A new regulatory mechanism involved in the bacterial response to cold shock

Cold shock is a common stress for bacterial pathogens inhabiting warm-blooded hosts. It occurs upon abrupt release from the host into the comparatively cold environment. Understanding how pathogens cope with cold shock is crucial to define how they survive on contaminated surfaces and spread to new hosts.

The‘RNA remodeling’ team and I2BC colleagues discovered that transcription termination factor Rho is a crucial player in the bacterial cold shock response (CSR), challenging the prevalent view that the CSR is mostly a posttranscriptional program. Temperature-sensing mRNA switches either allow (at 37°C) or prevent (at 15°C) Rho-dependent termination of the transcription of cold shock genes. During cold acclimation, the cold shock proteins accumulate until they bind to their mRNAs and switch them back into conformations prone to Rho action, thereby providing negative feedback control of their own expression. This regulatory loop works alongside the established posttanscriptional mechanisms to ensure tight and quick regulation of the cold shock genes.

This discovery published in the journal Molecular Cell illustrates the complexity of the bacterial stress responses and highlights Rho as a promising therapeutic target. It was reported by CNRS Chimie on its website.

Référence :
Rho-dependent transcriptional switches regulate the bacterial response to cold shock
Mildred Delaleau, Nara Figueroa-Bossi, Thuy Duong Do, Patricia Kerboriou, Eric Eveno, Lionello Bossi, & Marc Boudvillain*
Molecular Cell https://doi.org/10.1016/jmolcel.2024.07.034

Contrast agents to combine 1H and 19F MRI

Today, magnetic resonance imaging (MRI) is based on the detection of water protons (1H) in tissues. MRI of 19F fluorine offers complementary advantages, but its use is hampered by a lack of suitable imaging agents, soluble in water and easily detectable. In order to improve the sensitivity of detecting 19F MRI signals, a CBM team used Mn2+ ions to form complexes with small fluorinated molecules. Unlike currently used nanoparticles, these small molecular probes have well-defined chemical structures and better biocompatibility and water solubility. Finally, thanks to the paramagnetism of manganese(II), they generate a strong signal in MRI. In addition, these fluorinated contrast agents are also active in proton MRI, allowing proton and fluorine MRI images to be superimposed for precise anatomical mapping.

This advance, published in Angewandte Chemie International Edition, opens new horizons in fluorine MRI. It was reported by CNRS Chimie on its website.

Reference :
Small, Fluorinated Mn2+ Chelate as an Efficient 1H and 19F MRI Probe
Éva Tóth, Zoltán Garda, Frédéric Szeremeta, Océane Quin, Enikő Molnár, Balázs Váradi, Rudy Clémençon, Sandra Même, Chantal Pichon and Gyula Tircsó
Angewandte Chemie International Edition, 2024
DOI: 10.1002/anie.202410998

Software is ubiquitous in science, yet overlooked

A recent article in the journal Nature Computational Science, co-authored by fourteen international authors, summarizes the many facets of software in scientific research.

At a time when the scientific world (and beyond) is talking about code, algorithms, and even artificial intelligence, talking about "software" seems to be just another semantic subtlety. Yet there are many facets of software, such as issues of licensing and file formats, that are not part of the definition of code or algorithms. The authors, humanities scholars and practitioners of scientific computing, draw attention to these facets of software that are neglected by researchers, research organizations and funding agencies alike: engineering, governance, licensing, circulation, infrastructure, embedded theory, and users.

Computational chemistry plays an important role in this analysis, because it was one of the first disciplines in which the tension between the industrial and academic approaches to quality assurance became evident. For some, software is reliable if it has been professionally developed according to the best practices of software engineering, while for others, it is the transparency and malleability of Open Source code that guarantees reliability.

See the article:
Hocquet, A., Wieber, F., Gramelsberger, G. et al. Software in science is ubiquitous yet overlooked. Nat Comput Sci (2024). https://doi-org.insb.bib.cnrs.fr/10.1038/s43588-024-00651-2

Protein filaments in the regulation of gene expression

Although every cell in our body contains the same genetic information, cells differ in the way they use it, a process known as “gene expression”. The regulation of gene expression is orchestrated by proteins called transcription factors, which bind to specific sequences within DNA. Transcription factors are traditionally thought to operate mainly as single molecules or dimers.

