I2BC Paris-Saclay

A novel structural device used by bacterial retrotransposons to efficiently invade host genomes was identified. These results will also contribute to the rational design of new RNA-based gene targeting systems for bacterial genome engineering.

Mobile group II introns are site-specific retrotransposable elements widespread in bacterial genomes and in organelles (mitochondria and chloroplasts) of plants, algae and fungi. They constitute the most abundant class of retrotransposons in bacteria and play a major role in the diversification and evolution of bacterial genomes. Mobile group II introns are composed of a large and highly structured self-splicing intron and an intron-encoded reverse transcriptase. They colonize genomes by 'Retrohoming', a very efficient and specific pathway that is operated by the combined activities of the self-splicing intron and its reverse transcriptase. During the first stage of mobility, the intron RNA catalyzes its own insertion directly into the DNA target site. Recognition of the proper target rests primarily on multiple base pairing interactions between the intron segments ‘EBS’ and complementary 'IBS' sequences present on the double-stranded DNA target (Figure 1A). Remarkably, the sequence of the EBS sites can be modified, thus allowing to 'reprogram' a group II intron to specifically integrate into a desired DNA target. This feature is at the basis of the powerful 'Targetron' technology, now commonly used for bacterial genome engineering. Using bioinformatics and genetic approaches, Maria Costa and collaborators have identified a novel base pairing interaction between the intron RNA and the DNA target that is essential for intron mobility. This pairing, named 'EBS2a-IBS2a', adopts a Watson–Crick geometry and helps inducing a structural conformation that favors the opening of the DNA double helix and the integration of the retrotransposon into the genome (Figure 1B). The authors also showed that the EBS2a-IBS2a interaction is perfectly 'reprogrammable'. This work has direct biotechnological applications by allowing the development of new 'targetrons' capable of inserting themselves into genomic sites that were previously inaccessible to disruption by these systems.

More information here.

Contact person: Maria Costa

I2BC teams collaborate and create a teaching project to discover new phages with Bachelor students from Université Paris-Saclay.

Financed by a grant from the University Paris-Saclay to develop teaching innovation, lecturers from I2BC’s Virology and Microbiology Departments have created a new lab course unit, called “Phage Discovery”, for second-year Bachelor students.
In September 2021, thirteen “phage hunters” signed up for this elective course and collected soil and water samples from the campus of Orsay and surroundings. Following purification, they isolated three distinct viruses that infect the bacterium Corynebacterium glutamicum. The students were welcomed by the cryo-electron microscopy platform of I2BC by Ana Arteni, Laura Pieri and Malika Ould Ali. Student phage hunters were dazzled by electron micrographs of their phage samples. Their day at the platform was the highlight of their first research experience.
The project will continue after the sequencing of the viral DNA by the I2BC platform: third-year Bachelor students will annotate the phage genomes. Stay tuned!
Contact: Ombeline Rossier, Christophe Regeard 

EMBO in-person workshop on Protein Termini in Bergen Norway 8-11 June 2022
Here is the complete list of 32 confirmed speakers: 15-20 additional speakers will be selected from the abstracts.
Don't miss this chance to join world-leading PI in the beautiful city of Bergen.
Deadline 11 March 2022!

 https://meetings.embo.org/event/21-protein-termini

The atomic structure of the nanotubes of Lanreotide, a therapeutic peptide, reveals a complexity that nothing allowed to suspect until now.

Peptide assemblies forming hydrogels or fibrils are used for biomedical applications such as drug and vaccine formulation, cell culture and tissue regeneration. To enable the rational design of these self-assembled peptides, a thorough understanding of the chemical and physico-chemical rules guiding the folding and assembly of these molecules is required. With recent developments in cryo-electron microscopy (cryo-EM), the determination of these structures at the atomic scale has become possible. The study presented makes it possible to reveal by cryo-EM the atomic structure of nanotubes of a therapeutic peptide, Lanreotide. This structure is of a complexity that nothing allowed to suspect until now. These results are published in the journal PNAS.

