Structural Biology and Chemistry

The organization of the cell involves a very number of molecules (proteins, nucleic acids, small molecules). They represent a network of interactions that controls the development and the regulation of many biological processes. It is then of high interest to understand how these molecular components work independently and in presence of their natural partners. Il est donc particulièrement important de comprendre comment ces composants moléculaires fonctionnent de façon isolée et au contact de leurs partenaires naturels.

NMR (Nuclear Magnetic Resonance) has emerged as an essential tool to determine the tridimensional structure these macromolecules at high resolution, together as X-Ray cristallography. In addition, NMR provides a wealth of information about the internal motions in terms of time scales, amplitudes and spatial localization. Furthermore, this technique is able to provide the structural characterization of intermolecular interactions between molecules from different families.

More generally, understanding the properties of molecular complexes of high and weak affinities opens the route to the development of biologically active molecules.

NMR has already proven to be highly efficient in this field. However, the development of new NMR methods can still extend the range of applications of NMR in biology.

NMR is also an essential tool in analytical chemistry, particularly for the analysis of complex mixtures, with applications in metabolomics, natural product research or reaction monitoring. Methodological developments, especially for multidimensional techniques, extend the scope and potential of NMR spectroscopy.

Organisation

The NMR team is divided in three different axis:

  • Research in Structural Biology and Development of new NMR Methods

The research is mainly centered on the analysis of structure, interactions and dynamics of biological macromolecules in solution by NMR. Most of our projects are selected for their biological relevance and their potential applications. Depending on the projects, we also use different methods such as X-Ray crystallography, ITC, … A number of our projects are at the edge of NMR possibilities (size of the systems, solubility, high flexibility, and require the use of state of the art NMR techniques. We are thus also highly interested in methodological developments for structural biology but also for fast multidimensional NMR and on varions forms of hyperpolarisation. A number of projects are developped in collaboration with groups of biologists or chemists at the national level (CEA, INSERM, INRA, Pasteur Institute, universities of PARIS XI, Nantes, Marseille, …) and international level (Southampton University, EPFL Lausanne, …)
When necessary, we also use the best adapted technique, which leads to the use of X-ray crystallography, microcalorimetry, biological tests, cell biology, etc.

  • NMR Service

We continue our long tradition of applying NMR to chemistry. The chemists of ICSN have access to several NMR spectrometers (a two 300MHz, two 500MHz and a 600MHz) on a self-service basis for simple experiments. A computarized reservation system allows the users to book their time via the network and to check at any time for an available measurement time.
For difficult cases, they benefit from the assistance of the engineers of the team who realize the needed experiments, possibly at higher fields. These engineers also realize a number of more demanding NMR studies in the fields of chemical synthesis or natural products structure determination for chemists either from the institute or from external laboratories.

  • 950 MHz national facility

Installed in december 2008, the 950 MHz spectrometer operates as a national facility. For more information, visit the facility webpage.

Keywords

NMR, Proteins, Nucleic Acids, Structure, Dynamics, Interactions

Skills

Molecular Biology, Protein production and purification, Isotope labelling of protein, Small molecule and protein NMR, XRay cristallography, SAXS, Molecular modelling, Structure determination, Enzymology, Molecular interactions

Equipment

For Structural Biology:

  • 5 NMR Spectrometers: 2 * 600 liquid with cryoprobe, 700 solid/liquid, 800 MHz liquid with cryoprobe, 950 MHz liquid with cryoprobe, samplejet, high pressure NMR, cluster 8×32 PCUs, microcalorimetry, and equipment for molecular biology, purification, cellular biology.

For Structure Determination (chemistry):

  • two 300 MHz, two 500 MHz, and one 600 MHz

Senior staff

François Bontems is a CNRS senior scientist (DR2). After his PhD on the structural organization of scorpion toxins in the Centre d’étude nucléaire de Saclay, he joined the NMR team led by Jean-Yves Lallemand at the Ecole polytechnique. He mainly worked on a system coupling RNA translation and inactivation during E. coli infection by the T4 phage (« S1-RegB » system). Then, he integrated the NMR group at ICSN and currently shares his time between this team and the Structural virology unit at Pasteur Institut. His present interests mainly concern the structural properties of the E and NS1 proteins of flaviviruses (yellow fever, dengue and Zika), which are the main targets of the immune system after an infection. In this aim, he developed and implemented at ICSN some tools allowing the labeling with stable isotopes of these proteins that can not be produced in E. coli and are generally expressed in insect or mammalian cells. In addition, he also organises colloquia devoted to science and society relationships and is responsible of a Pasteur course on the same topic. He is also member of the steering committee in charge of a Livre Blanc « society, higher education and research ».

Claire de March is a CNRS Assistant professor (CRCN). She trained in flavor science and industry at the ISIPCA in Versailles and had an industry experience as a sensory analyst in the Bel group. She received her Ph.D. at Université Nice Côte d’Azur in 2015 where she investigated the molecular mechanisms involved in odorant receptor recognition of odorant molecules. From 2016 to 2022, she joined the Hiroaki Matsunami lab at Duke University (NC, USA) to continue studying how odorant receptors are used to trigger an odor percept but on the bench side. Since 2022, she joined ICSN as a CNRs assistant professor. She uses the synergy of in silico and in vitro approaches to establish the link between the chemical structure of an odorant molecule, the biological processes involved, and the sensation it causes. She is particularly interested in role of evolutionarily conserved amino acid patterns in odorant receptors and how that defines their identity and structure within the GPCR family. Outside of the lab, she practices many types of crafts and Thai boxing and enjoys relaxing time with her friends and family.

Jean-François Gallard is an NMR engineer.

