dr. Marcel Bühler (PhD)

Organs and tissues, both in healthy and diseased conditions, are made up of a plethora of different cell types, each carrying out very specific tasks to maintain tissue function. In order to understand individual cell functions as part of this complex microenvironment, various single-cell analysis methods have been developed throughout the last decade. Although cell function is the ultimate result of coordinated protein activities, the vast majority of single-cell technologies are based on RNA-sequencing workflows. Such approaches have several inherent limitations:

• On a global scale, mRNA and protein abundances are poorly correlated and mRNA abundance measurements do not reliably reflect corresponding protein activities;

• The relatively low copy numbers of mRNA molecules result in counting noise, thus limiting the quantitative accuracy of RNA-seq measurements. This is particularly problematic for low-abundance transcripts.

• RNA-based approaches cannot account for post-translational regulation.

Recent advances in sample preparation and instrumentation have placed mass spectrometry-based single-cell proteomics (SCP) as a viable complementary tool for untargeted single-cell analysis, regularly quantifying around 2000 proteins per cell. Based on the cellenONE single-cell isolation platform installed in June 2023, the Gevaert lab is now establishing single-cell proteomics workflows for various applications in health sciences and basic research.
Despite constant improvements in (targeted) cancer therapies, many patients eventually develop treatment-resistant relapses. Interestingly, many of these recurrent tumors are not accompanied with distinct genetic or transcriptomic changes, a situation referred to as ‘non-genetic resistance’. Using our state-of-the-art instrumentation, we are developing SCP methods to dissect the proteomic changes associated with treatment resistance, with a main focus on melanoma and lung cancer (drs. Emin Araftpoor).
 

• 01/2023: PhD in Cancer Biology, University of Zurich, Zurich, Switzerland. Dissertation Title: ‘Longitudinal Characterization of the Glioblastoma Proteome Using PCT-SWATH Mass Spectrometry’
• 12/18: Master of Science in Biology (Major Biochemistry), Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland. Master Thesis Title: ‘Characterization of Epigenetic Inhibitors by Complementary Phenotypic Analysis and Histone Epi-Proteomics’
• 09/16: Bachelor of Science in Biology, Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland

Meetings/conferences:
PrIOMiC-OncoPoint symposium 2023, Technology Pitch: ‘Tackling Single Cell Proteomes: New Opportunities at CRIG’
 

• ‘Quantitative proteomic landscapes of primary and recurrent glioblastoma reveal a protumorigeneic role for FBXO2-dependent glioma-microenvironment interactions’. Neuro-Oncology, 2023. (PMID: 35802605)
• ‘Targeted delivery of tumor necrosis factor in combination with CCNU induces a T cell-dependent regression of glioblastoma’. Science Translational Medicine, 2023. (PMID: 37224228)
• ‘High-throughput identification of repurposable neuroactive drugs with potent anti-glioblastoma activity’. Nature Medicine, 2024. (PMID: 39304781) 
   

• Lab address: Gevaert Lab, VIB-UGent Center for Medical Biotechnology, Technologiepark-Zwijnaarde 75, 9052 Zwijnaarde
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• Marcel Bühler is involved in Single-Cell Network Ghent (SING)
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• Marcel Bühler provides Single-cell proteomics workflows (under development), available through collaborations with interested research groups
• Marcel Bühler is interested to receive invitations for presentations or talks