Functional and versatile nano- and micro-assemblies formed by biological molecules are found at all levels of life, from cellular organelles to complete organisms. Understanding the chemical and physico-chemical determinants guiding the formation of these assemblies is crucial not only to understand the biological processes that they implement but also to mimic nature through the rational design of self-assembled objects that can be used in particular biomedical level. These assemblies result from deterministic chemical interactions and are therefore all potentially predictable. But currently we simply lack the tools to predict how peptides assemble and the potentially polymorphic architectures they can form. To acquire predictive tools based on learning, we need to identify and understand a large number of peptide assembly structures.

Among synthetic peptides forming well-defined nanostructures, the octapeptide Lanreotide has been considered one of the best characterized, both in terms of structure and self-assembly process. Lanreotide is a therapeutic peptide used against acromegaly and certain neuroendocrine cancers. This peptide self-assembles spontaneously in water in the form of nanotubes 24 nm in diameter and extremely long (around one mm), explaining the formation of a hydrogel. This hydrogel allows Lanreotide not only to be protected against chemical degradation but also to be released in a controlled manner over time (more than a month after injection) ensuring its continuous circulation in the blood. The detailed understanding of the chemical and physicochemical rules guiding the assembly of peptides would make it possible to design new controlled-release formulations in which, as in the case of Lanreotide, the drug would be its own formulation. Scientists elucidated the atomic structure of Lanreotide nanotubes obtained at a resolution of 2.5 Å by cryo-EM. This structure reveals a complexity that nothing let suspect in the many previous works and that it would have been impossible to predict by the methods we have today.

The recent and phenomenal success of the artificial intelligence software AlphaFold for the prediction of the tertiary structure of proteins has only been possible thanks to the database of experimentally determined protein atomic structures. However, AlphaFold is not at this stage able to predict peptide folding and assembly. The experimental verification of models at a level of resolution close to the atom must therefore become the norm in this field. This will be an essential step towards the development of reliable predictive methods which will pave the way for the de novo design of peptide materials whose controlled properties will thus find applications in many fields of biology, pharmacy and medicine and may inspire developments in the field of nanotechnology.

I2BC news

Contact person: Maïté Paternostre

Team Interactions and assembly mechanisms of proteins and peptides

Cell cycle regulating GANTC methylation patterns in the Sinorhizobium meliloti genome are remodelled during differentiation of this endosymbiont within plant cells, suggesting an epigenetic regulation of a bacterial differentiation process.

In the rhizobium-legume symbiosis, the symbiotic bacteria are housed inside specific plant cells of root nodules where they fix nitrogen. These endosymbiotic rhizobia, called bacteroids, are metabolically differentiated and adapted to intracellular life. In legumes belonging to the genus Medicago, bacteroid differentiation of the symbiont Sinorhizobium meliloti involves also irreversible cellular modifications, including cell enlargement and genome amplification. By genome-wide DNA methylation analysis with SMRT-seq during the different stages of bacteroid differentiation in wild type plants as well as in a panel of plant mutants whose nodules contain endosymbionts blocked at various stages of differentiation, we obtained in this study evidence of dysregulated GANTC methylation patterns during bacteroid differentiation. We therefore propose that epigenetic control by the DNA methylase CcrM is a driving factor for the endoreduplication of the differentiated bacteroids.

More information: https://doi.org/10.1128/mSystems.01092-21

Contact person: Peter Mergaert 

Team Plant-Bacteria Interactions

In this review in Current Opinion in Microbiology special issue, we discuss recent insights into the role of RNAs in modulating interactions between the emerging human enteropathogen C. difficile and phages in light of intriguing data in other prokaryotes.

Clostridioides difficile (formerly Clostridium difficile)-associated diarrhea is currently the most frequently occurring nosocomial diarrhea worldwide. During its infection cycle this pathogen needs to survive in phage-rich gut communities. Recent data strongly suggest that regulatory RNAs control gene expression in C. difficile and many of these RNAs appear to modulate C. difficile-phage interactions. Of the 200 regulatory RNAs identified by deep sequencing and targeted approaches, many function as antitoxins within type I toxin-antitoxin (TA) modules and CRISPR RNAs for anti-phage defenses. The purpose of this review is to give an overview of the RNAs contributing to the interactions of C. difficile with phages focusing on CRISPR-Cas and TA systems in light of intriguing recent data in other prokaryotes. We first describe what is known about the contribution of phages to C. difficile physiology and then highlight the recent findings on the emerging roles of RNAs in C. difficile-phage interactions. Open questions that arise from these first observations and future directions with potential roles of additional classes of regulatory RNAs are discussed. This increasing knowledge provides essential basis for future development of new molecular tools as well as promising diagnostic and therapeutic applications.

