[Dec. 20, 2024] Happy to end this year with an invited article now published in ChemMedChem, which supports the Société de Chimie Thérapeutique (SCT) through the Special Collection "Drug Discovery in France" edited by Rebecca Deprez-Poulain (University of Lille), Maria Duca (University of Côte d'Azur) and Gilles Guichard (University of Bordeaux). We thus took this opportunity to describe a series of investigations carried out in collaboration with Petra Menova (University of Chemistry and Technology, Prague, CZ), Gabor Paragi (Institute of Physics, University of Pécs, HU; Department of Theoretical Physics, University of Szeged, HU) and Nicolas Chéron (PASTEUR, Département de chimie, ENS Paris, FR). We aimed at uncovering the mechanism behind the exquisite photophysical properties of N-TASQ, a twice-as-smart G4 probe that allows for tracking RNA G4s in live cells. We reported on the synthesis and in vitro studies of AlkN-TASQ and TzN-TASQ, which provides very interesting insights into the way through which N-TASQ derivatives label G4s. Thrilling!
[Dec. 11, 2024] Jérémie spent the last months (to say the least :-)) to make the G4RP protocol fully reliable and reproducible. To this end, each step of the 1st version (published in Nat. Commun. in 2018, and in Nat. Protoc. in 2022) developped with Judy and Sunny was optimized, and he added a series of control and go/no-go steps. This new version, G4RP.v2 is now published in STAR Protocols: more than 40 steps, over more than 40 pages, impossible not to be succesful now! Congrats Jérem!
[Nov. 29, 2024] Certainly one of the ones I am most proud of. In this J. Biol. Chem. article, we carried out a real chemical biology investigation in which we positively and negatively modulate the G4 landscape in patient-derived human astrocytes, using the G4 ligand PDS and the molecular helicase PhpC, respectively. This allowed us for assessing the cellular consequences at both transcription and translation levels by RNA-seq and proteomics, respectively, and drawing a series of conclusions concerning 1/ the actual regulatory roles of G4s, and 2/ the actual influence of both molecular tools in human cells. A long-term and absolutely thrilling scientific adventure.. congrats to all co-authors!
[Oct. 24, 2024] Extremely honored to have been interviewed by the CNRS to freely speak about G4s, my feelings and thoughts about the G4-focused research, the achievements and futur challenges, notably in the field of age-related diseases. Part of the interview (text) here: https://www.centre-est.cnrs.fr/fr/lumiere-sur-les-quadruplexes-dadn; the complete interview (audio, 25 min) here: https://youtu.be/NbVgqAKaRsg?list=PLWbM_xdKU4muTdpg5JA5OSemiL72XXI-Q (sorry, only in French)
[Oct. 15, 2024] Quite happy that the CNRS decided to highlight the results we recently published in Angew. Chem. Int. Ed. in which we showed that three-way DNA junctions (TWJs) are promising targets for anticancer therapeutic intervention and that azacryptands are specific TWJ ligands, meaning promising anticancer agents. The highlight can be found here (sorry, only in French)
[Sep. 17, 2024] Thank you so much Sara (Sara Richter, University of Padua, IT) for associating me to a beautiful study aiming at understanding the molecular basis of X-linked dystonia Parkinsonism (XDP). This study, now published in Nucleic Acids Res. aims at understaning the role that G4s play in the regulation of the expression of TAF1 gene (dysregulated in XDP), and how it is possible to modulate its expression using our G4 unfolder PhpC. A small contribution to a brilliant and thrilling study!
[Sep. 16, 2024] Quite honored to appear in this prestigious list for the fourth year in a row (https://dx.doi.org/10.17632/btchxktzyw.7). It does not mean much in terms of science per se but I am just thrilled to be there, which is some sort of peer recognition of the determination and tireless work done by my team and colleagues in a not-often-easy national and international context. Thanks to all of them!
[Sep. 7, 2024] It was an honor for me to be invited to contribute to a special issue of Med. Chem. Res. honoring Prof. Stephen Neidle: I took this opportunity to retrace his carreer and highlights his most significant contributions to the field, from the publication of the very first G4 ligand in 1997 to the recent clinical investigations of his latest ligand QN302. This contribution is a personnal view on this fascinating scientific story (might be biased, admittedly) but I really enjoyed writing it!
[Aug. 21, 2024] In the framework of our ongoing (and long-lasting) collaboration with Jun Zhou (Nanjing U., PRC), we keep on investigating the power of G4-based catalysis. In this novel Anal. Chem. article, we chemically modified the cofactor hemin to recreate (somehow) its binding site within its natural proteinic partner HRP to increase the catalytic efficiency of the G4/hemin complex. The validity of this apporach was confirmed through the development of a colorimetric assay for the detection of FEN1 enzyme.
