The group uses molecular chemistry, chemical biology and biophysical chemistry to design responsive (supra)molecular tools to visualize and study biological processes with a strong emphasis on the development of fluorescent probes for bioimaging. ![](https://chimiex.rubidiumweb.fr/assets/b3d765ec-7fb1-40fd-b665-ab61f4df186e) ### Chemogenetic probes and sensors to visualize cellular biochemistry Hybrid chemogenetic probes associating a genetically-encoded protein and a small molecular probe are a versatile approach for bioimaging that combine the selectivity of the genetic encoding with the flexibility of organic fluorophore design. Using the HaloTag technology, we have design a series of fluorogenic probes based on dipolar molecular rotors. These small molecules combine ease of synthesis, wavelength tunability, and strong fluorescence activation in presence of the HaloTag protein allowing wash-free imaging of subcellular organelles in live cells.^\[1-4\] We then adapted these fluorogenic scaffolds to yield genetically targeted sensors for subcellular calcium imaging and to follow protein exocytosis.^\[5-6\] Ongoing projects involve the development of Zn²⁺ and redox fluorescent sensors.^\[7\] We are also interested in the design of red-shifted bioluminescent reporters as an alternative to fluorescence imaging. **References:** \[1\] S. Bachollet, C. Addi, N. Pietrancosta, J.-M. M. Mallet, B. Dumat, _Chem. - A Eur. J._ **2020**, _26_, 14467-14473. \[2\] S. Bachollet, Y. Shpinov, F. Broch, H. Benaissa, A. Gautier, N. Pietrancosta, J.-M. Mallet, B. Dumat, _Org. Biomol. Chem._ **2022**, _20_, 3619-3628. \[3\] J. Coïs, S. Bachollet, L. Sanchez, N. Pietrancosta, V. Vialou, J. M. Mallet, B. Dumat, _Chem. - A Eur. J._ **2024**, _30_, e202400641. \[4\] B. Dumat, C. Chieffo, _Chem. - A Eur. J._ **2025**, _31_, e202404077. \[5\] S. Bachollet, N. Pietrancosta, J.-M. Mallet, B. Dumat, _Chem. Commun._ **2022**, _58_, 6594-6597. \[6\] J. Coïs, M.-L. Niepon, M. Wittwer, H. Sepasi Tehrani, P. Bun, J.-M. Mallet, V. Vialou, B. Dumat, _ACS Sensors_ **2024**, _9_, 4690-4700. \[7\] M. Čížková, L. Cattiaux, J. Pandard, M. Guille-Collignon, F. Lemaître, J. Delacotte, J.-M. Mallet, E. Labbé, O. Buriez, _Electrochem. commun._ **2018**, _97_, 46-50. ### Biomimetic functionalized lipid microparticles to study phagocytosis Phagocytosis is fundamental process of innate immunity by which phagocytic cells (_e.g._ macrophages) internalize objects larger than 0.5 microns. To study its mechanism, we have designed oil-in-water emulsion droplets of micrometric size funtionnalized with tailor-made fluorescent (glyco)lipids to target lectin receptors and report on the cellular adhesion^\[8\] or subsequent pH acidification during phagosome maturation.^\[9\] Ongoing projects are aimed at further investigating enzymatic activity and recycling during the late stages of phagocytosis. **References:** \[8\] S. Michelis, C. Pompili, F. Niedergang, J. Fattaccioli, B. Dumat, J.-M. Mallet, _ACS Appl. Mater. Interfaces_ **2024**, _16_, 9669-9679. \[9\] S. MichelisH ; Uhl, F. Niedergang, J. Fattaccioli, B. Dumat, J.-M. Mallet _BiorXiv_ **2026**, 11.20.685382 ### Functionalized Polysaccharides for biological applications Polysaccharides are natural polymers, an excellent alternative to synthetic polymers. Many are commercially available (in various sizes and functions) and, thanks to their hydrophilic properties, are particularly well-suited to biological applications. We have developed modified polysaccharides for coating particles: gold nanoparticles (in collaboration with F. Carn), Mil-100 iron nanoparticles (in collaboration with C. Serre and M. Lepoitevin), and for presenting multivalent antigens (in collaboration with Anna Maria Papini and Laurence Mulard). We are also preparing dextran-based micro- and nanoparticles for the development of a vaccine targeting Shigella flexneri (in collaboration with Laurence Mulard, Institut Pasteur). Cyclodextrins are cyclic oligosaccharides known to form host-guest complexes; we use them to prepare self-assembled nanogels (collaboration with K. Bouchemal). **References:** **Selective capture of anti-N-glucosylated NTHi adhesin peptide antibodies by a multivalent dextran conjugate**; Antonio Mazzoleni, Feliciana Real Fernandez, Francesca Nuti, Roberta Lanzillo, Vincenzo Brescia Morra, Paolo Dambruoso, Monica Bertoldo, Paolo Rovero, Jean-Maurice Mallet, Anna Maria Papini _Chembiochem_ **2022**, 23, 2022 e202100515 . doi :10.1002/cbic.202100515 **Flash Colloidal Assembly in Micro Flow System** Florent Voisin, Gerald Lelong, Jean-Michel Guigner, Thomas Bizien, Jean-Maurice Mallet, Florent Carn, _ACS Appl. Nano Mater._ **2022**, 5, 5, 6964-6971. doi. /10.1021/acsanm.2c00944 **Charge-Driven Arrested Phase-Separation of Polyelectrolyte-Gold Nanoparticle Assemblies Leading to Plasmonic Oligomers;** Florent Voisin, Gerald Lelong, Jean-Michel Guigner, Thomas Bizien, Jean-Maurice Mallet, Florent Carn, _Journal of Colloid and Interface Science, 630,_ **2023**_, 355-364_, doi 10.1016/j.jcis.2022.08.076 **Self-assembly of gold nanoparticles by chitosan for improved epinephrine detection using a portable surface enhanced Raman scattering device** Antoine Dowek, Florent Voisin, Laetitia Le, Céline Tan, Jean-Maurice Mallet, Florent Carn, Eric Caudron _Talanta_ **2023**, 251, 123752; _doi_ /j.talanta.2022.123752 **Cyclodextrin-based supramolecular nanogels decorated with mannose for short peptide encapsulation** Archana Sumohan Pillai, Mohamed Achraf Ben Njima, Yasmine Ayadi, Laurent Cattiaux, Ali Ladram, Christophe Piesse, Benoit Baptiste, Jean-François Gallard, Jean-Maurice Mallet, Kawthar Bouchemal _International Journal of Pharmaceutics_, 2024 DOI:10.1016/j.ijpharm.2024.124379 ### Chemical neurosciences The **Chemical Neurosciences** thematic develops an integrated chemical biology approach to decipher and modulate synaptic mechanisms at the molecular level. It combines **rational ligand design, molecular modeling and protein-protein interaction analysis** with advanced fluorescence imaging to target key synaptic proteins. Major achievements include the **first drug-like ligands of vesicular glutamate transporters (VGLUTs)**, enabling selective modulation of glutamatergic transmission from biochemistry to in vivo behavior. We also highlight that **flexible and dynamic protein-protein interfaces**, such as dopamine-NMDA receptor heteromers, can be **pharmacologically targeted**, overturning the concept of "undruggable" synaptic complexes. Together, these results provide **innovative molecular tools and therapeutic perspectives** for neurological and psychiatric disorders. ![](https://chimiex.rubidiumweb.fr/assets/d5b7eb00-1b39-4abd-be43-8eb4c4f2001c)

Nicolas BIRLIRAKIS

Nicolas BIRLIRAKIS