More information: https://doi.org/10.1016/j.mib.2021.11.012

Contact person: Olga Soutourina

FRAP experiments with mEOS provide evidence of the essential role of the protein pKu70 in DNA repair.

Canonical non-homologous end-joining (cNHEJ) is the prominent mammalian DNA double-strand breaks (DSBs) repair pathway operative throughout the cell cycle. Phosphorylation of Ku70 at ser27-ser33 (pKu70) is induced by DNA DSBs and has been shown to regulate cNHEJ activity, but the underlying mechanism remained unknown. Here, we established that following DNA damage induction, Ku70 moves from nucleoli to the sites of damage, and once linked to DNA, it is phosphorylated. Notably, the novel emanating functions of pKu70 are evidenced through the recruitment of RNA Pol II and concomitant formation of phospho-53BP1 foci. Phosphorylation is also a prerequisite for the dynamic release of Ku70 from the repair complex through neddylation-dependent ubiquitylation. Although the non-phosphorylable ala-Ku70 form does not compromise the formation of the NHEJ core complex per se, cells expressing this form displayed constitutive and stress-inducible chromosomal instability. Consistently, upon targeted induction of DSBs by the I-SceI meganuclease into an intrachromosomal reporter substrate, cells expressing pKu70, rather than ala-Ku70, are protected against the joining of distal DNA ends. Collectively, our results underpin the essential role of pKu70 in the orchestration of DNA repair execution in living cells and substantiated the way it paves the maintenance of genome stability.

More information here.

Contect person: Romain Le Bars

We show that DNA supercoiling can be flipped from positive to negative in the archeon Thermococcus kodakarensis without adverse effect for its growth. This archaeon seems to be remarkably resistant to such topological stress, in stark contrast to bacteria in which DNA supercoiling is tightly regulated by topoisomerases.

In all cells, DNA topoisomerases dynamically regulate DNA supercoiling allowing essential DNA processes such as transcription and replication to occur. How this complex system emerged in the course of evolution is poorly understood. Intriguingly, a single horizontal gene transfer event led to the successful establishment of bacterial gyrase in Archaea, but its emergent function remains a mystery. To better understand the challenges associated with the establishment of pervasive negative supercoiling activity, we expressed the gyrase of the bacterium Thermotoga maritima in a naïve archaeon Thermococcus kodakarensis which naturally has positively supercoiled DNA. We found that the gyrase was catalytically active in T. kodakarensis leading to strong negative supercoiling of plasmid DNA which was stably maintained over at least eighty generations. An increased sensitivity of gyrase-expressing T. kodakarensis to ciprofloxacin suggested that gyrase also modulated chromosomal topology. Accordingly, global transcriptome analyses revealed large scale gene expression deregulation and identified a subset of genes responding to the negative supercoiling activity of gyrase. Surprisingly, the artificially introduced dominant negative supercoiling activity did not have a measurable effect on T. kodakarensis growth rate. Our data suggest that gyrase can become established in Thermococcales archaea without critically interfering with DNA transaction processes.

More information here.

Contact person: Tamara Basta

Chloé Quignot was awarded "Prix 2021 du Groupe Graphisme et Modélisation Moléculaire (GGMM)" for her PhD thesis in the group "Molecular Assemblies and Genome Integrity".

Chloé Quignot received the GGMM prize for her thesis entitled "Modelling Protein interfaces using evolutionary information", carried out at the I2BC, B3S department, in the Molecular Assemblies and Genome Integrity team and co-supervised by Jessica Andreani and Raphael Guerois. Chloé presented her thesis work at the GGMM-SFCi conference held in Lille in October 2021.
The Graphical and Molecular Modeling Group (GGMM) is a learned society that brings together a large part of the French community whose activity is dedicated to, or involves, the use of molecular modeling. The GGMM prize is awarded every two years for original work in molecular modeling, bioinformatics, chemoinformatics and numerical simulation in the field of structural biology and pharmacology.

Congratulations, Chloé!

more information here.