[July 04, 2024] We are quite happy that our Top2G4 project ("understanding and tuning the cellular properties of G4 ligands") has been funded by the ANR. This project is steered by Sébastion Britton (IPBS Toulouse, FR), in collaboration with Valerie lamour (IGBMC Strasbourg, FR). We will investigate the mechanism(s) behind the cellular properties of G4 ligands in the aim of rationalizing the differences between standards in the filed (PDS, PhenDC3, CX5461, etc.). Thanks Sébastien for your efforts in gathering this wonderful consortium and desiging this beautiful project!
[June 25, 2024] In this Angew. Chem. article, we not only describe an array of highly promising ligands for three-way DNA junctions (TWJs) from the azacryptand series but also a panel of techniques to investigate their TWJ-interacting properties in vitro but also their ability to stall DNA transactions, therefore moving closed to predictive models for cellular investigations. Another great collaboration with my 'TWJ dream team'': Anton Granzhan (Curie Orsay, FR), Sébastien Britton (IPBS Toulouse, FR), Nicolas Chéron (Pasteur Paris, FR) and Lukas Trantirek (CEITEC, CZ).
[June 25, 2024] In this article now published in Adv. Sci., we report on a supramolecular nanomaterial (referred to as AA-heminzyme) which is prepared in a straightforward manner (a kind of mix-and-measure approach) and is used for performing catalytic oxidation reactions. Its practical use was demonstrated by the smartphone-based detection of a circulating cancer biomarker.. thrilling! Another great collaboration with Dr. Jun Zhou (Nanjing U. PRC).
[June 21, 2024] The time is ripe to gather the community of researchers working on DNA junctions under a single banner... and CNRS Chimie gives us this possibility! Thanks to quite interesting discussions with Mike Hannon and Mark Searcey (Birmingham and Norwich UK) on one side, and Miguel Vazquez Lopez and Eugenio Vazquez (Santiago di Compostela, ES), we are poised to create an IRN on DNA and RNA junctions in order to 1/ optimize the connection between the different European partners on the basis of the complementarity of their expertise, 2/ secure an optimized scientific workflow between them from chemistry to biology, through in silico and structural studies, and 3/ coordinate this research effort thanks to a dedicated budget used for organizing workshops, student exchange and visiting professorship programs.
[June 19, 2024] An i-motif (iM) is a four-stranded (quadruplex) DNA/RNA structure that folds from cytosine (C)-rich sequences. These peculiar structures are thought to play key roles in various DNA transactions but which ones?? In this review now published in Trends Genet., we sum up the techniques applied to assess the folding of iMs in vitro and the factors that affect their formation and stability in vivo in a comprehensive manner. A great collaboration with Dr. Wenli Zhang (Nanjing U. PRC).
[June 06, 2024] We would like to sincerely thank CNRS innovation for funding the MoBiDic project (for Molecular, Biomimetic probes for the Diagnosis of Cancers) which will also us to keep on developing new TASQs for whole-body applications (small animals). These new investigations will thus provide us with the opportunity to expand our TASQ portfolio for new applications in oncology (nuclear imaging).
[May 27, 2024] We are really happy to announce that Garance Psalmon, currently in M2 internship in the lab, has successfully passed a quite challenging examination to obtain a PhD grant (funded by the Conseil Regional de Bourgogne, CRB) for the next 3 years in the GATTACA Lab. She will work on the biology of DNA and RNA G4s, modulating their formation in cells using both stabilizers and destabilizers. Very happy to have her in the lab for 3 more years!
[March 12, 2024] It is a huge honour to have been promoted to the rank of CNRS Research Director 1st class (I am therefore a quite old researcher by now, and officially :-)). Of course, without would have been possible without talented students and wonderful collaborators. Many thanks to all of them!
[Feb. 21, 2024] Quite happy to be associated to a beautiful study steered by Stefania Millevoi (CRCT Toulouse, FR) that shows how RNA G-quadruplexes (G4s) regulate mitochondrial mRNA translation and how G4 ligands modulate mitochondrial functions in cancer cells, thus providing a functional link between G4s and energy metabolism. Now available here: https://www.biorxiv.org/content/10.1101/2024.01.29.577192v1. And quite happy too to collaborate once more with Andrey S. Tsvetkov (UTHealth, Houston, TX USA) to perform a study in the best traditions of chemical biology in which we either positively (or stabilize) or negatively regulate (or destabilize) G4s in human astrocytes in order to gain insights into the prevalence of G4-mediated cellular circuitries in brain cells. Now available here: https://www.biorxiv.org/content/10.1101/2024.02.16.580621v1.
[Jan. 23, 2024] Quite honored and proud to have been interviewed by the CNRS about the results we recently reported in ChemComm. The question was about the potential application of these discoveries, which are quite huge for both fundamental and applied research. We discussed about G-quadruplex-DNA (quite unsurprisingly) but also cancers, aging and to potential use of our prototype of G4 destabilizer PhpC (see the original article here). The article can be found here, the interview here (sorry, only in French)