Chemical Biology

Presentation of the department

The department of Chemical Biology is naturally positioned at the interface between synthetic Chemistry and Biology. The department’s staff combines expertise in highly complementary disciplines such as organic (glycochemistry, peptide chemistry, molecular probes) and inorganic synthesis (organometallic lanthanides or transition metals complexes), in cellulo or in vitro chemistry, biochemistry and molecular biology, enzymology. This diversity of talents is federated around a common interest for the investigation of biological events, the design and elaboration of new tools and strategies for their study, their understanding, and potentially their regulation. Chemistry is principally concentrated on the search for properties or function, although this is not exclusive of the development of new, original methods or synthetic strategies, and the search for reactivity. Biology is mainly focusing on redox signaling in mammalian cells with a strong interest in nitrogen monoxide (NO) and hydrogen peroxide, two chemical messengers capable of triggering biological response, and two of their target proteins, including Fe-S proteins. The biological targets are selected according to their academic and/or societal interest, and find applications in various domains such as microbiology, agronomy or human health. Research conducted in the department can also find inspiration in the observation of biological processes, to construct new molecular objects with an interest for health and sustainable development. The department of Chemical Biology is organized around two thematic groups, entitled « Probes and modulators for biological targets » and « Oxidative stress, Iron-Sulfur proteins ans cancer », and a screening platform named « CiBi – Cibles Biologiques », focusing on the biological evaluation of small molecules

Mots-clefs : Chemistry-Biology interface, probes, modulators, cancer, infection, molecular imaging, click-chemistry, organic and inorganic chemistry, glycochemistry, biological targets, cell labeling, enzymology, biochemistry, molecular biology, redox, oxydative stress, Fe-S proteins, iron homeostasis.

Permanent Researchers

Dr. Marie-Ange BADET-DENISOT graduated in biochemistry at P. & M. Curie University (Paris VI) and got her PhD in molecular and cellular pharmacology (1990, P. & M. Curie University) under the guidance of Bernard Badet. Following postdoctoral work with Professor H. Zalkin at Purdue University (USA), she was recruited as a CNRS research associate in 1992 and joined the Chemical Institute of Natural Products in Gif-sur-Yvette in the bioorganic group of Dr. B. Badet. She obtained her HDR in 1999 at P. & M. Curie University. She was named Research Director in 2007. Her research interests are the study of enzyme mechanisms (D-Ala-D-Ala ligase, VanB, VanX, glucosamine-6P synthase Gfat, RMS3) and the elaboration of enzyme inhibitors, at the interface between organic chemistry and biochemistry. The main guideline of the enzymes under study is the elucidation of their catalytic mechanism to design, synthesize and evaluate new inhibitors. Since 2014, she has been involved in the metabolic labeling of bacterial glycan and mammalian cellular glycan as well as in the study of strigolactone receptors.

Dr. Aurélie Baron chemical engineer of CPE Lyon (2005), obtained in 2009 her PhD in organic chemistry from the University Paris-Sud. After she did a two years postdoctoral training under the supervision of Winfried Leibl in the group of Photocatalysis and Biohydrogen (CEA Saclay, iBiTec-S). She joined the ICSN in 2012 as CDD Researcher in the team of Boris Vauzeilles. At the end of 2017, she joined the CNRS as “Ingénieure de Recherche”, within the thematic Probes and Modulators for Biological Targets, in the department of Chemical Biology of the ICSN. She works mainly in the development, the synthesis and the characterization of saccharidic derivatives and molecular tools for the metabolic labeling of glycanes.

Dr. Francois-Didier BOYER (CNRS Researcher) received a chemical engineering degree from ESPCI Paris. He obtained his Ph.D. in 1994 under the supervision of Pr. Jean-Yves Lallemand from the Ecole Polytechnique (Palaiseau, France). After one year postdoctoral training with Pr. Stephen Hanessian from the Université de Montréal, Canada, he joined the INRA (French National Institute of Agricultural Research) in 1995 at Unit for Phytopharmacy and Chemical Mediators (Versailles) in the group of Dr Descoins. He joined the group of Jean-Marie Beau at the ICSN in June 2008. His current interests concern the synthesis of natural chemical mediators involved in plant growth. He joined the CNRS in January 2020. He has been deputy coordonnator of the Department of Chemical Biology at ICSN since January 2020.

