News

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A novel article in Angew. Chem. Int. Ed.

[June 25, 2024] In this Angew. Chem. article, we not only described 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).


An article in Advanced Science

[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).


Thanks to CNRS Chimie for supporting the creation of an International Research Network (IRN)

[June 21, 2024] The time is ripe to gather the community of researchers working on DNA junctions under a single banner... and CHRS 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.   


An review in Trends in Genetics on i-motifs

[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).


Thanks to CNRS Innovation for funding the MoBiDiC project

[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).


Congrats to Garance for securing her PhD in the lab!

[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!   


Promoted

[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!


Two new bioRxiv preprints now available 

[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


Our ChemComm article highlighted by the CNRS 

[Jan. 23, 2024] Quite honored and proub 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)


How to unfold G4s in human cells? The answer is in Chemical Communications 

[Dec. 05, 2023] Just a few days before the PhD defense of Jeremie, his article on the cellular properties of the G4-destabilizer PhpC has now been published in ChemComm! We provide here two demonstrations that PhpC, the prototype of G4 unfolder we discovered a couple of years ago, does indeed unwind G4s in cells, through both optical imaging (using N-TASQ) and G4RP method (using BioCyTASQ and derivatives). Super happy for Jérémie and congrats to all the team!


A novel article in Nature Communications

[Oct. 26, 2023] The question of the day is: what is going in our cells on upon UV-irradiation (e.g., sun exposure)? Or, better put, what are the systems developed by our cells to insure genome stability? In this noveal article published in Nat. Commun., Katrin Paeschke and her team show that upon UV irradiation, DNA G-quadruplexes (or G4s) rapidly accumulate in cells, which leads to the recruitment of ZRF1, a protein involved in gene activation, senescence and cancer progression. ZRF1 binds genome-wide to G4 sites where it prevents genome instability and orchestrate DNA repair. ZRF1 is thus the first protein that positively influences a repair process by binding to G4s. These amazing, compelling study was steered by the Paeschke lab (at the University of Bonn, DE), and I am proud to be (modestly) part of it. Congrats to all co-authors and thanks to Katrin for assciotaing me to this wonderful study.  

Here we go!!

[Sep. 11, 2023After months of restoration work, our new biophys lab is ENFIN! ready. This new room (B-108) is located closed to the cell culture lab (the room next door, B-107) and is adjoining a new open-space office (B-109). 

This new work space welcomes  conditions sepctrometers (JASCO (2x) and CalrioStar (BMG Labtech), BLI (Octet), qPCR (Mx3005P), CD (JASCO) among others, and provides researchers with a lot of available benches (something that was cruelly missing in our previous labs). 

Happy to start the new acadmic year in such conditions!

An article in J. Biol Chem. 

[Aug. 8, 2023] A couple of years ago, we showed in eLife, in collaboration with Andrey S. Tsvetkov (McGovern Medical School, The university of Texas, USA) that caution must be exercised when using the G4 ligand pyridostatin (PDS) as an anticancer agent as it damages central nervous system (CNS) cells, primarily neurons. This has thus to be considered as a serious negative consequence of a G4-targeting antitumoral strategy. We now report on the mechanism behind the neuron damaging properties of PDS: thanks to a transcriptome-wide analysis, we show in J. Biol. Chem. that PDS heavily modulates the transcriptional activity of neurons (the expression of ca. 900 genes being affected), notably upregulating the Pirh2 gene, which triggers double-strand breaks (DSBs). The multi-step mechanism of DNA damage we highlight here underlines the complexity of DNA maintenance in neurons. Congrats to all co-authors! 



The Handbook of Chemical Biology of Nucleic Acids 

[Aug. 3, 2023] This handbook is a gigantic book fully devoted to the field of nucleic acids, with 90 chapters distributed in 10 categories (Physical chemistry, Structural chemistry, Organic chemistry & Ligand chemistry in Volume I; Gene expression, Analytical methods and applications & Nanotechnology in Volume II; Therapeutics, Biotechnology and synthetic biology & Functional nucleic acids in Volume III) for a total of >2800 pages! Many thanks to the Editor, Naoki Sugimoto, and the Associate Editors (C. Burrows, K. Fox, P. Herdewijn, J. Plavec, E. Rozners, K. Seley-Radtke, M-P. Teulade-Fichou, R. Winter and Z. Xi) for gathering such a knowledge! The book can be found here: https://doi.org/10.1007/978-981-19-9776-1; our contribution here: https://doi.org/10.1007/978-981-19-9776-1_37



The first Youtube video of GATTACA! 

