2020

A beautiful way to end a year..

[Dec. 21, 2020] .. that continues to be an unprecedented and extraordinarily difficult year. Thanks to a fully dedicated team (Jo & Pauline, Francesco & Jérémie), supported by a CNRS colleague, Ibai, whose help has been invaluable to tackle the very complicated TASQ chemistry, we are proud to end the year with this new preprint deposited in bioRxiv that describes new bioinylated TASQs and their use as molecular baits to fish G4s out of human cells and tools for visualizing G4s in cells thanks to a new pre-targeted optical imaging strategy. Thanks you all, enjoy the end-of-the-year break and.. keep safe!

After all these years in Bourgogne..

[Nov. 26, 2020] .. I am so happy to be finally associated to a study on the beneficial effects of the red wine.. Happiness! ;-) Thanks to Dominique Delmas and his team for the work entitled "Red wine extract inhibits VEGF secretion and its signalling pathway in retinal ARPE-19 cells to potentially disrupt AMD" (AMD for Age-Related Macular Degeneration) now accepted for publication in Molecules, as part of the Special Issue "Benefits of the Mediterranean Diet–Wine Association".

We found it!

[Nov. 17, 2020] The actual goal of the ANR project DEMENTIA (2017-2020) was to identify small-molecules able to disrupt or unfold G-quadruplexes (G4s) as a way to rescue helicase deficiencies (at the origin of many human diseases, cf Brosh & Matson) and/or to counteract aberrant G4 landscapes. This was a rather complicated project, mostly due to the lack of reliable assays to assess accurately the G4-disrupting properties of putative candidates. To tackle this issue, over the past 3 years we have invested massive efforts to develop the G4-Unfold assay and then used it to identify a series of molecules with promising properties. The results of this long-term commitment, and collaborative work with Anton Granzhan (Institut Curie, Orsay, FR), Jean-Baptiste Boulé (MNHN, Paris, FR) and Robert Hudson (Western University, Ontario, CA), have now been posted on bioRxiv. The best is yet to come!

A new article in CCS Chem

[Oct. 1, 2020] CCS chem. is a journal of the Chinese Chemical Society launched in March 2019, aimed at becoming soon a flagship journal of chemistry. We are delighted to have our new collaborative study (Nanjing, Amsterdam, Dijon) now accepted for publication in CCS Chem. Here, we combined experimental and theoretical approaches to fine-tune the electronic properties of the hemin binding site within a quadruplex (G4) architecture, in order to improve the catalytic properties of the resulting quadruplex/hemin system (referred to as G4-DNAzyme). Congrats to all authors for this multi-country project and truly interdisciplinary study!

NIH Granted!

[Sept. 24, 2020] It’s a great pleasure and an immense honor to be associated to a project steered by Andrey S. Tsvetkov in collaboration with Aki Urayama, Sean Marrelli and Louise D. McCullough at UThealth, McGovern Medical School (TX, USA) now granted by the NIH NIA (National Institute on Aging). This project investigates the G-quadruplex (G4) DNA pathway in senescence of neurovascular unit (NVU) in the brain. The major goal is to understand if stabilization of G4s leads to senescence of the components of the NVU - endothelial cells, astrocytes, neurons, and pericytes, with straightforward applications in the field of neurodegenerative diseases.

Our review on DNA damage, repair and alternative DNA structures now published in RSC Chem. Biol.

[Sept. 20, 2020] We are delighted to have our huge review -31 page-long, 425 references- is now accepted for publication in the novel RSC journal, RSC Chem. Biol. We have invested massive efforts to portray the fields of DNA damage and DNA repair in their true colors and to show how the considerable body of research accumulated over the past years offer brand new therapeutic opportunities. Then, we introduced alternative DNA structures (G-quadruplexes, DNA junctions) and show how they represent a promising class of targets for cancer therapy via the DNA damage response circuitry, thus merging research areas that, traditionally, do not overlap. We sincerely hope that this comprehensive review will help researchers from different fields enter what could be reasonably regarded as one of the most fascinating chemical biology adventures. Congrats to Jo, Francesco and Séb!

