About the Project
Applications are invited for an Early Stage Researcher (ESR)/PhD studentship positions 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.
Our research focuses on moving away from conventional miniaturisation of the crystallisation experiment via smaller drops, and to focus on miniaturising a crystallisation device that allows precise control of the experiment, unlike vapour diffusion. We have already produced a device that allows batch temperature controlled crystallisation suitable for growth of large crystals for neutron diffraction experiments (Budayova-Spano et al., 2007 Acta Crystallogr. D, 63(3), 339-347). The aim of this project is the precise and reversible control of crystallisation via dialysis and temperature, but at the nano scale. We have already developed a crystallisation bench that provides temperature and dialysis control and uses just 15 μl (Junius et al., 2016, J. Applied Cryst., 49, 806-813); the technological goal of this PhD project is to pursue miniaturisation of this technology into microfluidic chips using only 200 nL protein sample but also allows real-time monitoring of crystal growth.. The major challenge is the integration of fluid handling capabilities enabling rapid mixing for reaction initiation. The chip should of course be X-ray compatible, allowing in situ X-ray diffraction. Finally, this microfludidic pipeline will be applied to the growth of biologically and medically relevant membrane protein crystals for serial X-ray crystallography and time-resolved crystallography.
The project will involve secondments to other network partners with specialised membrane protein crystallisation, microfluidic and crystallography expertise such as Trinity College Dublin, University of Aarhus, AstraZeneca, CNRS Bordeaux and the Hamburg Centre for Ultrafast Imgaging, and cosupervision of Molecular Dimensions Ltd.
This project will involve crystallisation and in situ X-ray diffraction analysis of crystals of model as well as difficult membrane protein targets, as well as instrumentation, automation and methodological development in microfluidics and 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 France 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 French 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 at the RAMP website, www.ramp.itn.eu.
Funding Notes
The PhD students (Early Stage Researchers (ESR)s in EU jargon) will be paid a salary in line with the, generous, MSCA requirements, for 36 months. The exact salaries will be confirmed later, but MSCA salaries are significantly above, for example, the standard UK PhD stipend of £15,000 (€17,000) per year.
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