[July 26, 2023] Many thanks to the STS Department at Bordeaux University for sharing the lecture I gave last May on-line, this is my very first Youtube video ;-)  



An article in Biochimie (special issue "Last Year at Marienbad" edited by J.-L. Mergny)

[July 20, 2023] Last year at Marienbad was organized the 8th international meeting on quadruplex nucleic acids. Jean-Louis Mergny thus decided to set up a special issue in Biochimie, gathering some of the results presented there. We are particularly happy to publish in this SI a study steered by Jean-Pierre Perreault (Sherbrooke, CA) in which our G4RP-seq technique was combined with their G4RNA Screener pipeline in order to identify RNA G4-forming sequences in glioblastoma cells. This approach, based on seq-based techniques, bioinformatic tools and biophysical assays provided a rigorous way to identify RNA G4s with a high reliability and accuracy. These results are now published in Biochimie


A novel article in ACS Catal.

[July 11, 2023] When dealing with G4-based biocatalysts, or G4-DNAzyme, it is well-known in the field that controlling the G4 topology means controlling its biocatalytic properties. In this new study, now published in ACS Catalysis, we combined experimental and theoretical investigations to control the overall topology of a G4 embedding it in a Holliday junction (HJ)-based suprastructure. By doing so, the nature and length of the HJ allow for defining the orientation of the G4 strands, which then impacts its biocatalytic properties. A compelling study steered by Jun Zhou (Nanjing Univ., PRC).


An article in Nucleic Acids Res.

[July 6, 2023] The helicase BLM is known for quite a long time to bind to and unfold DNA G4s. In this new study, now published in Nucleic Acids Res., performed in collaboration with Eran Hornstein's lab, at the Weizmann Institute of Science, Rehovot (Israel), we not only show that BLM binds to and unfold RNA G4s, but also that it is involved in the regulation of stress granule (SG) formation. Congrats to Yehuda Danino, a PhD student of Eran, who brilliantly conducted this project from A to Z!


An article in Advanced Healthcare Materials

[July 5, 2023] We are really happy to be involved in a strongly multidisciplinary study aiming at exploiting the various facets of the G4 field. In this study, we conjugated a G4-containing aptamer (AS1411) to a nanoparticle (upconverted metal-organic framework, or UMOF) to exploit successively the tumor-targeting ability of AS1411 and then its catalytic properties upon interaction with hemin (G4/hemin complex, or GH). This allowed for benefitting from the high H2O2 concentration in hypoxic tumors to produce O2 in situ, which is then converted into reactive oxygen species (ROS) thanks to the UMOF in virtue of its photodynamic therapy (PDT) properties upon irradiation at 980 nm. Complicated, hein? :-) It's then better to read the manuscript now published in Adv. Healthc. Mat. :-)

Our new workspace is almost ready

[July 4, 2023After a couple of weeks of intensive works, our new lab and office are now ready to be used. This is going to be an open space for biophysics, gathering all our machines in a specially dedicated lab. Impatient of being there!

A novel article in RSC Chem. Biol.

[July 4, 2023] We investigate here the scope of application of two new TASQ prototypes, the clickable TASQs referred to as MultiTASQ (for copper click chem, or CuAAC; commercially available at Sigma-Aldrich) and azidoMultiTASQ (for copper-free click chem, or SPAAC). We developed a protocol for imaging G-quadruplexes (G4s), referred to as in situ click imaging because the TASQ is fluorescently labeled once in its cellular binding site. We also report on a way to isolate G4s by affinity capture, referred to as G4-click-CP (CP for chemoprecipitation) for in vitro investigations, and the well-known G4RP-RT-qPCR for in vivo investigations (described in Nat. Commun. and Nat. Protoc.). This wealth of data is now available in RSC Chem. Biol. (gold open access) and highlighted with the cover! Congrats to the team! 


The GATTACA lab in Strasbourg (FR)

[June 9, 2023The GATTACA lab members (but not only) enjoyed the beautful city of Strasbourg (FR) while attending the 3rd meeting of the GDR ChemBio organized in Illkirch

Happy to see that, together with other students and permanent researchers from Dijon, they also enjoyed some typical beverages from Strasbourg (but not only). 

