Typologie d'actualités: CBM
2024, March 29 – Seminar of Yu Kimura

Watching enzymes work in vivo with rare-earth-based molecular probes

Scientists at the CNRS Centre de Biophysique Moléculaire (CBM) in Orléans and the Institut de Chimie des Substances Naturelles (CNRS/Université Paris-Saclay) have designed luminescent probes. They are based on complexes of lanthanides (Ln), a series of rare-earth metals whose trivalent Ln3+ ions are luminescent. The special feature of these probes is that the activity of certain enzymes can modify their luminescence in the near infrared, as well as the signal observed on MRI. These probes make it possible to track the catalytic activity of an enzyme with a single molecule using several complementary imaging techniques: MRI and near-infrared optics. Essential for unambiguous detection of a biological phenomenon, this dual imaging with a single molecule avoids biases due to the use of chemically different imaging agents for each imaging technique.
This study, published in the journal Angewandte Chemie International Edition, paves the way for new non-invasive diagnostic strategies.
This work has been reported on the Cnrs Chimie website
Article reference
Lanthanide-Based Probes for Imaging Detection of Enzyme Activities by NIR Luminescence, T1- and ParaCEST MRI
Rémy Jouclas, Sophie Laine, Svetlana V. Eliseeva, Jérémie Mandel, Frédéric Szeremeta, Pascal Retailleau, Jiefang He, Jean-Francois Gallard, Agnès Pallier, Célia S. Bonnet, Stéphane Petoud, Philippe Durand & Éva Tóth
Angew. Chem. Int. Ed. 2024
https://onlinelibrary.wiley.com/doi/10.1002/anie.202317728

Details of the 4 thesis offers:
Thesis subject: "Suffering at work and consumption of psychoactive substances among territorial agents of the Communauté de commune des Terres du Val de Loire (TraPsyCOL)"
Supervisor: Raphaël Serreau, Neurobiology of receptors and therapeutic innovations team
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Thesis subject: "Molecular assembly of synthetic microRNAs in intracellular condensates of human glioblastoma cells"
Supervisors: Patrick Baril and Séverine Morisset-Lopez, Neurobiology of receptors and therapeutic innovations team
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Thesis subject: "Discovery and total chemical synthesis of D-proteins for molecular targeting of tumor glyco-epitopes"
Supervisors: Vincent Aucagne and Carlo Pifferi, Synthetic proteins and bioorthogonal chemistry team
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Thesis subject: "Anti-hOGG1 nanobodies to study the interactions between DNA repair and transcription regulation and to modulate the action of hOGG1 in anti-cancer strategies"
Supervisor: Bertrand Castaing, “Post-translational modifications of proteins and DNA repair: structure, functions and dynamism” team
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2024, March 22 – Seminar of Marie Catherine Sforna

The study of terrestrial fossils in ancient rocks: a crucial approach to identify potential signs of life on Mars

The NASA Perseverance rover is actively exploring Jezero Crater, analyzing igneous and sedimentary rocks from the crater floor and delta deposits. The rock samples that will be returned by the Mars Sample Return (MSR) mission in the 2030s will be subjected to detailed laboratory studies.
Some samples may contain traces of ancient Martian life, which are challenging to detect due to their morphological simplicity and subtle geochemical expressions. Using volcanic sediments from Kitty’s Gap Chert (Pilbara, Australia) of 3.45 billion years as analogues, researchers detail the steps needed to demonstrate their syngenicity and biogenicity. Various analytical methods, including optical and electron microscopy, Raman spectroscopy, X-ray fluorescence spectroscopy, and mass spectrometry, have been employed at different scales. Sedimentological, petrological, mineralogical, and geochemical analyses document a coastal environment of deposition, consistent with the development of microbial life. Morphological, elemental, and molecular analyses of carbonaceous matter associated with potential fossil remnants reveal enrichment in bioessential trace metals (V, Cr, Fe, Co, etc.) and colocalized aromatic and aliphatic molecules of biological origin. This study illustrates the analytical protocol necessary to optimize the detection of fossil traces of life in Martian rocks.
This work is reported on the CNRS Chimie website
Reference
Multi-Technique Characterization of 3.45 Ga Microfossils on Earth: A Key Approach to Detect Possible Traces of Life in Returned Samples from Mars
Laura Clodoré, Frédéric Foucher, Keyron Hickman-Lewis, Stéphanie Sorieul, Jean Jouve, Matthieu Réfrégiers, Guillaume Collet, Stéphane Petoud, Bernard Gratuze, Frances Westall
Astrobiology 2024
http://doi.org/10.1089/ast.2023.0089
Enzymatic detection in near infrared optical imaging and MRI with a single ligand complexed to different lanthanide ions

The imaging visualization of active enzymes is of primary importance in biology.
In a collaborative effort between the Centre of Molecular Biophysics (CBM) and the Institute of Chemistry of Natural Substances (ICSN) in Gif sur Yvette, CBM researchers have designed Ln3+ complexes that provide enzyme-mediated changes in NIR luminescence, as well as in Chemical Exchange Saturation Transfer (CEST) and classical T1-weighted MRI, depending on the Ln3+ used. They have demonstrated the successful monitoring of b-galactosidase activity over time in NIR luminescence and CEST MR imaging in phantoms containing the Yb-complex, and in T1 MRI when using the Gd-analogue. A further great advantage of their probe design is its high versatility, as there are a large number of enzymatically cleavable groups that could be attached to the same core, thus creating probes for other important enzyme targets.
Reference : Rémy Jouclas, Sophie Laine, Svetlana V. Eliseeva, Jérémie Mandel, Frédéric Szeremeta, Pascal Retailleau, Jiefang He, Jean-Francois Gallard, Agnès Pallier, Célia S. Bonnet, Stéphane Petoud, Philippe Durand, Éva Tóth
Lanthanide-Based Probes for Imaging Detection of Enzyme Activities by NIR Luminescence, T1- and ParaCEST MRI
Angew. Chem. Int. Ed. 2024, https://onlinelibrary.wiley.com/doi/10.1002/anie.202317728