Research fellowship - AMBER cofund project

Institut Laue-Langevin (ILL)

Okänd ort

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This research fellow position is part of the EU cofund research project AMBER, Advanced Multiscale Biological imaging using European Research infrastructures, which aims to address scientific and sectoral gaps in biological imaging ranging from molecular, through cellular, to tissue, organ and organism levels of organisation, and is coordinated by the LINXS Institute of advanced Neutron and X-ray Science.
AMBER is funded by the EU Marie Sklodowska-Curie (MSCA) COFUND scheme.
Around 10 postdocs/research fellows will be recruited in the third call 2024/2025, with each fellowship lasting 36 months.
More information about all of the announced post-doctoral/research fellow positions within the AMBER co-fund project: https://www.euraxess.se/jobs/289120

Your work may include clinical and biomedical projects. It may also include technique development work aimed at combining imaging techniques and data analysis to provide a more integrated picture of life processes in the context of health and disease. As a research fellow at the AMBER programme, you will acquire unprecedented medical, biological, and methodological capabilities, with a profound potential impact for Europe's next generation of research and researchers. When you have completed the AMBER programme, you will be extraordinarily well equipped to further your career in academia, at infrastructures, in the health and MedTech sectors, and beyond.

Context
This 3-year research fellowship is part of the EU Marie Sklodowska-Curie (MSCA) COFUND research project AMBER, Advanced Multiscale Biological imaging using European Research infrastructures. This project will address scientific and sectoral gaps in biological imaging ranging from molecular, through cellular, tissue, organ and organism levels of organisation, and is coordinated by the LINXS Institute of advanced Neutron and X-ray Science.

AMBER has six core partners: Lund University/MAX IV, Sweden, the European Spallation Source (ESS), Sweden, the European Molecular Biology Laboratory (EMBL), the Institut Laue-Langevin (ILL), France, the International Institute of Molecular Mechanisms and Machines (IMOL), Poland, and the Leicester Institute of Structural and Chemical Biology, United Kingdom. For more information about AMBER, visit: https://www.ambercofund.eu

Description of the ILL's Project
Small-angle X-ray (SAXS) and neutron (SANS) scattering are powerful techniques to probe the conformation and structure of biomacromolecules, as well as their interactions in solution on a nanometer scale. Both techniques are complementary: X-rays being sensitive to the electron densities, and neutrons being sensitive to neutron scattering length densities of the solubilized molecules and the surrounding solvent [Mahieu & Gabel, Acta Cryst. D 2018]. While SAXS (especially when used at synchrotrons) allows a higher throughput and shorter exposure times, SANS has a particular strength for contrast-variation experiments and deuterium-labelling of sub-parts of biomacromolecular complexes and thus allows to mask or highlight specific molecules in complex systems in an efficient way [Härtlein et al. Meth. Enzymol. 2016]. While both techniques are complementary in the sense that they "see" different molecules (proteins, RNA/DNA, lipids.) differently, there are few studies to date using SAXS and SANS jointly and in a systematic way in order to analyse the internal structure of important and complex biological assemblies (e.g. protein-RNA/DNA complexes or solubilized membrane proteins).

In the present AMBER postdoc project, we propose to advance the state-of-the-art of combined SANS/SAXS analysis of biomacromolecular complexes in solution by a joint and extensive SANS and SAXS contrast-variation study of a solubilized membrane protein complex. We will combine a recently developed approach of solvent-contrast variation SAXS [Gabel et al. IUCrJ 2019; Gabel et al. Acta Cryst. D 2022] with SANS solvent-contrast variation and specific deuteration of proteins and lipids/nanodiscs of a solubilized FhuA membrane protein model system. This novel combination is expected to provide unprecedented insight into structural details of the complex in solution, due to the unusually broad range of complementary contrast conditions of (hydrogenated or deuterated) proteins, lipids and nanodiscs with respect to X-rays and neutrons in different solvent conditions (H2O/D2O in the case of SANS, and electron-rich contrast agents in the case of SAXS). Once validated for our
membrane protein model system, we expect this novel approach to be applicable to a multitude of structural studies of important
biomacromolecular complexes in solution.

Principal investigator
Frank Gabel is the head of the "Biology, Deuteration, Chemistry and Soft Matter" (BDCS) group at the Institut Laue-Langevin,
Grenoble. His personal research activity focuses on integrated structural biology approaches, in particular using small-angle
neutron (SANS) and X-ray (SAXS) scattering to study challenging biomacromolecular complexes of biological and biomedical
importance in solution.

Minimum requirements
- PhD in physics or structural biology/chemistry, with excellent knowledge of biochemistry and molecular biology, including
experience in protein expression, purification and characterization by biophysical techniques (e.g. SEC-MALLS)
- Experience in small-angle neutron and X-ray scattering (data collection, data reduction and analysis) would be desirable
- Applicants need to have a maximum 8 years after a doctoral degree (PhD), as required by the Commission, in accordance
with the Horizon-Europe MSCA COFUND project Grant Agreement.
- At least one original publication in a peer-reviewed journal.
- A complete application package submitted through the AMBER portal (including CV and detailed research plan).
- Strict compliance with the MSCA mobility rule that the researcher must not have resided or carried out his/her main activity
(work, studies, etc.) in the host organisation's country for more than twelve months in the three years immediately prior to
the call deadline.
- Applicants should be fluent in English, have good communication skills and should demonstrate their ability to develop and
conduct high-quality research, both in a team and independently.
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