Poster sessions ahead! 

An article in Cells with our colleagues at the faculty of medicine (Dijon, FR)

[June 6, 2023] Natural polyphenols, such as resveratrol or quercetin, are known to display interesting genoprotective effects. Here, we study another polyphenol, chrysin, found in passionflower and honey, and show that it is quite active against metastatic melanoma, as a result of its ability to both damage cancer cell DNA (which activates the DNA damage response (DDR), both ATM and ATR pathways) and trigger oxidative stress (via reactive oxygen species (ROS) production). Combined, these two effects strongly limit angiogenesis, which was demonstrated here both in vitro and in vivo. Thanks to Dominique Delmas and colleagues (INSERM, Dijon, FR) for associating me in this beautiful study, now published in Cells (gold open access).


Our first iScience article

[May 8, 2023] In the framework of our long-lasting collaboration with the group of Wenli Zhang (Nanjing, PRC)  we compared the G4 capture efficiency of two TASQs, BioTASQ and BioCyTASQ, and the antibody BG4 in a model organism (rice). This unique and direct comparison of chemoprecipitation (TASQs) versus immunoprecipitation (BG4) allowed for both assessing whether these molecular tools can be used interchangeably and defining the limits of their use in sequencing-based technologies (G4DP-seq, using TASQs, BG4-DNA-IP-seq using BG4). This quite long story is now accpeted for publication in iScience (gold open access). Thanks to Wenli and his team!


A novel article in the JACS

[Feb. 17, 2023] While the current literature is replete of examples dealing with the catalytic properties of DNA G-quadruplexes (G4-DNAzyme) when they are associated with hemin, only a handful of them are devoted to the optimization of this catalytic system to reach a terrific catalytic activity. Thanks to the huge work of Jun Zhou’s team, this has been made possible by combining DNA (G4), peptides and hemin in a single, covalent assembly named CPDzyme (for Chimeric peptide-DNAzyme), which outperforms for the very first time the catalytic properties of the corresponding, natural enzyme HRP. These results are now published in the J. Am. Chem. Soc. Thanks Jun, Jean-Louis, for this amazing job! 


A spotlight in Mol. Cell

[Feb. 01, 2023] I would like to sincerely thank Molecular Cell for their invitation to highlight a study published by SG Kennedy, SE Butcher and colleagues published in Nat. Struct. Mol. Biol. regarding a very peculiar G-quadruplex (G4) structure, the pUG fold, which folds from alternating UG RNA sequences. The pUG fold thus escapes from the classical G4-forming motif and thus, keeps on expanding the number of putative genomic G4s (which is already huge!). The spotlight can be found here.


The TASQ story now told in Acc. Chem. Res.

[Jan. 20, 2023] Absolutely delighted to have been invited by Accounts of Chemical Research to tell the story behind the TASQs. Acc. Chem. Res. offers a unique possibility to provide a personalized version of a scientific story and that of the TASQs started back in 2007 in Louisville, KY (USA) during the very 1st international meeting on G-quadruplexes, by an informal discussion with JT Davis. If you are interested in learning more about this >11-year story, have a look to "TASQs: multiTASQing molecular tools for investigating DNA and RNA G-quadruplex biology


Welcome to Shubham (and thank you, EMBO!)

[Dec. 1, 2022] We are happy to welcome Shubham Sharma, from the Indian Institute of Technology, Gandhinagar (IITGN), India. Shubham is currently doing his PhD in the lab of Bhaskar Datta; he successfully obtained an EMBO scientific Exchange grant to spend 5 months in our lab. He will work with Jeremie to apply the G4RP technology to colorectal cancers. Welcome to Dijon!


Two new articles in Nucleic Acids Res. on G-quadruplexes and DNA junctions

[Nov. 17, 2022] We are quite proud that 2 new articles have been accepted for publication in Nucleic Acids Res. concomitantly. In the first one, we explored the roles that G-quadruplexes (G4s) play in stress granules (SG) formation and dynamics. This study is two-fold, combining  an experimental approach aimed at discovering by which cellular processes G4s act on SG formation, and a computational approach in which a machine learning tool  (rG4detector) was developed to predict G4 formation. This work was done in collaboration with Eran Hornstein's lab, at the Weizmann Institute of Science, Rehovot (Israel).  The second one is a review that summarizes the current state of knowledge about DNA junctions (three- and four-way DNA junctions), encompassing their structures and biological relevance along with a description of the cellular consequences of their stabilization by ad hoc ligands for therapeutic purposes. Many thanks to Christine Cardin (at Reading, UK), Kane and Angie for the help! 