We are very pleased to announce that Magali Noiray arrived this summer to work on the PIM platform.This arrival coincides with the commissioning of BLI, a new machine dedicated to the study of macromolecular interactions.

Magali Noiray has a solid expertise in the field of the study of macromolecular interactions (SPR, ITC, DSC...) and worked for 10 years on the interaction platform of Chatenay Malabry (Pharmacy Faculty) specialized in nanomedicines and small molecules. She joined the PIM platform this summer to strengthen the team and to work with Magali Aumont. In parallel, thanks to funding obtained last year from the Ile de France region , we have obtained and put into operation a new device to replace the SPR. Based on Bio-Layer Interferometry (BLI), the fluidics-free ForteBio’s Octet® RED96 system is a multi-functional, label-free, real-time analysis instrument. It is ideal for rapidly screening protein-protein, protein-nucleic acids and protein-small molecule interactions. The Octet RED96 system can be used for a wide range of analyses. System provides up to 8-channel quantitation and kinetic measurements of molecules greater than 150 Da, compatibility with 96-well plates and cooling for temperature control down to 15°C.

Team Protein Interaction

Mass spectrometry was used to investigate the role of PpKAI2L protein in the moss Physicomitrium patens as receptor of a class of phytohormones , striptolactones, in the moss Physcomitrium patens and to compare this processes with the more known vascular plants. Results on Physcomitrium highlight surprising evolutive innovations from vascular plant.

Abstract from The Plant Clell article: Strigolactones (SL) make up a novel class of phytohormones that are found across the whole land plant lineage. In vascular plants, the main hormonal role of SL is the repression of shoot axillary branching. However, SL are also a major symbiotic signal, granting the plant increased access to the nutrients and water contained in the rhizosphere. These two functions of SL led to the hypothesis that these molecules have been instrumental at the time of land colonization by plants, approximately 450 million years ago. Studying SL biosynthesis and signaling in the bryophyte Physcomitrium patens (P. patens, a non-vascular plant), and comparing these processes with the available knowledge in vascular plants, enables to investigate the evolution of SL cellular pathways in land plants. In angiosperms, the perception of SLs relies on a receptor called D14 (encoded by the same gene family as KAI2) along with the F-box protein MAX2. In moss, Max2 is not required for the SL response although it possesses 13 KAI2-like genes (PpKAI2L). An unusual aspect of SL perception is that the D14 protein is both a receptor and an enzyme that cleaves its substrate (and covalently binds part of the SL) in a signaling mechanism that is still under debate. To further investigate whether PpKAI2L proteins play roles as receptors of SLs and related compounds, we examined the covalent attachment of the artificial SL GR24 isomers to the PpKAI2L proteins by mass spectrometry (MS). Analyses revealed 96 Da increments (corresponding to the D ring mass) when AtKAI2 and PpKAI2L were incubated with GR24 isomers indicating that moss PpKAI2L proteins, like vascular plant receptors, covalently link GR24 enantiomers. As SL signaling is not conserved in P. patens, it appears that the known SL signaling pathway results from a vascular plants specific innovation. Likewise, SL response in P. patens would be the product of a convergent evolution. Therefore, the question as to how P. patens transduces the SL signal, downstream of perception by specific PpKAI2L proteins, remains open. This work was conducted by a team of INRAE (Sandrine Bonhomme) in collaboration with other teams of french institute (ICSN) and laboratory (LBPV). Mass spectrometry analyses were performed at the I2BC proteomics platform.

More information here.

Contact person: David Cornu

Intergenic ORFs of S. cerevisiae encode the elementary building bricks of protein structures and can provide the raw material for de novo gene birth and protein evolution. 

