PhD-student: Nano-mechanical dynamics of single protein-chaperone complexes, studied with optical tweezers and super-resolution fluorescence
Despite the profound importance of chaperones to all proteins, the principles of their action remain surprisingly mysterious. We know that polypeptide chains fold into complex structures, but how can another protein help to solve this puzzle? The structure and function of chaperones like Hsp70 and GroEL has been studied extensively, but traditional methods are not well suited to detect the crucial conformational changes of their client proteins. Recently it has become possible to do so. We have pioneered the use of optical tweezers for this purpose, and for instance applied it to the chaperones SecB, Trigger Factor, and Hsp70 (Science 2007, Nature 2013, Nature 2016). We are integrating single-molecule fluorescence visualization at super-resolution precision, and developed methods to probe single actively translating ribosomes and their associated chaperones. In this project, you will measure the conformational and compositional dynamics of key chaperone systems for the first time, and further extend the capabilities of single-molecule detection.
About the group
Our 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.
See also tansgroup.amolf.nl
We are looking for an outstanding experimental physicist or chemist with an interest in single-molecule biophysics, and a strong drive to excel in a ambitious international environment.
Terms of employment
The position is intended as full-time (40 hours / week, 12 months / year) appointment in the service of the Netherlands Foundation of Scientific Research Institutes (NWO-I) for the duration of four years. After successful completion of the PhD research a PhD degree will be granted at Delft University of Technology. Several courses are offered, specially developed for PhD-students. AMOLF assists any new PhD-student with housing and visa applications and compensates their transport costs and furnishing expenses.
Prof. dr. ir. Sander Tans
Group leader Biophysics
Phone: +31-(0)20-754 7100
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