[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!
[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.
[Sep. 11, 2023] After 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!
[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!
[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
[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 ;-)
[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.
[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).
[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!
[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. :-)
[July 4, 2023] After 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!
[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!
[June 9, 2023] The 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!
[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).
[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!
[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!
[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.
[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"