Welcome to Sandy

[Oct. 31, 2022] We are delighted to welcome Sandy Raevens for her PhD in the GATTACA lab. Sandy did her M2 internship in the team of Drs. Carine Masquéfa and Cindy Patinote at the IBMM, Montpellier (FR) working on the synthesis of heterocyclic compounds for fighting against pancreatic cancers. She has been selected for the project granted by the CNRS MITI,  in the framework of a collaboration between the CNRS (France) and the Weizmann Institute of Science at Rehovot (Israel). We will thus collaborate with the Eran Hornstein's lab on the roles that G4-RNA plays in stress granules (SGs) formation. Beautiful science ahead!


Two TASQs are now commercially available in the Sigma-Aldrich catalogue

[Oct. 31, 2022] We are really happy and proud that the distribution of two of our TASQs has been licensed by Merck KGaA and are now commercially available in the Sigma-Aldrich catalogue. These two TASQs, the biotinylated BioCyTASQ and the clickable MultiTASQ, can be implemented for various purposes including the affinity purification of both DNA and RNA G4s, their visualization by optical imaging (pre-targeted G4 imaging and in situ click imaging), etc., thus being highly multivalent TASQs or… MultiTASQs  😁 


"Ligue nationale contre le cancer" project granted!

[Oct. 21, 2022] Delighted to be associated to a research program steered by Vincent Geli (CRCM Marseille, FR) on pediatric osteosarcomas now funded by the Ligue National contre le Cancer. This big project, gathering people from Marseille, Toulouse, Dijon, Lille and Strasbourg, aims at uncovering new therapeutic opportunities to treat pediatric cancers. Many thanks to Vincent for gathering such a promising consortium and eager to begin this program very soon!


Dr. Francesco Rota Sperti

[Oct. 20, 2022] Francesco brilliantly defended his Ph.D. work in front of a panel of specialists including Daniela Verga (Institut Curie, Orsay), Filippo Doria (Univ. Pavia, IT),  Fred Boschetti (CEO CheMatech) and Franck Denat (ICMUB's director). We really enjoyed the scientific discussion right after the presentation, which was lively, dynamic, enriching and accurate. We thank once more Francesco for his very hard work with the TASQs (he's responsible for no less than 9 TASQs: CyTASQ and BioCyTASQ, TriazoTASQ and BioTriazoTASQ, MultiTASQ, azidoMultiTASQ and photoMultiTASQ, and the two unpublished tzN-TASQ and SqTASQs)) and wish him all the best for his future endeavors (in Italia).


A review in Trends in Genetics

[July 16, 2022] Wenli Zhang (Nanjing Agricultural University, China) and I provide here a view on what is currently known about genomics applied to the study of alternative DNA structures in plants, including G4s and i-motifs. Plant genetics have been fundamental for genetics (did you ever hear about a Czech monk who discovered the laws of genetics playing with pea plants.. Gregor Mendel? :-)); we aim here at describing how this field has recently and very rapidly evolved, under the impetus of the advances in sequencing techniques. This review is now published in Trends in Genetics.


ANR project granted!

[July 12, 2022] Our collaborative project named InJUNCTION (for Chemical tools for investigating DNA junctions) developed with Anton Granzhan (Institut Curie, Orsay, FR), Sébastien Britton (IPBS Toulouse, FR), Nicolas Chéron (ENS Paris, FR) and Lukas Trantirek (CEITEC Brno, CZ) has been selected by the ANR for granting. We're really happy to have 4 more years (and quite a bit of money :-)) to keep on investigating the biology of three-way DNA junctions in the aim of developing an innovative anticancer strategy. New and promising results soon!


