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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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

Comprehensive review about the “logic of protein modifications”

Among the main functional building blocks of living cells are proteins, small “molecular machines” produced by the cell according to the information encoded in genes. Each protein has its characteristic chemical composition which defines its structure and function.

In some circumstances, the chemical composition of a protein can be changed in an enzymatic process known as post-translational modification (PTM), whereby additional chemical groups are covalently attached to the protein. PTMs are used by the cell as a regulatory mechanism to control protein function. The addition of new chemical groups – which can come in different shapes and sizes, ranging from small groups, through sugars and lipids, to small proteins – changes the structure and interactions of a protein and can impact almost any aspect of its function.

Marcin Suskiewicz, a structural biologist and biochemist from the CBM, has devoted many years to studying various types of protein PTMs and currently supervises a project devoted to one particular type of PTMs, protein SUMOylation.

In the review published in the journal BioEssays, he reviews the history of the research into protein PTMs as well as various facets of this phenomenon, including the underlying chemical principles, molecular mechanisms, and evolution.

The review combines an introduction to the field with an overview of the recent literature and new ideas and hypotheses.

References:

The logic of protein post-translational modifications (PTMs): Chemistry, mechanisms and evolution of protein regulation through covalent attachments
Marcin Suskiewicz
BioEssays
First published:21 January 2024
https://doi-org.insb.bib.cnrs.fr/10.1002/bies.202300178