument für hochauflösende und ultraschnelle gezielte und nicht gezielte Metabolomforschung
• Instrumentation Group: 1700 Massenspektrometer
• Applicant Institution: Universität Duisburg-Essen
• Leader: Professorin Dr. Kathrin Thedieck