An article in JACS Au 

[June 19, 2022] I am particularly proud about this new article from the group, now published in JACS Au as it reconciles two scientific fields that are very dear to me, G4 and G4-ligand on one side, and DNA damage and genetic instability on the other side. Here, using our new clicked TASQ TriazoTASQ, we keep on developing an innovative G4 imaging technique (pre-targeted G4 imaging) and use it for gaining invaluable insights into the mechanism behind the anti-proliferative activity of G4 ligands (e.g., PDS), providing a quantitative analysis of their DNA damaging properties. Congrats (and thanks) to all co-authors!


CNRS MITI granted!

[June 14, 2022] We thank the CNRS MITI for selecting our project in the framework of a collaboration between the CNRS (France) and the Weizmann Institute of Science at Rehovot (Israel). This grant gives us the unique opportunity to keep on collaborating with the Eran Hornstein's lab on the roles that G4-RNA plays in stress granules (SGs) formation. In the present project we will aim at combining sequencing and proteomics in order to better characterize SG biology. We're happy to work with Yehuda Danino, from the Eran's lab, on this project, as it is a real pleasure to work with such a highly motivated PhD student! More news soon.  


Next talk: G4thering in Marienbad (CZ), June 30, 2022 

[June 12, 2022] Now that the COVID craziness is (almost) over, the G4 community will gather for one week in Marienbad, CZ for the 8th International Meeting on Quadruplex Nucleic Acids (http://g4thering.com/). The program is exciting and it will be so good to see (for real) G4-addict researchers from all over the world to discuss about the latest advances. Many thanks to the organizing committee (Lukas, Silvie and Jean-Louis) for giving me the opportunity to talk about our recent results (on which topic? a hint here :-)). See you there!


Two new articles,  in Anal. Chem. & J. Pharm. Biomed. Anal. 

[May 13, 2022] I would like to thank my long-time collaborator Jun Zhou (Nanjing U., China) and also my new collaborator Carla Cruz (CICS-UBI, Portugal) for giving me the opportunity to be involved in very different projects, from the in-depth study of the catalytic properties of G4s (G4-DNAzyme) on one side to that of the functional relevance and regulatory roles of G4s in miRNA on the other side. The corresponding articles have now been published in Anal. Chem. & J. Pharm. Biomed. Anal., respectively. Many thanks for their trust!


Next talk: CRCM Marseille (FR), May 3, 2022

[Apr. 6, 2022] Happy to be invited by Vincent Geli at the Marseille Cancer Reserach Center (CRCM, France) for discussing about G4-DNA, G4-RNA, genomic instability and.. fishing (yes, so close to the Mediterranean sea, an all too easy and cheap joke ;-))


An article in Nature Protocols!

[Apr. 4, 2022] All details you need to efficiently fish G-quadruplex-RNA (G4-RNA) from human cells using  the G4RP-seq method (for G4-RNA precipitation & sequencing), initially described in Nat. Commun. are now thoroughly described in our Nat. Protoc. article. Many many thanks to Sunny Y. Yang and Judy M. Y. Wong (UBC Vancouver, CA) for their dedication and commitment to this protocol, to make it ever more simple and reliable!


Our Plant Phys. and Nucleic Acids Res. articles highlighted

[Apr. 1, 2022] The two articles we have the chance to publish with Wenli Zhang, from Nanjing Agricultural University, PRC, on the genome-wide  discovery of both G4s (Plant Phys. article) and i-motifs (Nucleic. Acids Res. article) and their regulatory roles in plants (rice) have been highlighted in Plant Phys. by Maryam Foroozani (Emory Univ. Atlanta, USA) and in Trends in Plant Science by Martin Crespi (Paris Saclay, FR) & Frederico Ariel (Univ. Santa Fe, ARG). Our technology for tracking G4s in plants named BG4-IP-seq was also selected as the "Technology of the Month" by Trends in Plant Science. Many thanks for you kind words! 


An article in Nucleic Acids Res., on i-motifs (for once!)

[Feb. 8, 2022] I would like to sincerely thank again Wenli Zhang, from Nanjing Agricultural University, China for his large-scale study of the roles that i-motifs (iMs, some sort of C-quadruplexes) play in the regulation of the gene expression in plants (rice). To this end, and in a manner that is fully reminiscent of what was done for G4s (see below) he has developed a genome-wide mapping referred to as iM-IP-seq that provides an unbiased demonstration of  the regulatory roles of iMs in plant genetics. Honored and happy to be associated to this study now published in Nucleic Acids Res.