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Institut de Biologie StructuraleGrenoble / France

Highlights

A new technique combining single molecule FRET, NMR and SAXS to describe intrinsically disordered proteins

Intrinsically disordered proteins (IDPs), i.e. proteins without stable three-dimensional structure, are extremely dynamic and it is precisely this dynamics that allows them to function and bind to different interaction partners very easily and efficiently. Rather than describing IDPs with a single structure, ensembles of many conformers have to be calculated to adequately represent their conformational landscape. In the past, nuclear magnetic resonance (NMR) spectroscopy and small angle X-ray scattering (SAXS) have been used to provide experimental input for the calculation of such ensembles. A precise description of specific long-range distances has, however, so-far been missing.
IBS/FDP researchers (Naudi-Fabra et al.) have now combined single molecule fluorescence spectroscopy, Förster resonance energy transfer (FRET) in particular, providing precise distances up to 10 nanometers, with NMR spectroscopy and SAXS in order to determine conformational ensembles in agreement with all those experimental data. The authors could show that their calculated ensembles were of predictive nature and reproduced independent data that were not included in the calculation of the model. This multidisciplinary approach thus opens up new possibilities for the quantitative description of intrinsically disordered proteins.

Quantitative description of Intrinsically Disordered Proteins using single molecule FRET, NMR and SAXS. Naudi-Fabra S, Tengo M, Jensen MR, Blackledge M, Milles S. J Am Chem Soc In Press (2021) https://doi.org/10.1021/jacs.1c06264

Contact : Sigrid Milles (Protein Dynamics and Flexibility by NMR Group)

An exclusive licence on a patented vaccine technology developed at IBS

The ’Adenovirus’ team led by Pascal Fender in the Methods & Electron Microscopy group at IBS is working on the adenovirus proteins involved in the entry of this virus, which infects many animal species and humans. This team discovered a non-infectious virus-like protein particle mimicking this virus : ADDomerTM. In 2016, in collaboration with the EMBL in Grenoble, the researchers modified this particle to expose epitopes of emerging viruses, leading to the creation of a new vaccine platform. After filing a CNRS/EMBL patent in 2017, the results were published in Science Advances in 2019 (Vragniau et al., 2019). In 2021, the British company Imophoron has just bought a licence for this patent and completed a 4.7M€ fundraising to perform preclinical studies and to test vaccines against three viruses : respiratory syncytial virus, chikungunya, and SARS-Cov2. It will validate the ADDomer as a platform for future vaccines development.

Contact : Pascal Fender (IBS/Methods & Electron Microscopy group)

Andrea Dessen recipient of the CNRS silver medal

Andrea Dessen, team leader of the Bacterial Pathogenesis group, has been awarded the 2021 Silver Medal of the CNRS. This medal is presented to a researcher for the originality, quality, and importance of their work, which is recognized at national and international levels.

Andrea Dessen is graduated with a degree in Chemical Engineering from the University of Rio de Janeiro. She did her PhD work at New York University and her postdoctoral training both at the Albert Einstein College of Medicine (New York) and at Harvard Medical School (Boston), the latter with Pr. Don C. Wiley. She then worked as a staff crystallographer at Genetics Institute/Pfizer in Cambridge, MA, in the Small Molecule Drug Development Dept. Upon moving to France, she was hired by the CNRS in 2000 in Dr. Otto Dideberg’s laboratory at the IBS. As a CNRS Research Director she has been the head of the Bacterial Pathogenesis group at the IBS since 2012. In addition, she also directs a 2nd group at the Brazilian Biosciences National Laboratory (LNBio/CNPEM) in Campinas, São Paulo, thanks to a Laboratoire International Associé (LIA) partnership between the CNRS and the CNPEM in Brazil.

The main interest of both groups involves the structural and functional characterization of bacterial virulence factors and cell wall biosynthesis machineries, as well as the identification of novel antibacterial compounds in natural product libraries. The main techniques employed by the teams include X-ray crystallography, electron microscopy, high throughput screening and natural product characterization, as well as biochemical, biophysical and microbiological approaches.