In synthetic chemistry, a few reactants are mixed with a solvent, placed in a vessel and allowed to react for a specified time under defined conditions. Spectroscopic methods are then used for the analysis of the resulting mixture as a whole, or of individual compounds upon isolation if more detailed information is required. Proteomics – the study of the proteins present in a cell, tissue, or organism – follows the same general concept. It has to operate on a very different scale, however. Specifically, it needs to account for the potential presence of millions of compounds in the sample, deal with the dramatically increased number of possibilities of reactions, or interactions, between these compounds, and keep track of any quantitative changes they may undergo. Nonetheless, basic chemical principles still apply, and spectroscopic methods can still be used for sample analysis. Due to the vastly increased numbers of compounds, an analytical technique capable of handling complex mixtures and distinguishing compounds by inherent molecular and submolecular characteristics would be highly preferential for proteome research.
Modern mass spectrometry has proved to best fit that description. Invented more than a century ago by Sir Joseph John Thomson (1906 Nobel prize in Physics) – mass spectrometry has traditionally been used to study the composition of atoms and small molecules. The introduction of the soft ionization techniques electrospray and laser desorption (2002 Nobel prices in Chemistry awarded to John B. Fenn and Koichi Tanaka) in the late 1980’s enabled the direct analysis of biological macromolecules such as DNA, RNA, and proteins. Advances in MS instrumentation, DNA sequencing, and computer technology now make possible the analysis of increasingly complex mixtures, establishing mass spectrometry as an essential analytical technique in proteomics.
In our research, we heavily rely on mass spectrometry to study cellular reactions and their products, to identify the proteins present in human cells, their interactions, and any modifications they may undergo. Comparing this information across multiple cellular states allows us to gain a better understanding of how the system is balanced, and how it responds to changes. We can determine, for example, how certain blood cells receive and process external signals and how specific drugs influence these mechanisms. To accomplish this, we utilize mass spectrometry to characterize the products of chemical reactions such as cross-linking of proteins in live cells and stable isotope labeling of proteins or peptides, identify drug-induced protein modifications and other cellular responses, and to trace them with high specificity and sensitivity in targeted experiments across multiple states. Step by step, this provides us with a detailed picture of the various cellular processes and their underlying biochemical mechanisms. For details on current projects, please click on "Biomedical Research Centre" above.