The noncoding genome plays an important role in de novo gene birth and in the emergence of genetic novelty. Nevertheless, how noncoding sequences’ properties could promote the birth of novel genes and shape the evolution and the structural diversity of proteins remains unclear. In this work, in collaboration with Namy's team, IMPMC and DSIMB lab, we show that the Intergenic ORFs (Open Reading Frames) of S. cerevisiae encode the elementary building bricks of protein structures and can provide the raw material for de novo gene birth and protein evolution. In particular, we show that the noncoding genome contain a vast amount of Intergenic ORFs encoding foldable peptides. The latter can serve as starting points for de novo gene emergence or be integrated into pre-existing proteins, thus contributing to protein modularity and participating in protein evolution. Then, we investigated the early stages of de novo gene birth by reconstructing the ancestral sequences of 70 yeast de novo genes and characterized the sequence and structural properties of intergenic ORFs with a strong translation signal. This enabled us to highlight sequence and structural factors determining de novo gene emergence. In particular, we showed that ancestral intergenic ORFs and highly translated intergenic ORFs are enriched in ORFs encoding peptides with a strong folding potential, thereby giving a central role to protein foldability in the emergence of new genes. Finally, we showed a strong correlation between the fold potential of de novo proteins and one of their ancestral amino acid sequences, reflecting the intimate relationship between the noncoding genome and the protein structure universe.

BSI 2021 is presenting special sessions:  

"Science & Société : La parole scientifique dans l'espace public": Many questions have raised by the period we have just passed through concerning the place of scientific speech in public debate, the role of experts (or so-called), interactions between researchers/experts, the media, politicians and the public. This roundtable will seek to shed light on what could/should be the contribution of researchers to public debates and the conditions for this contribution to be effective.

"Session étudiants": UPSaclay students are invited to attend the morning sessions and meet up with researchers. Free but registration required HERE.

"Satellite event - Alpha Fold": With the advent of AlphaFold, the BSI welcomes you to a round table meeting to discuss the impact and opportunity offered by this revolutionary tool. Free but registration required HERE.

Further information and details on how to access the conference location can be found on the BSI 2021 website.

Nature’s trick in conversion of light into chemical energy is revealed when an artificial photo-synthetic model showed evidence of intermediate state pertaining to functionality of electron relay in controlling unidirectional flow and accumulation of charges.

In photosynthesis, Photosystem II is the enzyme that captures sunlight to drive the four-electron, four-proton oxidation of water. It contains a series of co-factors in a defined setup to convoy electrons in a vectorial fashion from the initial locus of light excitation to accumulate charges at the catalytic unit. A pair of Tyr and His amino acids plays a decisive role as relay between the P680 chlorophyll, the primary photooxidant, and the Mn4Ca water oxidizing catalyst (WOC) as it couples the one-photon, one-electron photochemistry of the light absorber to multi-electronic catalysis. A “rocking proton” mechanism operating between these two residues has been identified as a crucial feature of this electron relay. Implementing such functionalities in chemical modular assemblies may help chemists to gain control over the directionality of electron transfer when developing molecular systems for artificial photosynthesis.
Gotico et al. have investigated a set of molecular triads holding a photosensitizer, an imidazole as redox relay, and a monometallic manganese complex as a proxy for a WOC. Time-resolved spectroscopy coupled with the electrochemical properties has permitted to track the formation of an imdazolyl radical, initiated from the photooxidized chromophore, and its subsequent decay connected to oxidation of the Mn(II) site. Comprehensive analysis of the thermodynamic and kinetic parameters reveal the importance of the acid-base properties of this electron relay and highlight the crucial role of reversible proton transfer to allow the system to display a light-induced two-step electron hopping process. This study sets the path for further optimization in the directional electron transfer and charge accumulation for using photons to drive the oxidation of water.

More information here.

Contact person: Winfried LEIBL

Imagerie-Gif and CNRS Formation Entreprises are organizing a training to blow your mind with flow cytometry.

We offer you to acquire the theoretical bases in flow cytometry (analysis and sorting, experimental strategies), to be informed of applications and developments in very varied fields of application, and to initiate or deepen the use of analyzers and sorters.
The training will be split in theoretical mornings and practical afternoons. Practical afternoons will take place on GIF and ORSAY campus.
The training is opened to Student, researcher and Engineer.

https://cnrsformation.cnrs.fr/atelier-cytometrie?mc=Cytom%C3%A9trie

Contact person: BOURGE Mickael

The ICSN and the I2BC are the two major units of the CNRS campus of Gif sur Yvette.

The “institut de Chimie des substances naturelles” (ICSN), with a staff of nearly 150 people, is the chemistry pole of the CNRS campus in Gif sur Yvette. This unit develops activities at the chemistry-biology interface, with natural substances as the object of study and main source of inspiration. Equipped with numerous platforms, including two NMR platforms, the ICSN will host an NMR apparatus from an I2BC team when it moves from the CEA-Saclay to the Gif-sur-Yvette campus. However, the links between our two institute are not limited to NMR; the purpose of this first morning is to introduce you to ICSN in the hope of encouraging new collaborations.

