Mass spectrometry (MS) is the chief technology for proteome and metabolome analysis to examine proteins and metabolites that, in contrast to genes, are most directly linked with the regulation of cellular processes in any biological system. Although MS matured over the last decade, various challenges still need to be met for optimal and stable performance. This pertains to technical aspects for sample collection, sample preparation, peptide/metabolite separation, MS analysis, and bioinformatics that need to be seamlessly integrated for deployment in effective pipelines. In addition, these pipelines can be tailored in multiple ways, e.g. for optimized throughput, quantitative accuracy, or detection of posttranslational modifications, either in a global or targeted manner. To optimize these various facets specifically to establish mass spectrometry in systems medicine, SMART-CARE brings together teams of mass spectrometrists that represent broad expertise in proteomics and metabolomics at the Heidelberg medical campus.
The Klingmüller team in SMART-CARE has expertise in all aspects of quantitative and targeted proteomics, the analysis of phosphoprotein and mathematical modeling. The overarching goal of the Klingmüller group is to establish robust and standardized methods for the in-depth analysis of tissue and plasma samples from patients by mass spectrometry with a major focus on lung cancer. Of particular interest is the development of targeted proteomics for the absolute quantification of proteomic changes and the advancement of phosphoproteomics. These approaches together with mechanistic mathematical models allow to identify robust protein markers in blood plasma correlating with tumor recurrence and establish personalized models as decision tools for patient stratification.
Barbara Helm, Dario Frey, Piotr Zadora, Franziska Gödtel, Ursula Klingmüller (from left to right)
COS University Heidelberg
The Metabolomics Core Technology Platform (MCTP) is a DFG-registered core facility of the University of Heidelberg and part of the Centre for Organismal Studies (COS). Within SMART-CARE, the MCTP (Team Hell) provides high-quality, targeted metabolomic analyses utilizing state of the art methods and equipment to reliably discover and subsequently quantify potential biomarkers for the prediction of cancer recurrence.
The scientists of the MCTP follow a two-way approach to uncover potential biomarkers by utilizing robust and validated targeted LC-MS/MS based assays, and further, developing novel in-house methods based on the findings and the expertise of the clinical as well as global mass spectrometry teams.
Hagen Gegner, Nina Kunze-Rohrbach, Gernot Poschet (from left to right)
University Hospital Heidelberg / DKFZ
The Krijgsveld team in SMART-CARE has a broad expertise in all facets of quantitative proteomics, focusing on the development of novel methodologies for the preparation (SP3), measurement, and data analyses (IceR) of low-input specimens. To meet reproducibility and turnaround requirements, the Krijgsveld team developed an end-to-end solution for the automated processing of any sample type to MS-compatible peptides, including paraffin-embedded and formalin-fixed (FFPE) tissue, fresh-frozen (FF) tissue, and liquid biopsy material (blood plasma and serum). Built on a state-of-the-art infrastructure for MS-based proteomics, we aim to push the boundaries of robustness, reproducibility, and data completeness to enable translational proteomics in the context of stratification of tumor recurrence.
The Center for Mass Spectrometry and Optical Spectroscopy (CeMOS) in Mannheim co-develops translational technology platforms for industry and, increasingly, for clinics. As one of the leading Applied Science Centers (~75 third-party funded employees) it operates, among other things, the Rhine-Neckar Center for MS imaging and MS assays. CeMOS utilizes five state-of-the-art mass spectrometers for co-development of consumables, specialty chemicals, devices, processes, laboratory automation and IT solutions in MS and optical spectroscopy.
In SMART-CARE, CeMOS develops innovative automated workflows for miniaturized untargeted LC-MS/MS lipidomics/metabolomics analysis of cancer plasma and tissue samples for the discovery of biomarkers for the prediction of cancer recurrence. CeMOS works with SMART-CARE partners on robust quantification of the markers, on data integration and on modeling.