Dr. Arnaud CHEVALIER received his Ph.D. in bioorganic chemistry in 2014 at the University of Rouen under the co-supervision of Profs. Pierre-Yves Renard and Anthony Romieu. His research works have been focused on the development of new advanced chemical tools for molecular imaging applications especially fluorescence imaging. After a first postdoctoral fellow between 2014 and 2016 under the guidance of Prof. Dr. Sidney M. Hecht at the Arizona State University (United States of America). He joined Dr. Xavier Franck team for an additional post doc dedicated to total synthesis and methodology. In 2017, his last post doc fellow in the Frederic Taran Team at CEA Saclay was focused on radiolabelling and bioconjugation chemistry. Recruited in CNRS as a permanent scientist in October 2018 to wotk in collaboration with Philippe Durand in the Chemical Biology Department at ICSN UPR 2301, his workfield is primarily motivated by the discovery of new methods for the transport and delivery of drugs or imaging agents. organelles such as mitochondria or lysosome.

Dr. Stéphanie DEVILLE-FOILLARD completed a Ph.D. degree in chemistry/biology from Joseph Fourier University (Prof. P. Dumy, 2008, Grenoble), where she was trained in the field of peptide synthesis and molecular engineering. After post-doctoral trainings in nanomedicine on carbon nanotubes (Dr. E. Doris, 2008-2010, CEA Saclay), peptide self-assemblies (Dr. M. Paternostre, 2010-2012, CEA Saclay/IPSEN Les Ulis) and quantum dots (Dr. B. Dubertret, 2012-2013, ESCPI/NextDot Paris), she was appointed by the CNRS as Chargée de Recherche in the chemistry group of Curie Institute (Dr. F. Schmidt, 2013-2017, Paris). She has developed protein conjugates for cancer therapeutic delivery. In January 2017, she joined Chemical Biology Department at the ICSN to work on nanomedicines (gold nanoparticles), molecular MRI contrast agents/radioenhancers (gadolinium chelates) and peptidic/peptidomimetic approaches for medicinal chemistry.

Dr. Philippe DURAND is a CNRS researcher. He is the coordinator of Scientific Services and Platforms at the Institut de Chimie des Substances Naturelles (ICSN). He received his undergraduate degree in chemistry-biochemistry and his Ph.D. in molecular pharmacology from the Paris VI University under the supervision of Prof. François Le GOFFIC and Dr Sames SICSIC in 1985. After his military service as scientist (Percy Hospital), he joined the ISOCHEM company as chemist in 1987 (Custom synthesis) and then moved to FOURNIER company as senior scientist in medicinal chemistry and team manager in 1994 (Pharmaceutical industry). He was recruited as a CNRS research associate in 2001 at ICSN where he was named research director in 2018. His research has been concerned with bioorganic, medicinal chemistries and more recently molecular imaging and chemical biology. The major objective of his more recent research studies has been focused on the study of enzymes mechanism, their inhibition and the in vitro and in vivo detection of their activity. In the latter context, he recently developed, in close collaboration with Eva TOTH’s group (Orléans), new enzyme responsive contrast agents for MRI (T1, paraCEST) /optical imaging.

Dr. Marie-Pierre Golinelli is a CNRS Researcher (CR1). After graduating in Chemistry, she did a PhD in Biochemistry under the supervision of Dr J. Meyer (Grenoble) and started to study Fe-S proteins. After 2 years with Prof Sheila S David (U. of Utah, Fe-S protein involved in DNA repair, MutY) and 2 more years with Dr Stephen Hughes (National Cancer Institute, NIH, reverse transcriptase from retroviruses), she was recruited in 2001. She was studying aminoacyl tRNA synthetases and cellular traficking by combining biochemical approches with cellular biology. In 2013, she joined the ICSN. She looks at Fe-S proteins focusing more on the NEET family, proteins acting as redox switch in mammalian cells. Member of the SFBC, SFBBM, COST Fe-S and FrenchBIC.

