“Life essentially can be characterized as a sequence of actions triggered by signals. Peptides are carriers of those signals.”
– From the 2010 Annual report of Department of Biotechnology, TU Delft.
When Peter Verhaert became the new leader of the Analytical Biotechnology (ABT) group in 2005, his mission was to introduce a selection of the latest proteomics techniques to Delft. Proteomics, the large-scale study of proteins structure and function, would nicely complement research in other groups of the department. With the installation of state-of-the-art instrumentation – the ion trap-orbitrap hybrid mass spectrometer next to the quadrupole-TOF system – this has now been achieved. At the same time new research lines have been established, focussing on peptides and bio-imaging.
Proteins are the workhorses of biological processes. Performing virtually all essential actions in and around cells, they exist in an endless variety. Not surprisingly, the study of proteins has in recent years become a high-throughput endeavour, relying on technologies capable of identifying hundreds of proteins in a single experiment. In order to do so, the complex proteins are separated in multiple dimensions, broken up in smaller pieces, peptides, the unique masses of which are determined by mass spectrometry. Bioinformatics then helps to link the peptides to their protein identity.
“But peptides are more than just pieces of proteins,” says Verhaert. “Virtually all living systems release peptides for communication purposes. They can serve as signals.” By ‘listening’, peptidomics researchers can deduce information about the condition a living (i.e., signalling) organism is in. “The difference between healthy and cancerous cells can be established by identifying peptide signals. In a way they’re natural biomarkers.” ABT also studies the ‘language’ of human immune cells (a collaboration with the pharmaceutical industry) and that of microorganisms inside an industrial fermentation reactor, providing real-time, in-situ clues about the optimal processing conditions. A future challenge lies in using this language to have peptides trigger actions inside an organism. “Think of woundhealing peptides or peptides actively used to combat cancer or HIV.”
Mass spectrometry imaging
The experimental infrastructure of ABT consists of tools that have been developed at the group for many years (such as microfluidics, cell traps and microchips for the miniaturisation of biological research) and new tools for the high-throughput study of peptides and proteins. Mass spectrometry is the tool of choice for proteomics and peptidomics alike. “In close collaboration with industry we have demonstrated that improved mass spectrometry techniques can be used as scanning tools with a resolution as small as 30 µm. The technique is able to visualize the peptides or protein fragments directly on a biological surface, such as a tissue section or cell layer. In the coming years, we’d like to realize even better resolutions. The study of microorganisms on a subcellular scale is still several years away but an important and challenging technological goal to aim for!” ‘Innovative Peptide Biology’ In the past five years ABT has established a unique new research profile, fusing analytical biochemistry, microbiology, zoology and engineering expertise. Peptides are studied as part of a living system, not simply as isolated molecules. “You might call it innovative peptide biology,” explains Verhaert. “In this field there are plenty exciting fundamental challenges. Our results might even have a medical and pharmaceutical use.”