Proteomics Technology Development & Application
Co-workers: (currently based at Utrecht University) Alba Cristobal, Christian Frese, Fabio Marino, Lucrece Matheron, Nhat Verhage-Bui, Nadine Binai and Vincent Halim
Proteins are central to many essential molecular processes in living cells. They perform functions through interactions in a highly dynamic environment with each other and with other types of molecules including sugars, lipids and nucleic acids. In recent years, characterisation of proteins has accelerated dramatically, driven by the completion of many genomes and the constant evolution of mass spectrometry. The genome contains information relating to all possible proteins that can be present in the cell and thus this extractable data represents an invaluable repository of knowledge for protein identification. Equally significant was the realisation that mass spectrometry represents an almost ideal tool for protein sequencing. However, the composition of proteins present in a cell is only one determinant of function. Both protein expression levels and subtle biochemical changes to protein structure, in the form of post-translational modifications (PTM), dynamically influence cellular processes.
PTM of proteins is nature's way to regulate protein function, their interactions and sub-cellular localisation. Furthermore, proteins involved in regulation are becoming major drug targets for a wide variety of diseases. Therefore, the accurate measurement of protein expression and modification is essential to understanding the underlying biomolecular determinants of cellular signaling.
Currently, I am involved in:
- developing chromatographic techniques for application in a proteomics environment,
- enrichment of post translational modifications,
- characterization and exploitation of electron transfer dissociation for peptide sequencing,
- creation of facile chemical labeling based quantification and
- elucidation of (PTM based) signaling pathways through quantification.
- "Toward full peptide sequence coverage by dual fragmentation combining electron-transfer and higher-energy collision dissociation tandem mass spectrometry." Frese CK et al. Analytical Chemistry 2013 Nov 20;84(22):9668-73
- "Tumour suppressor RNF43 is a stem cell E3 ligase that induces endocytosis of Wnt receptors" Koo B-K et al. Nature 2012 30;488(7413):665-9
- "Highly sensitive proteome analysis of FACS-sorted adult colon stem cells." Di Palma S et al. Journal of Proteome Res. 2011 10(8):3814-9
- "Enhancing the identification of phosphopeptides from putative basophilic kinase substrates using Ti (IV) based IMAC enrichment." Zhou H et al. Molecular and Cellular Proteomics. 2011 10(10):M110.006452
- "Multiplex peptide stable isotope dimethyl labeling for quantitative proteomics." Boersema PJ et al. Nature Protocols 2009, 4(4), 484-94
- "Straightforward ladder sequencing of peptides by a combination of Lys-N proteolytic cleavage and electron transfer dissociation" Taouatas N et al. Nature Methods 2008, 5(5), 405-7
Graduate Student and Postdoctoral Positions: TBA