Chaperones are central to protein folding, but their action at the ribosome remains poorly understood. The highly dynamic nature of polypeptide synthesis, folding, and chaperone binding presents an intriguing puzzle, which is difficult to resolve with existing methods. We address this question using a powerful combination of two new tools that span from single-molecule events to genome-wide patterns. Our lab has pioneered the use of optical tweezers to detect how chaperones mediate conformational changes in proteins (Science 2007, Nature 2013, Nature 2016). We now integrate this technique with single-molecule fluorescence, which allows us to monitor for the first time the dynamic interplay between chaperone binding and protein folding at ribosomes. This new approach provides unprecedented rich data on molecular events in real time, and provides the opportunity to develop new models and discover fundamental mechanisms. In collaboration with others, we combine this approach with ribosomal profiling data that reveals the genome-wide patterns of chaperones binding to the ribosome during translation. These techniques to study conformational changes within protein complexes will be relevant to a wide range of protein-protein interactions.
Our Biophysics research group focusses on three themes:
Folding pathways are traditionally studied for proteins in isolation, even though chaperones are critical to achieving native folds. Consequently, the mechanisms by which chaperones act remains poorly understood. We address this question with a single-molecule approach, using optical tweezers, protein constructs, and computer modelling (Science 2007).
The stochastic nature of gene expression is increasingly understood, but how it impacts growth and fitness remains unclear. We investigate this issue using genetic engineering, microfabricated flow-cells, single-cell time-lapse fluorescence microscopy (EMBO rep. 2009).
Evolutionary processes are typically studied in constant environments, and a descriptive manner. As a result, the evolutionary dynamics in variable environments has been barely addressed, even though this is considered central to the evolution of complex biological functions. Using synthetic biology and mathematical modelling, we aim to bring a more predictive approach to these fascinating issues (Nature 2007)
Past research topics include single-molecule studies on DNA packaging by bacterial viruses, and carbon nanotube-based electronics.
More biophysics on tansgroup website.
You will need to meet the requirements for an MSc-degree, to ensure eligibility for a Dutch PhD examination.