Diego Gauto had received his M.Sc. in chemistry (2009) and Ph.D. in computational biology (2013) from the school of sciences at Buenos Aires University, Argentina. Immediately after his PhD, he took a postdoctoral position in solution NMR at the Institute of Molecular and Cell Biology of Rosario (IBR), Argentina and then move to France to start a postdoctoral positions at IBS (Institut de Biologie Structurale) with Dr. Paul Schanda to study protein structure and protein dynamic by solid state NMR and developing methods for structural elucidation combining NMR and CryoEM. Then, he continues his postdoctoral training with Drs. Sabine Hediger and Gaël De Paëpe at CEA, Grenoble in order to perform NMR under cryogenic temperatures and DNP conditions. From 2020 to nowadays, he is a CNRS research assistant scientist at the Institut de Chimie des Substances Naturelles (ICSN), Gif-sur-Yvette where he is interesting in understand the structural basis of protein cages and their application in the chemistry and health.

Eric Jacquet is CNRS research associate.

Ewen Lescop is a CNRS senior scientist. He received his Ph.D. at the ICSN in the group of Eric Guittet, with a work on a honeybee odorant-binding protein. He then performed postdoctoral research at Beijing University (2004-2006, C. Jin, China) and the Institute of Structural Biology (2006-2007, B. Brutscher). In 2007 he returned to the ICSN to develop NMR methods for proteins and study a variety of biological systems with structural-biology approaches. Outside the lab, Ewen is a keen and active player of traditional folk music, especially breton music, and he always likes a good meal and a drink.

Nelly Morellet is a research engineer (CNRS-IR1). She obtained her Ph.D. with Jean-Claude Beloeil in 1989 at the ICSN. From 1990 to 2010 she studied several viral proteins by NMR (VIH-1, SIV, Birnavirus, Rotavirus…) in the group of B.P Roques then D.Scherman at the School of Pharmaceutical and Biological Sciences in Paris. In 2010, she joined the BCS group at the ICSN. She is involved in several projects: antibiotic resistance (NDM-1 protein), transposases and domesticated transposases (PiggyBac and PiggyMac proteins), and Buruli ulcer (N-Wasp protein).

Annie Moretto is a CNRS technician.

Naïma Nhiri is CNRS research engineer.

Non-permanent members

Christophe Cardone is a PhD student supervised by Christina Sizun. He works on the structural characterization of complexes between respiratory syncytial virus proteins and cellular proteins as antiviral targets. Previously, he completed a Bachelor’s degree in Biochemistry and Molecular Biology at Paul Sabatier University (Toulouse III) and a Master’s Degree in Engineering and Chemistry of Biomolecules at Paris Saclay University. During his university course, he did an internship in theoretical chemistry at the Laboratory of Physics and Chemistry of Nano-Objects and at the Institute of Pharmacology and Structural Biology of Toulouse on the screening of ligand on a therapeutic target of cancer.

Claire-Marie Caseau is a PhD student at Paris Saclay University under the supervision of Christina Sizun. Her thesis focuses on the structural characterization of Respiratory Syncytial Virus’ interferon antagonists. Previously, she completed a Bachelors of Science in Biology/Biochemistry at Haverford College (PA, USA) as well as a Masters of Chemistry at Paris Descartes University (in partnership with Paris Saclay University), during which she spent six months at the University of Groningen in the Netherlands.

Camille Doyen is a PhD student at the Institut de Chimie des Substances Naturelles (ICSN) under the supervision of Ewen Lescop and Christina Sizun, in collaboration with Sanofi. Graduated from the chemistry school of Strasbourg (ECPM), she had the opportunity to gain first experiences in the R&D laboratory of Pfizer in England, then by an internship at the institut des sciences analytiques (ISA) of Lyon under the supervision of Torsten Herman. Her PhD project deals with the study of peptide-liposome system to optimize peptides and liposomes structures, encapsulation efficiency and kinetics of release.

Ghanem Hamdoun is a postdoctoral fellow under the direction of Dr. Jean Nicolas Dumez. He is working on the development of ultrafast 2D NMR methods based on diffusion and dipole–dipole cross correlations, in order to exploit them to analyse gold catalytic reactions. He received his Ph.D. in 2014 (Rouen University-COBRA Laboratory) in the group of Hassan Oulyadi. His research projects focus on the development and application of new NMR methods for structural characterization of organolithium complex at low temperature. He continued this work during a first post-doctoral internship and was particularly interested in the implementation of ultrafast 2D NMR methods for the aggregation and solvation study of organolithium complexes.

Former members (since 2014)

  • Maria Grazia Concilio (Postdoc 2017-2018).
  • Corentin Jacquemoz (PhD thesis 2017-): he continues his PhD thesis at CEISAM in Nantes.
  • Ludmilla Guduff (PhD thesis 2015-2018)
  • Jean-Nicolas Dumez CNRS Research Associate (CRCN) at ICSN (2014-2018). Jean-Nicolas moved to CEISAM, Nantes in 2018.
  • Arthur Besle (CDD IT)
  • Hans Lafaille (CDD IT)
  • Prishila Ponien (CDD IT)
  • Oriane Frances (PhD thesis 2011-2015) : Sanofi (France).
  • Safa Lassoued (PhD thesis 2012-2015)
  • Adrien Le Guennec (PhD thesis 2012-2015): Post-doc at University of Georgia (U.S.A.).
  • Marion André (PhD thesis 2012-2015) : Cortecnet (France).
  • Sefano Caldarelli (Professor 2012-2015): Professor at Aix-Marseille Université (France).
  • Fataneh Fatemi (PhD thesis 2010-2013): Beheshti University of Tehran (Iran)
  • Séverine Moriau (PhD thesis 2013-2016)
  • Nelson Pereira (PhD thesis 2013-2016)
  • Célia Deville (PhD thesis 2012-2015): Post-doc at Birkbeck University (U.K.).