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Fascinated by the remarkable dynamics of protein function and cutting-edge biophysics technology? Owing to recent breakthroughs, it is just now becoming possible to follow the internal action of the most intricate biomolecules. Our group has pioneered the study of increasingly large chaperone-protein complexes at the level of individual molecules. Our excitement lies in seeing their dynamic behavior for the very first time, and to hence reveal how and why they perform their functions and enable the critical cellular processes that underpin life. Previously, we have shown how proteins can be clamped, confined, and processively pulled on by protein processing machines, in order to fold proteins and suppress protein aggregation and disease. Our focus now and the coming years is on ubiquitin-mediated protein processing machines and ribosomes – one of the most complex and crucial biomolecules in our cells.
In this project, you will will study a yet unknown mechanism, namely how proteins are assembled actively in a non-equilibrium manner. This assembly mode starkly contrasts with the current model that is based on random diffusion of protein subunits coming together to form a complex. Such active assembly powered by the translation of ribosomes was recently discovered by us, but the mechanism is unknown. By probing individual protein chains emerging from the ribosome and employing single-molecule fluorescence, you will have unprecedented insight into this phenomenon. The aim is to understand the general principles and how they help expand the range of proteins that cells can produce. Intrigued how this molecular mechanism could work? Check out our website or send us an Email.
You will drive the conceptual development of new experimental schemes, the use of cutting-edge single-molecule fluorescence and manipulation methods, the adaptation of existing biochemical protocols, the automated analysis of complex data, the formulation of new models, and the writing of scientific papers that explain your findings. We have a lively and close-knit research group of about 10 PhD students and postdocs, which work together in small teams on various projects in a highly supportive and social atmosphere that extends to the other research groups at the AMOLF institute, which is housed in a modern building in the east of Amsterdam.
What makes this project also special is that it is part of a larger collaboration with leading groups at Heidelberg University and the ETH in Zurich, which use novel sequencing and cryo-EM methods. By integrating these methods, we aim to push the limits of technical possibility, and to provide insights of unprecedented detail, spanning from the cellular to the atomic level, from in vivo to in vitro, from genome-wide patterns to molecular mechanisms, and from bacteria to human cells. This initiative is motivated by our recent discovery that multiple ribosomes cooperate to actively drive protein-complex formation, and the now urgent need to elucidate the underlying mechanisms and scope throughout the cell. As a member of this team, you will therefore also become intimately familiar with a wide range of methods which will be critical to advances in protein science in the coming decades.
We are looking for several outstanding experimental physicists or chemists with an interest in single-molecule techniques, programming skills to handle complex data, and who will thrive in a diverse and collaborative environment. Excellent verbal and written English skills are essential. You meet the requirements for an MSc-degree to ensure eligibility for a Dutch PhD examination.
Conditions 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, with a starting salary of gross € 2,590 per month and a range of employment benefits. 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 foreign PhD-student with housing and visa applications and compensates their transport costs and furnishing expenses.