Webinar series 2020 on Nucleic Acid Secondary Structures

[July 20, 2020] Thrilled to be invited to talk about our recent results during the Webinar series 2020 on « Nucleic acid secondary structures: G4s and beyond » organized jointly by Sara Richter and Katrin Paeschke. After a first series between June and July 2020, the second series will take place this fall (strating on Sept. 3, 2020), following the same principle: on-line, free access, 1 hour per week (usually Thursday, 2 pm CEST), 2 speakers per session.. quite convenient! More info? Please contact Sara and Katrin at G4webinarseries@gmail.com

A new article in Chemical Science

[July 16, 2020] Delighted to work with Prof. Can Li and his team to keep on investigating the potential of catalytic G-quadruplex (G4)-DNA, referred to as G4-DNAzyme, through a series of experiments in which the catalytic activity of G4-DNAzymes is drastically enhanced by a non-covalent dimerization of G4s around the hemin cofactor. Many thanks to Yu and Minpang for their very hard and multidisciplinary work, which validates the use of G4s as as biosourced tools to oxidize organic pollutants from anthropogenic origins. The corresponding article is now accepted for publication in Chemical Science.

The first GATTACA’s Autophagy article

[May 18, 2020] We keep on investigating the roles that G-quadruplexes (G4s) might play in neurobiology. Thanks again to our collaboration with Andrey Tsvetkov (McGovern Medical School, The University of Texas at Houston (UTHealth), USA), we now demonstrate that G4s regulate of the autophagy in both neurons and astrocytes. These results, now published in Autophagy, lend further credence to the fact that G4s might represent an epigenetic-like mechanism that regualtes gene expression in central nervous system cells. Congrats to all coauthors!

Quadruplex nucleic acids as targets for medicinal chemistry

[May 4, 2020] Honored to have been invited to contribute to the forthcoming issue of Annu. Rep. Med. Chem. entitled "Quadruplex nucleic acids as taregts for medicinal chemistry", edited by S. Neidle, and to be co-listed with a prestigious series of authors including L. H. Hurley (USA), F. B. Johnson (USA), A. T. Phan (SG), H. Sugiyama (JP), S. Richter (IT), J.-L. Mergny (FR), F. Doria (IT), J. Sponer (CZ), M.-P. Teulade-Fichou (FR), J. Dash (IN), L. E. Xodo (IT), J. S. Schneekloth (USA), C. Sissi (IT), J. Plavec (SI) and R. Vilar (UK). My contribution, entitled "Quadruplex detection in human cells", is dedicated to the molecular probes (organic dyes, antibodies, etc.) recently developped and used for tracking DNA and RNA quadruplexes in cells.

Media coverage for our eLife article : print media & radio broadcast

[Feb. 14, 2020] Really happy that our publication in eLife has generated enthusiasm, being relayed by the CNRS, Recherche uB and offered me the possibility of being interviewed by Adrien Zerbini for the radio broadcast CQFD of the RTS (Radio Télévision Suisse). A great experience !

See also the description (in French) of our article in Sciences & Avenir and in Pour La Science.

The first GATTACA’s eLife article

[Jan. 8, 2020] G-quadruplexes (G4s) will now find tremendous applications in neurobiology! Thanks to our collaboration with Andrey Tsvetkov (McGovern Medical School, The University of Texas at Houston (UTHealth), USA), we now demonstrate that G4s are key players in the regulation of the neuronal autophagy. In a manuscript now accepted for publication in eLife, we show that G4 landscapes are modulated with aging, we describe a novel pathway for regulating autophagy in neurons (via a G4-mediated regulation of Atg7 gene expression) and provide new therapeutic possibilities to fight against age-related genetic dysregulations and diseases. Congrats to all coauthors!

A new article in ChemComm

[Jan. 6, 2020] Thanks to our ongoing collaborative efforts with Jun Zhou, at the University of Nanjing (China), we keep on delving into the fine mechanistic details of G-quadruplex (G4)-mediated catalysis, often referred to as G4-DNAzyme. In this news ChemComm article, we study the aftermaths of G4 oxidation on its catalytic activity, which leads to a decrease of the G4 stability and of hemin affinity as well as to a modification of the nature of the hemin binding pocket. Our results also provide invaluable insights into the actual G4-DNAzyme mechanism, favoring a guanine-flipping model that is close to what has been recently demonstrated as a naturally-occurring intermediate of G4-resolving helicase. Congrats to all coauthors!