Frank Gabel

Short Biography

Frank Gabel works in the Biology, Deuteration, Chemistry and Soft Matter (BDCS) group at the Institut Laue-Langevin (ILL).

AMBER postdoctoral fellowship subject (Third call)

Developing new tools for structural biology of biomacromolecular complexes in solution: a joint SAXS/SANS contrast variation study of the membrane protein FhuA

Small angle X-ray (SAXS) and neutron (SANS) scattering are powerful techniques to probe the conformation and structure of bio-macromolecules, 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. While SAXS (especially when used at synchrotrons) allows a higher throughput and shorter exposure times, SANS has a particular strength of contrast-variation experiments and deuterium-labelling of sub-parts of bio-macromolecular complexes and thus allows to mask or highlight specific molecules in complex systems in an efficient way. While both techniques are complementary in the sense that they “see” different molecules (proteins, RNA/DNA, lipids…) differently, there are unfortunately few studies up 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/SANS 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 with SANS solvent contrast variation and specific deuteration of protein and lipid/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) protein, 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 and biomedically relevant biomacromolecular complexes in solution by a broad structural biology community.

Location: Grenoble, France

Organisation: Institut Laue-Langevin (ILL)

Links

AMBER call in EURAXESS main call (starting point for application)

Guide for applicants