Optimisation of crystal growth using a microfluidic technology-based crystallization bench

Applications are invited for an Early Stage Researcher (ESR)/PhD studentship position funded by The Marie Skłodowska-Curie Actions (MSCA) Innovative Training Networks (ITN) programme “Rationalising Membrane Protein Crystallisation” (RAMP) and based in the Synchrotron Group at the Institut de Biologie Structurale (IBS), France. The Institut de Biologie Structurale (IBS) is a research center for integrated structural biology funded by the CEA, the CNRS and the Université Grenoble Alpes (UGA).

Over the last 20 years a combination of experimental and computational work has greatly advanced the understanding of the nucleation and growth of crystals in many systems, from ice to globular proteins. In contrast membrane protein crystallisation has remained mainly empirical. Here we aim to apply predictive models and microfluidic techniques to membrane protein crystallisation as a means of tailoring crystal sizes and morphologies for different downstream structure determination approaches. This PhD project is one of 12 in the RAMP training network. Other PhD students in the RAMP network will develop advanced methods for crystallisation and modelling of the membrane protein crystallisation process and apply it for the structure determination of important membrane proteins.

This project focuses on the specific challenges of membrane protein crystallisation where precise control of the crystal size and morphology is essential. This includes neutron crystallography requiring large crystals, with volumes of > 0.01 mm3 and serial femtosecond crystallography requiring uniform populations of small microcrystals of 1-20 μm.

The objective of this PhD project is to further develop and adapt our current flow-cell dialysis bench (Junius et al., 2016, J. Applied Cryst., 49, 806-813) to the crystallization of membrane proteins for both neutron and time-resolved X-ray crystallography. The technological goal of the PhD student will be to re-design the temperature-controlled fluidic device to successfully integrate in situ UV spectroscopy. An important part of the work will be devoted to exploring phase behavior in lipid-based multicomponent systems and using statistical modeling to rationally improve the final stages of crystallization of membrane proteins. The project will involve secondments to other network partners with specialised membrane protein crystallisation and computational/theoretical modelling expertise such as University of Leeds, University of Aarhus, University of Surrey and University of Maynooth, and co-supervision of NatX-ray.

This project will involve crystallisation and X-ray and Neutron diffraction analysis of crystals of model membrane proteins, as well as instrumentation, automation and methodological development in protein crystallography, with support from the existing expertise in the group. Crystals will be studied at national and international synchrotrons, neutron sources and free electron lasers.

We are looking for an enthusiastic academically qualified (bio)physicist, physico-chemist or engineer with a strong interest in structural biology and multi-disciplinary problems. Experience in macromolecular crystallization and or crystallography is an advantage. Given the scope of the project and the need for a close collaboration with other Consortium members as well as with the industrial/external partners, excellent communication skills and the ability to work as part of a team are prerequisites.

Candidates must comply with EU and Université Grenoble Alpes eligibility criteria. Due to the EU rules to promote mobility, you are not eligible for a position in a country where you have lived (worked, studied) for more than 12 months in the last 3 years. So for this position you are eligible, unless you have studied or worked in Denmark for more than 12 of the last 36 months. For applicants finishing or who have just finished their degree, this typically means that you can be graduating from any university except a Danish university.

Further details on this project are available from Dr. Monika Spano ([Email Address Removed]). Please see the RAMP website (www.ramp.itn.eu) for more information on the network, and http://opticrys.neowordpress.fr/ for more information on Dr Monika Spano’s research. Further details about the Université Grenoble Alpes, the Institut de Biologie Structurale and the Synchrotron Group are available at http://www.univ-grenoble-alpes.fr/en/, http://www.ibs.fr/spip.php?lang=en, http://www.ibs.fr/research/research-groups/synchrotron-group/.

Details on how to apply are available on the RAMP website, www.ramp.itn.eu.