Supramolecular and Biological Chemistry
- 2005- Assistant professor and Queen’s National Scholar, Queen’s University (Kingston, Canada)
- 2004-2005: Maître de conférence associé, Collège de France (Paris/Strasbourg, France)
- 2002-2004 : Lavoisier post-doctoral fellow with Prof. Jacqueline K. Barton, Caltech (California, United States of America): “Bifunctional Metallo-intercalators for Anti-cancer Applications”
- 1998-2002: PhD fellow with Prof. Jean-Marie Lehn, Université Louis Pasteur (Strasbourg, France): “Molecular Self-organization and Switching”
- 1994-1998: Élève normalienne, ENSLyon (Lyon, France) : “Synthesis of Europium Complexes based on a Cyclotriveratrylene Scaffold; Application to Photo-and Electroluminescence”
- 1996 : Research assistant with Prof. Christopher A. Hunter, University of Sheffield (Sheffield, United Kingdom): “Synthesis of a Self-Assembling System Based on Porphyrin Units, a Synthetic Model for Vernier Length Generation”
- 1995: Research assistant with Dr. Jean-Claude Marchon, Commissariat à l’énergie atomique (Grenoble, France) : “Synthesis of a porphyrin bearing bulky chiral meso-substituents and its metallic complexes; application to chiral recognition and asymmetric catalysis”
- 1991-1994 : Classes préparatoires, lycée Hoche (Versailles, France)
- 2005 : Queen’s National Scholar award, Queen’s University (Canada)
- 2003 : Lavoisier Post-doctoral Fellowship, Ministère des Affaires Étrangères (France)
- 1998 : PhD fellowship, Ministère de l’Éducation Nationale, de la Recherche et de la Technologie (France)
- 1994 : Admission to the ENSLyon
Bio-organic and bio-inorganic projects: Targeting DNA
The genetic information contained in our DNA defines what we look like and how our body functions. It resides in several features:
(i) the atomic information : expressed through the hydrogen bonding pattern on each nucleic base; this is included in the primary structure,
(ii) the local information : expressed in the conformation adopted by a fragment of DNA; this defines secondary structures such as the A, B and Z duplexes, quadruplexes, four-way junctions…
(iii) the deviations from ideal secondary structures, which may include stacked non-base-paired nucleic bases in a duplex, flipped-out bases, bending and untwisting.
(iv) the overall packaging (e.g. chromosome compaction).
All these features are a source of information for the recognition of DNA.
1) In the lab we design, synthesize and study organic and inorganic DNA targeting sensors based on each of the first three features. These indeed mark important sites of either “healthy DNA” that we want to target (e.g., telomeres) or damaged DNA. In particular we are interested in detecting molecular and supramolecular alterations related to cancers (e.g. skin, lung and liver cancers). In the latter case, the goal is to use our targeting agents to yield a signal that may be (i) detected with a physical response (e.g. luminescence for diagnostics), (ii) detected by proteins and enzymes for in situ biological responses (e.g. after cleavage or distortion). Sensors based on the same design may also be used to monitor the presence of carcinogens in our environment (water, air) before they reach our body.
2) In addition to designing binders, we are also interested in letting the target DNA select its own preferred substrate from a library of dynamically exchanging potential binders (why should we do all the work ?!).
Dynamic chemistry: molecular and supramolecular projects:
1) Self-assembled responsive artificial ion channels: self-assembly is a process that lets a molecule assemble according to the electronic information within its structure, as is typically illustrated by DNA A, B and Z duplexes. As the interactions are dependent on the environment (solvent, salt concentration…), so is the outcome of the assembly. We are using this stimuli dependent organization of matter to assemble artificial ion channels whose structure should depend on voltage, light, solvent, or salt concentration. The design of our molecular building blocks also allows fixing the assembly into easily characterizable covalent architectures.
2) As is illustrated by DNA self-assembly, the hierarchy of information involved in the formation of complex architectures is of interest (hydrogen bonding, then pi-stacking and salt effect…). Hence, small projects in the lab focus on defining pathways for a cascade of interactions to take place and yield highly complex architectures from very simple tectons.
Collaborations: In addition to in-house preliminary characterizations, active collaborations are essential to our activities. The characterizations of potential artificial ion channels are conducted in collaboration with Dr. Louis Cuccia (Concordia University, Montreal). Potential anti-cancer agents are being studied at the Museum d’Histoire Naturelle (Paris, France) by Dr. Jean-Louis Mergny and at the Centre de Lutte contre le Cancer d’Auvergne (Clermont Ferrand, France) by Prof. Pierre Verrelle and Dr. Andrei Tchirkov. The studies of DNA binders are also complemented at the Centre de Biophysique Moléculaire (Orléans, France) by the team of Dr. Jean-Marc Malinge. Dr. Marc Schmutz and Dominique Sarazin (Institut Charles Sadron, Strasbourg, France) are also key collaborators in the structural characterizations of dynamic systems.
Useful links and fun chemistry pictures:
Chemistry at Queen’s University:
Chemistry worldwide: http://www.liv.ac.uk/Chemistry/Links/international.html
Supramolecular Chemistry in Europe: http://www-isis.u-strasbg.fr/
Education: Periodic table: http://www.chemicool.com/
Patiently assembled…! Quickly swallowed
Sometimes it breaks nicely