Dr. Olivier GUITTET is an assistant professor at Université Paris-Saclay. Ha has gratuated in biochemistry and molecular biology before obtaining his PhD degree at université Paris-Sud under the supervision of Dr Michel Lepoivre. He focused on the regulation by nitrogen oxydes of ribonucleotide reductase (RNR), an essential player in deoxyribonucleotide precursors of DNA. He has then studied the transcriptional regualtion of RNRs in Pr Lars Thelander’s group (Umeå University, Sweden). At université Paris-Sud in Michel Lepoivre group he then worked on redox signalling, first by exploring the role of RNRs in resistance to oxidative ans nitrosative stresses, and then on the co-operation between TGF and p73 (a member of the p53 tumor suppressors family) in the regulation of inducible NO synthase expression. He has joined ICSN from 2020 where his interest is on TGF-p73 cooperation in control of redox signalling in the context of fibrotic pathologies. As an assistant professor since 2008, he teaches cell biology at the Licence and Master levels.

Dr. Meng-Er HUANG   is a Research Director at the CNRS. During his early career as hematologist in Shanghai (China), he made a key contribution to the discovery of therapeutic effect of all-trans retinoic acid in the treatment of acute promyelocytic leukemia through induction of differentiation. In 1993, he obtained a PhD degree from the Université Paris-Diderot under the supervision of Dr. Francis Galibert. After a postdoctoral training, he joined CNRS as a junior researcher in 1995. From 2002 to 2005, he worked as a visiting scientist in the laboratory of Prof. Richard Kolodner at Ludwig Institute for Cancer Research at San Diego (California). Supported by a CNRS ATIP program in 2005, he created a new research team in the Institut Curie and led the research projects for better understand oxidative stress-induced genome instability and cell death, and redox-based mechanisms of anticancer molecules. He has joined the ICSN since 2020 in order to constitute a strong group that work on several aspects of redox biology. In this new scientific environment, he is continuously focusing on exploiting oxidative stress- and redox-based anticancer therapeutic strategy in leukemia, breast and lung cancer models.

Dr. Michel LEPOIVRE is a Research Director at the CNRS. He has a strong expertise in the field of redox signaling and oxidative stress. After academic training in biochemistry and enzymology, he completed his PhD thesis in the laboratory of Jean-François Petit at the University Paris-Sud, where he studied the anti-tumor properties of activated type I macrophages in relationship with the production of reactive oxygen species by NADPH oxidase 2. After his recruitment at the CNRS in 1986, he began an in-depth investigation of the cytotoxicity of macrophage-derived nitric oxide (NO), focusing more specifically on the inhibition by NO of ribonucleotide reductase (Rnr), a crucial enzyme crucial for DNA synthesis and tumor cell replication. During this period, he also developed collaborative works with chemists to discover new nucleoside analogues inhibiting Rnr, a pharmacological target for anti-cancer and anti-viral treatments. Appointed Research Director in 1997, he began to manage a research team at Paris-Sud University in 2005. Since 2009, he has been interested in the functional interactions between NO and p73, one of the three members of the p53 suppressor family. In particular, he unveiled a synergy between p73 and TGF-β in the downregulation of the NOS2 gene encoding inducible NO synthase in fibroblasts. In 2020, he joined ICSN to study the role of p73 in the production of reactive oxygen species dependent on the TGF-β signaling pathway and involved in fibrotic pathologies.

Dr. Stephanie NORSIKIAN received a Ph.D. degree from the Université of Paris VI in 1999, under the supervision of Prof. J.-F. Normant. After post-doctoral trainings in the groups of Prof. D.M. Hodgson (Oxford, U.K), Prof. G. Guillaumet (Orléans, France) and Prof. H. Kagan (Orsay, France), she was appointed by the CNRS as Chargée de Recherche in 2002 in the group of Prof. A. Lubineau. In January 2007, she joined Prof. J.-M. Beau’s group at the ICSN.

Dr. Boris VAUZEILLES is a CNRS researcher (Senior Researcher). He is the director of the Institut de Chimie des Substances Naturelles (ICSN) in Gif-sur-Yvette. As a student, he joined the Ecole Normale Supérieure in 1990, where he obtained in 1996 a PhD degree from Université Pierre et Marie Curie, under the supervision of Prof. Pierre Sinaÿ. He then moved to Cambridge, Massachussets, for a post-doctoral stay at MIT with Prof. Julius Rebek, Jr, and followed the group, which soon relocated to the Scripps Research Institute in La Jolla (California). He joined CNRS as a researcher in 1998, in the group of Prof. Jean-Marie Beau in Orsay (Institut de Chimie Moléculaire et des Matériaux d’Orsay (ICMMO), Université Paris-Sud). In 2006 he became the leader of a small group focusing on Glycomimetics and Recognition. In 2012 he was offered the opportunity to create, in parallel with this activity in Orsay, a new team at ICSN. At the end of 2014 he became the co-founder of a startup company, Click4Tag. His research interests focus on the application of synthetic chemistry to the development of molecular probes to investigate biological processes. This includes synthetic glycochemistry and the synthesis of bioactive carbohydrate analogues and glycoconjugates, the development of eco-friendly chemistry using biomass as a starting material, studies towards artificial photosynthesis, as well as metabolic glycan labeling of living bacteria.