This first Morning-Meeting, which will be the first of a series, will be oriented towards the platforms of the two units and duos of researchers to illustrate the fruitful collaborations already in place.

Please come in large numbers to meet your chemical colleagues.

Due to health conditions, the meeting will be held in hybrid mode, both in the auditorium of Building 21 on the Gif-sur-Yvette campus and on Zoom.

See program on the website: here

Contact for link: communication@i2bc.paris-saclay.fr

appelsprojetsrecherche.fr est un portail à destination des acteurs de la recherche. Inscrit dans le cadre de la Loi de Programmation de la Recherche, il est porté aujourd’hui par six partenaires : l’Ademe, l’ANR, l’ANRS, l’ANSES, l’INCa et l’Inserm. Il offre ainsi un accès unifié aux appels à projets ou à candidatures à venir et en cours, pour une plus grande visibilité de l’offre de financement. Après la date de clôture, les appels restent publiés encore quelques mois.

The 2nd french congress on integrative structural biology took place on november29th-December 3rd at the Centrale Supelec building, located on the Paris- Saclay plateau. Co-organized by the Association Française de Cristallographie and the Société Française de Biophysique, it brought together over 250 participants of which 63 students.

The program of the event included 13 sessions covering health issues, DNA/RNA world, membrane proteins, intrinsically disordered proteins, macromolecular assemblies. Several round tables allowed discussions about “formation tout au long de la vie”, ” interactions entre académie/industrie”, ” infrastructures” and “la parole scientifique dans l’espace public”. A satellite event on the revolutionnary tool AlphaFold ended up the congress.

Many thanks to the institutional partners (CNRS, CEA, I2BC, ICSN, Ecole Polytechnique, ENS Paris-Saclay, FRISBI, IRRMN, Université Paris-Saclay , Université Paris-Saclay Graduate School Life Sciences and Health, Synchrotron SOLEIL, France-Bioimaging) and industrial partners (Bruker, Cytiva, CytobodX, Dynamic Biosensors, Eurisotop, GenScript, Horiba, Innova-Chem, Jeol, NMR-Bio, Refeyn, Sanofi, Servier, Sptlabtech , Thermofisher, et Twist ) for their support.

Congratulations to Magda Teixeira Nunes and and Luce Dreno who won the best poster prize of the AFC and SFB, respectively!

BSI website

Contact person: Julie Ménétrey

This fall, the I2BC welcomed its 36 new doctoral students on December 13, 2021. 2020-21 was the the “white” class, 2021-22 is the”blue” class. After a presentation by Frederic Boccard on the research fields of I2Bc and its technological platforms, the doctoral students were able to meet YourI2BC, the association of young researchers from I2BC. the association organizes social and scientific events throughout the year, mainly aimed at young researchers from the I2BC.

The “Blue Class” is made up of 36 new doctoral students in six doctoral schools of the University of Paris-Saclay, the two main ones being ED 577 (structure and dynamics of living systems) and ED 569 (therapeutic innovation). Despite the difficulties encountered since the start of the COVID-19 pandemic, 13 students come from abroad. Finally, the doctoral students are divided into teams belonging to the 5 disciplinary departments of the I2BC: 10 doctoral students in each of the B3S, Genome Biology and Microbiology departments and 4 and 2 doctoral students in the Cellular Biology and Virology departments respectively.
Welcome to the new PhD class of I2BC!

More information : YourI2BC

Towards a therapy against cerebral malaria?

Cerebral malaria is a neuroinflammatory disease caused by the parasite Plasmodium falciparum. Dr Sylviane Pied's team at the Center of Infection and Immunity of Lille (Inserm U1019-CNRS UMR9017) in collaboration with that of Dr Stanistlas Tomavo, Institute for Integrative Biology of the Cell (CNRS UMR 9198-CEA, Université Paris Saclay) identified an original mechanism explaining the disease. Researchers have shown that the transfer of parasitic microvesicles to astrocytes occurs through an unconventional autophagy mechanism and causes these cells to malfunction. Astrocytes are well known for their role in the integrity of the blood brain barrier. Using a preclinical model and pharmacological drugs, the researchers succeeded in inhibiting the entry of parasitic microvesicles into astrocytes. Thus, the function of astrocytes is restored during infection leading to protection against cerebral malaria. This major discovery could have applications in humans. The results of this study were published in the journal Autophagy. 2021 Nov 6:1-16. doi: 10.1080/15548627.2021.1993704. PMID: 34747313.