The article by Mance et al. reveals that several transcription factors of the family known as ZBTB, present in humans and other animals, have the capacity to form non-covalent filamentous structures composed of numerous identical copies of proteins arranged in a chain. At the molecular level, such structures could offer significant advantages for binding to DNA, which is itself an elongated molecule containing numerous repeated sequences. A few examples of filament-forming transcription factors had already been reported, but this study extends the concept to a large family of this protein with important functions. The study - which combines structural, biophysical and functional analysis carried out in vitro and in cells - was carried out by the "Post-translational modifications and DNA repair" team at the CBM and their collaborators in Orléans, Rennes and Marseille, including the "Functional mass spectrometry of molecular assemblies" team also at the CBM.

The findings from this research, together with a complementary study by groups of Benjamin Ebert and Eric Fischer from Dana-Farber Cancer Institute at Harvard (published back-to-back in the same issue of Molecular Cell), challenge the traditional view of transcription factor functionality.

In cells, ZBTB proteins are regulated through a process called SUMOylation, where a small tag called SUMO is added to them, changing how they function. Studies on ZBTB proteins undertaken in Orléans, during which the filamentous structures were discovered, are part of the "SUMOwriteNread" project funded by the European Union (ERC grant no 101078837). Researchers are currently investigating the interplay between the ability to form filaments and SUMO tagging to understand the complex reality of gene expression regulation.

This research was reported by CNRS Chimie on its website.

Dynamic BTB-domain filaments promote clustering of ZBTB proteins.
Lucija Mance, Nicolas Bigot, Edison Zhamungui Sánchez, Franck Coste, Natalia Martín-González, Siham Zentout, Marin Biliškov, Zofia Pukało, Aanchal Mishra, Catherine Chapuis, Ana-Andreea Arteni, Axelle Lateur, Stéphane Goffinont, Virginie Gaudon, Ibtissam Talhaoui, Ignacio Casuso, Martine Beaufour, Norbert Garnier, Franck Artzner, Martine Cadene, Sébastien Huet, Bertrand Castaing & Marcin Józef  Suskiewicz
Molecular Cell 2024
https://doi.org/10.1016/j.molcel.2024.05.029

Dual agents for non-invasive imaging of living organisms

Researchers in the "Lanthanide Luminescent Compounds, Spectroscopy and Optical Bioimaging" team have designed a molecular probe that can image living organisms using both near-infrared (NIR) luminescence and photoacoustic (PA) signal detection. These two complementary imaging techniques make it possible to monitor biological events precisely, in real time and non-invasively.

Find out more

A Dual-Mode Near-Infrared Optical and Photoacoustic Imaging Agent Based on a Low Energy Absorbing Ytterbium Complex
Anton Kovalenko, Svetlana V. Eliseeva, Guillaume Collet, Saïda El Abdellaoui, Sharuja Natkunarajah, Stéphanie Lerondel, Laure Guénée, Céline Besnard & Stéphane Petoud
JACS 2024
https://doi.org/10.1021/jacs.4c03406

Breast cancer: towards early diagnosis by imaging

In vivo imaging of metastatic breast cancer tumors at very early stages is about to become possible. A team of chemists and biologists from the Center for Molecular Biophysics (CNRS) has indeed developed a new magnetic resonance imaging (MRI) probe which has a selective affinity for an emerging biomarker of metastatic breast cancer: Netrin- 1. Find out more on the Cnrs Chimie website.

See more and Cnrs Chmie website.

Reference
Peptide-Conjugated MRI Probe Targeted to Netrin-1, a Novel Metastatic Breast Cancer Biomarker
Clémentine Moreau, Tea Lukačević, Agnès Pallier, Julien Sobilo, Samia Aci-Sèche, Norbert Garnier, Sandra Même, Éva Tóth & Sara Lacerda
Bioconjugate Chemistry 2024
https://doi.org/10.1021/acs.bioconjchem.3c00558

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