He is the Director of the ICSN since early 2020.

Dr. Laurence VERNIS is a Research Scientist at INSERM. She received a Master Degree in Agricultural Sciences from the National Institute for Agricultural Sciences (INAPG) together with Paris Sud University, and received her PhD in microbiology on the study of autonomously replicating plasmids in the dimorphic yeast Yarrowia lipolytica. After two post-doctoral positions working on secretion and DNA replication using various yeast models, she was appointed  by INSERM at the Institut Curie in Orsay, focusing on DNA replication and genomic instability. In 2020, she joined ICSN to study redox regulations of genomic instability in a dedicated scientific environment.

Dr. Sébastien VIDAL received his PhD in organic chemistry in 2000 (University of Montpellier, France – Prof. Jean-Louis Montero and Prof. Alain Morère) on the synthesis of mannose 6-phosphate analogues. He then moved to UCLA with Sir J. Fraser Stoddart (Nobel Prize in Chemistry 2016) to study glycodendrimers. In 2003, he joined NREL (Golden, Colorado) with Prof Joseph Bozell and studied the combination of organometallic and carbohydrate chemistries. He obtained a CNRS position at University of Lyon in 2004 and started his own projects on carbohydrate chemistry and applications in biology. He has now joined the Institut de Chimie des Substances Naturelles.

PhD Students and Postdoc Researchers

Wanatsaya ATWICHAI has obtained her Master’s degree in Pharmaceutical Chemistry from Paris-Saclay University (Faculty of Pharmacy, Paris-Sud University) in 2019. Since January 2020, she is a PhD student at the ICSN, supervised by Dr. Boris Vauzeilles and Dr. Aurelie Baron. Her subject is “Sialic acids engineering as a strategy for alternative antibacterial discovery”.

Suzanne DAIGNAN FORNIER de LACHAUX has obtained in 2019 her diploma from ENSIACET (Ecole Nationale Supérieure des Ingénieurs en Arts Chimiques Et Technologiques) in Toulouse. She is a PhD student at the ICSN, supervised by Dr. François-Didier Boyer. Her subject is “Hemp strigolactone synthesis, development of marked standards for its quantification in hemp exudates or in planta “.

Dr. Minh-Duc HOANG obtained his PhD in organic chemistry with a specialized field of nanomedicine and catalysis in 2019 under the supervision of Dr. Edmond Gravel and Dr. Eric Doris. His research focused on the study of nanostructures (spherical micelles and double-layer ribbons) obtained by self-assemblies of polymerizable diacetylene amphiphiles. In January 2020, Minh Duc joined the Institute for Chemistry of Natural Substances as a postdoctoral researcher in the Department of Chemical Biology. He works on developing new fluorescent compounds intended for biomedical applications under the supervision of Dr. Arnaud Chevalier and Dr. Philippe Durand.

Silva KHODJOYAN has obtained her Master’s degree in ”Sciences, Technologies, Health, Chemistry” in 2019 with a major in Molecular Chemistry at Sorbonne University. She has started as PhD student at the ICSN since January 2020, supervised by Dr Christina Sizun and co-supervised by Dr Philippe Durand. Currently she is working on the design of antiviral drugs for bronchiolitis virus using novel therapeutic target.

Coordonnator : Marie-Pierre GOLINELLI

Deputy Coordonnator : François-Didier BOYER

Department thematics

Probes and Modulators for Biological Targets
(B. Badet, M.-A. Badet-Denisot, A. Baron, J.-M. Beau, F.-D. Boyer, S. Deville, P. Durand, S. Norsikian, B. Vauzeilles, S. Vidal)

Oxidative Stress, Iron-Sulfur Proteins and Cancer
(M.-P. Golinelli, O. Guittet, M.-E. Huang, M. Lepoivre, S. Riquier, L. Vernis)

Plateforme CIBI : Criblage de composés bio-actifs
(J. Bignon, H. Levaique)