 More information here.

Contact person: Stanislas Tomavo

Unveiling how bacteria modify the surface of solid walls in their close environment at the nanoscale is an important step in nanotechnology and bioengineering as well as in geomicrobiology and fundamental surface chemistry/physics.

Bacteria have evolved on earth for billions of years and have managed to colonize all ecological niches. Their metabolic diversity is so vast that they play a major role in the biogeochemical cycles of our planet. Understanding the mechanisms by which bacteria interact with the first interfacial layers of the solid matter that surrounds them is an important issue with many perspectives in both fundamental and applied science. Thin iron films, with a surface area of centimeters and a thickness of nanometers, have been produced. The nanofilm’s opacity being related to its thickness, it is then possible to measure both the nanofilm’s degradation and to localize and quantify the bacteria dynamics in situ and in real time by simple optical means (backgroud of the picture). This experimental work published in the journal ACS Central Science indicates a homogeneous corrosion of iron nanofilms triggered suddenly by bacteria. Experiments reveal in particular rapid motions of Shewanella oneidensis MR1 bacteria during iron dissolution. Mutants of S. oneidensis as well as other bacterial species such as E. coli and L. plantarum are also able to induce corrosion (figure). All the experiments highlight more generally the role of electroactive respiratory proteins and soluble secreted molecules in the modification of the surface properties of nanofilms.

More information here.

Contact person: Christophe Regeard

The transcriptional regulation of the biosynthesis and resistance to netropsin is not only controlled by a transcriptional regulator, Cgc1, but also by netropsin itself, which induces the expression of the resistance genes and of cgc1 by a new type of feedforward induction mechanism.

Understanding the mechanisms of regulation of specialized metabolite production can have important implications both at the level of specialized metabolism study (expression of silent gene clusters) and at the biotechnological level (increase of the production of a metabolite of interest). We report here the first study on the regulation of the biosynthesis of a metabolite from the pyrrolamide family, congocidine (netropsin). Most pyrrolamides bind into the minor groove of DNA, specifically in A/T-rich regions, which gives them numerous biological activities, such as antimicrobial and antitumoral activities. We demonstrate that Cgc1, a cluster-situated, atypical orphan response regulator, controls congocidine biosynthesis and resistance. In addition, we show that congocidine induces the expression of the operon containing the resistance genes, offering protection against congocidine to cells that are not yet producing it. Finally, our results reveal that congocidine induces its own biosynthesis through the induction of the transcription of cgc1, in a new type of feed-forward induction mechanism.

More information here.

Contact person: Sylvie Lautru

A PhD student (Université Paris-Saclay) unveils her comic strip, illustrated by Marine Spaak, and invites you to dive into the heart of scientific research on HIV !

Like the book "Sciences en bulles", presented at the "Fête de la Science", the "Diagonale Paris-Saclay" challenged our doctoral student, Lisa Bertrand, to explain and share her thesis in a fun way in the form of a comic strip. His topic? Defining the translatome of HIV-1 in order to identify new antigens recognized by T-cells.
She followed several introductory sessions that taught her how to synthesize her ideas, turn them into a playful script, choose illustrations to complete her remarks, until she got a first storyboard. The illustrator Marine Spaak accompanied her throughout this process and then took it upon herself to shape all these ideas! Discover their image and immerse yourself in the world of the ribosome, a small cellular constituent responsible for protein production.You will find there that the AIDS virus hijacks ribosomes for its own benefit to make its own viral proteins. And how French research explores this phenomenon, in order to develop therapies. In addition to therapeutic research, the study of viruses is an excellent tool for understanding the functioning of the cell.
The comic on :
http://www.sciencesociete.universite-paris-saclay.fr/decouvrir/la-recherche-sort-de-sa-bulle/#section_3