2021
An article in Plant Physiology
[Dec. 15, 2021] Francesco and I would like to sincerely thank Wenli Zhang, from Nanjing Agricultural University, China for associating us to his large-scale study of the roles that G-quadruplexes (G4s) play in the regulation of the gene expression in plants (rice). To this end, he has developed a genome-wide mapping referred to as BG4-IP-seq that provides an unbiased demonstration of the regulatory roles of G4 and the intimate relationship between G4 genetics and epigenetics. Happy to be associated to this study now published in one of the oldest and most well-respected journals in the field of plant biology, Plant Physiology.
Next talk: INTERACTION WINS (on-line)
[Nov. 22, 2021] Happy to be involved in INTERACTION WINS (Innovative ThERApeutiC Targets In nOn- canonical Nucleic acids structures Winter InterNational School 2021) an on-line event devoted to non-canonical DNA and RNA structures organized by Valentina Pirota (University of Pavia, IT) and colleagues. All details (and program) can be found here: http://interactionwins.com/
Welcome to Jiri
[Oct. 1, 2021] We are more than happy to welcome Jiri Ledvinka in the GATTACA lab for his M2 internship. Jiri's work is undertaken in the framework of a collaboration between our lab and the Petra Menova's lab in Prague, CZ. Jiri will work on the rather complicated chemistry (and biophysical properties) of the twice-as-smart G4 ligand N-TASQ and its derivatives. We hope that he will enjoy his stay in Dijon!
A new article in Nucleic Acids Res. on dual TWJ-/G4-ligands
[Sep. 23, 2021] Super proud of this team work combining the expertise of Sébastien (biology, IPBS Toulouse), Anton (chemistry, Institut Curie, Orsay), Nicolas (theoretical chemistry, ENS Paris) and their students. Altogether, we designed and study a series of azacryptands that interact with both G-quadruplexes (G4s) and three-way DNA junctions (TWJs) in vitro, but whose cellular properties are mostly governed by their interactions with TWJs. We notably studied their ability to trigger DNA damage, exploit this to define valuable chemically induced synthetic lethality strategy and decipher (part of) their mechanism of action. A thrilling chemical biology project, which also provides the first bona fide demonstration of the existence of TWJs in human cells, now fully described in Nucleic Acids Res. Congrats again to all coauthors!
Welcome to Angie
[Sep. 1, 2021] We are more than happy to welcome Angélique (Angie) Pipier for her post-doc stay in our lab. She will work on the three-way DNA junction (TWJ) biology, as a continuation of the Jo's work. And she has all the required skills to do that! She was indeed trained in our friend Seb Britton's lab (IPBS Toulouse), during her PhD under the supervision of Dennis Gomez. We are really really happy to welcome her in the GATTACA lab!
Our JACS article in the news
[Aug. 30, 2021] Our recent article in the JACS about the first prototype of G4-unfolder has been highlighted both by the CNRS and by our university (in French). Congrats again to all coauthors!
An article in JACS about G-quadruplex unwinding
[July 23, 2021] Our long quest for small-molecules able to unfold G-quadruplexes (G4s) has finally paid off! We are really proud to report on the first, fully validated prototype of G4-unfolder that has been identified through a series of in vitro tests, including the new G4-unfold assay and a novel version of a qPCR stop assay. This workflow has permitted the identification of PhpC, which displays highly promising G4-disrupting properties. These results have now been accepted for publication in the JACS. Congrats to all coauthors!
An article in NAR Cancer on ALT cancers, G4s and R-loops
[July 1st, 2021] Our friend Judy Wong (UBC Vancouver, Canada) is a specialist of both telomeres and G-quadruplexes (G4s). She recently invested massive efforts in deciphering the very complicated relationship between telomeres and alternative DNA structures in the context of alternative-lengthening-of-telomere (ALT) mechanism, which is a recombination-based maintenance method used by 10 to 15% of human cancers. She discovered that G4s are spatially related to DNA/RNA hybrids known as R-loops and that they together contribute to enhance ALT-activity. We are happy that the molecular tools we developed recently were useful for achieving this, and honored to be associated to this beautiful study now accepted for publication in NAR Cancer. Congrats to all coauthors and many thanks to Judy!
An article in Aging on G-quadruplexes in different brain cells
[Jun. 17, 2021] Thanks to our ongoing collaboration with Andrey Tsvetkov (UThealth, TX, USA) we keep on investigating the roles the G-quadruplexes (G4s) may play in the central nervous system (CNS). We found that G4 landscapes differ from microglia (which mediate immune responses in the brain), astrocytes (which are supportive glial cell components in neural tissue) and neurons (which send and receive signals from the brain). Stabilizing G4s with ad hoc ligands creates DNA damage that are repaired in cell type-dependent manner. Collectively these results now published in Aging keep on demonstrating that G4s contribute to genetic instability in CNS cells. Congrats to all coauthors!
A new article in ACS Chem. Biol. on new TASQ-based molecular tools
[Apr. 29, 2021] We keep on expanding our portfolio of TASQs molecular tools to interrogate G4 biology. Two new TASQs are now ready to help us in this endeavor, CyTASQ and BioCyTASQ, which have been synthesized by Francesco. Happy that this new generation TASQ, far more readily chemically accessible than the previous biotinylated TASQ (BioTASQ v.1 and v.2, cf Nucleic Acids Res. 2019) share the exquisite properties of the parent compounds, making them new players in the field of G4 visualization and identification. These results are now published in ACS Chem. Biol. Congrats to all coauthors!
Welcome to Marta and Baptiste
[Feb. 2, 2021] We are really happy to welcome two Master 2 students in the lab for the next 5 months (hopefully.. I mean, depending on whether there is a new lock-down or not..). Marta Hernandez Garcia will work with Jo on the targeting of three-way DNA junctions for therapeutic purposes; Baptiste Dupouy will work with Francesco on the synthesis of multitasking TASQ. Welcome to the lab and.. enjoy the (scientific) journey!
A beautiful way to start the new year..
[Jan. 15, 2021] We started the new year with a rather provocative question in mind: in light of the most recent results regarding G4 biology, should we continue to search for G4-stabilizing ligands or would it not be wise to invest efforts in designing and exploiting molecular tools able to unfold G4s? In line with our recent bioRxiv article describing G4-disrupting molecules, we decided to have a closer look at the recent efforts invested to design and use of molecular tools able to unfold G4s, being either proteins known as G4-helicases or small-molecules. This cast a bright light on what could be the therapeutic consequences of manipulating G4 in cells to treat genetic diseases. These results are now gathered and summarized in a review that is now accepted for publication in Cell Chemical Biology.