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.

NMR (Nuclear Magnetic Resonance) has emerged as an essential tool to determine the tridimensional structure of 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.

Manager : Carine van Heijenoort

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, …)

  • NMR Service

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.

Key Words

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

Since 2012, Nadine Assrir is a scientist in Eric Guittet’s team. She received a master of toxicology (Paris Descartes) and completed a PhD in biochemistry, molecular and cellular biology (Paris-Sud University) at the Institut Gustave Roussy. Her research projects focus on the relationship between structure and protein function including the impact of this relationship on the biological processes after post-translational modifications or molecular interactions. Currently, she is studying the impact of interactions of three proteins involved in cell proliferation, tumor reversion or cell motility, namely ErbB2, TCTP and iASPP. Her duties also include the co-management of the FRISBI platform (production of labelled proteins in eukaryotic cells). Nadine Assrir is also in charge of lessons in biochemistry, since many years, in the Bachelor and Master programs of the Versailles–St Quentin University.

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 ».

Jean-François Gallard is an NMR engineer.

François Giraud is an NMR engineer.

Carine van Heijenoort is a CNRS senior scientist. After studies in chemistry, she received her Ph.D. in 1994 in the group of Eric Guittet at the ICSN, with work on the characterization of internal flexibility of proteins by NMR. In 1999-2000, she went to Utrecht University as an invited scientist in the group of Rob Kaptein and Rolf Boelens where she explored her dutch roots and protein-protein interactions. Her research interests are focused on the characterization of multiple states of proteins and their link to function, with a particular interest on intrinsically disordered proteins and their interactions. She is currently coordinator of the department of Analytical and Structural Biology and Chemistry of ICSN. Outside the lab, Carine has three wonderful daughters, she actively practices horse riding, is fond of dogs, cats, music, reading and discussions with friends.

Eric Jacquet is CNRS research associate.

Ewen Lescop is a CNRS associate 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.

Annie Moretto est technicienne au CNRS.

Naïma Nhiri est ingénieure de recherche au CNRS.

Christina Sizun completed a PhD in Chemical Physics in 2000 at the Louis Pasteur University in Strasbourg, where she was trained in NMR spectroscopy of catalytic systems. She then joined the group of Burkhard Bechinger at the Max Planck Institute for Biochemistry in Martinsried as a post-doc to work on solid state-state NMR of membrane peptides. After a second post-doc in the team of Erick Dufourc at the Institut Européen de Chimie et Biologie in Bordeaux, she was recruited as a researcher in 2003 at the ICSN, where she developed her interest for structural biology by NMR. Her main focus is on the structure-function relationship of viral proteins (respiratory syncytial virus) as a member of a collaborative network including INRA and Institut Pasteur. She also participates to one of the projects dedicated to therapeutic targets in the frame of the LERMIT LabEx (modulators of the CXCL12/CXCR4 signaling axis). She is involved in teaching of biological NMR and biophysics in several university programs.

Membres non-permanents

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.

Florian Malard is a first year phD student at the Institut de Chimie des Substances Naturelles (ICSN) under the supervision of Ewen Lescop and Nadine Assrir. He is former student of the Paul Sabatier University (Toulouse III) and of the Ecole Normale Supérieure de Cachan. He also joined the Swiss Federal Institute of Technology Zurich for a one year internship before his phD. In the lab he aims to characterize the molecular basis of the interactions involving the TCTP protein and its partners using NMR. This is particularly relevant in the understanding of a biological process of interest: the tumoural reversion.

Louise Pinet is a PhD student at the Université Paris Saclay. Before, she attended the predoctoral program of chemistry at the Ecole normale supérieure of Paris, completed with a Master’s degree in Biophysics at the Université Pierre et Marie Curie. Her initial interest in physics and chemistry and the growing one in studying biological objects led her to protein NMR. Her PhD at the ICSN is about the structural and functional study of the intrinsically disordered C-terminal end of the protein ErbB2, supervised by Carine van Heijenoort and co-managed by Nadine Assrir. This PhD extends the Master’s internship she did in the NMR team on that same subject.

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.

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.

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.

Former members (since 2014)

  • Maria Grazia Concilio (Postdoc 2017-2018).
  • Corentin Jacquemoz (thèse 2017-): he continues his PhD thesis at CEISAM in Nantes.
  • Ludmilla Guduff (thèse 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 (Ph.D. 2011-2015) : Sanofi (France).
  • Safa Lassoued (Ph.D. 2012-2015)
  • Adrien Le Guennec (Ph.D. 2012-2015): Post-doc at University of Georgia (U.S.A.).
  • Marion André (Ph.D. 2012-2015): Cortecnet (France).
  • Sefano Caldarelli (Professor 2012-2015): Professor at Aix-Marseille Université (France).
  • Célia Deville (Ph.D. 2012-2015): Post-doc at Birkbeck University (U.K.).
  • Séverine Moriau (Ph.D. 2013-2016)
  • Nelson Pereira (Ph.D. 2013-2016)
  • Fataneh Fatemi (Ph.D. 2010-2013) : Beheshti Université of Tehran (Iran)