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December 17, 2024 11:56 AM
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DciA, the Bacterial Replicative Helicase Loader, promotes LLPS in the presence of ssDNA.

DciA, the Bacterial Replicative Helicase Loader, promotes LLPS in the presence of ssDNA. | I2BC Paris-Saclay | Scoop.it

This study shows that DciA, the bacterial replicative helicase loader, promotes condensates in the presence of DNA. This opens the way to the possibility of non-membrane compartments in bacteria. The goal could be to concentrate the players involved in replication and thus facilitate it.

The loading of the bacterial replicative helicase DnaB is an essential step for genome replication and depends on the assistance of accessory proteins. Several of these proteins have been identified across the bacterial phyla. DciA is the most common loading protein in bacteria, yet the one whose mechanism is the least understood. We have previously shown that DciA from Vibrio cholerae is composed of a globular domain followed by an unfolded extension and demonstrated its strong affinity for DNA. Here, drawing on the skills of two I2BC facilities, Light microscopy (Imagerie-Gif) and PIM (Structural biology), we characterize the condensates formed by VcDciA upon interaction with a short single-stranded DNA substrate. We demonstrate the fluidity of these condensates using light microscopy and address their network organization through electron microscopy, thereby bridging events to conclude on a liquid-liquid phase separation behavior. Additionally, we observe the recruitment of DnaB in the droplets, concomitant with the release of DciA. We show that the well-known helicase loader DnaC from Escherichia coli is also competent to form these phase-separated condensates in the presence of ssDNA. Our phenomenological data are still preliminary as regards the existence of these condensates in vivo, but open the way for exploring the potential involvement of DciA in the formation of non-membrane compartments within the bacterium to facilitate the assembly of replication players on chromosomal DNA.

More information : https://pubmed.ncbi.nlm.nih.gov/39603490/

Contact : Sophie CHERUEL sophie.quevillon-cheruel@i2bc.paris-saclay.fr  and Stéphanie MARSIN stephanie.marsin@i2bc.paris-saclay.fr

 

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December 9, 2024 3:44 AM
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Ribosome composition plays a key role in EMT

Ribosome composition plays a key role in EMT | I2BC Paris-Saclay | Scoop.it

Ribosome remodeling drives cancer cell transformation: A single protein, RPL36A, triggers EMT.

Epithelial-mesenchymal transition (EMT) is a biological process whereby a cell loses its usual characteristics to acquire properties allowing it to move. EMT is involved in embryo formation and tissue repair in adults. However, when altered, EMT contributes to the formation of fibrosis or, in the case of a tumor cell, to the formation of metastases. In cancers, this change is comparable to a cellular metamorphosis that allows cancer cells to become more aggressive and resistant to treatments. EMT is therefore a key player in tumor progression.
EMT is extensively studied at the molecular and cellular levels because a better understanding of this process will enable the development of new therapeutic approaches. However, the translational changes that occur during EMT have so far been very poorly studied.
In this work, we have identified that the overexpression of a single ribosomal protein, called RPL36A, is sufficient to induce EMT. We have also highlighted the various translational changes that occur during EMT.
Our work reveals the importance of ribosome remodeling itself in finely modulating translation during the change in cellular identity that occurs during EMT.

More information : https://www.pnas.org/doi/10.1073/pnas.2408114121 ; In French: https://www.insb.cnrs.fr/fr/cnrsinfo/des-modifications-de-la-composition-du-ribosome-accompagnent-les-changements.

Contact: Olivier NAMY olivier.namy@i2bc.paris-saclay.fr

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December 4, 2024 8:19 AM
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Portrait Jeune Chercheur – Christopher Dane Fage, Chercheur en biochimie structurale

Portrait Jeune Chercheur – Christopher Dane Fage, Chercheur en biochimie structurale | I2BC Paris-Saclay | Scoop.it

Christopher Dane Fage is a structural biochemist who, in January of 2024, joined the Institute for Integrative Biology of the Cell - I2BC (CNRS/CEA/UPSaclay, Gif-sur-Yvette) as a CNRS CRCN to lead the team Structures and functions of hybrid natural product assembly lines. His research seeks to understand and exploit the biosynthesis of medically relevant bacterial metabolites by multi-family enzyme systems.

 

In 2014, Chris earned his PhD from the University of Texas at Austin (USA) in the team of Adrian Keatinge-Clay, where his interest in the structural biochemistry of polyketide synthases (PKSs) crystallized (these multi-domain, multi-module enzymatic assembly lines build complex molecules from simple building blocks through the catalytic chemistry of fatty acid synthases (FASs)). For example, from the spinosyn insecticide pathway, he investigated a Diels-Alderase-like enzyme (catalyzes a reaction widely used in chemical synthesis) and a “dimerization element” (organizes the modular architecture of many PKSs).

 

Subsequently, as a postdoc at Philipps-Universität Marburg (Germany) with Mohamed Marahiel, Chris focused on other types of natural product-forming enzymes, such as non-ribosomal peptide synthetases (NRPSs; these assembly line systems incorporate different building blocks than PKSs using different catalytic domains). For example, he initiated an integrative structure-function study on the inter-subunit “COM” interfaces needed for efficient peptide formation in many NRPSs. He also studied the properties, detection, biosynthesis, and tailoring of the ribosomally synthesized and post-translationally modified lasso peptides, which adopt a remarkably stable lariat knot-like fold. 

 

From 2017, Chris joined the teams of Greg Challis and Józef Lewandowski at the University of Warwick (UK). There, he investigated trans-AT PKSs, which employ a wide variety of standalone enzymes in place of their subunit-embedded counterparts, as well as hybrid PKS-NRPS systems, which merge the catalytic chemistry of PKSs and NRPSs – thanks to their peculiarities, these machineries build exceptionally diverse compounds. He also clarified the mode of action of the kalimantacin antibiotics against the human pathogen Staphylococcus aureus.

 

In a brief departure from natural products, Chris worked at the Centre for Medicines Discovery at the University of Oxford (UK) during 2022-2023, where he characterized the structures of three enzymes associated with type 2 diabetes mellitus. He also developed a high-throughput assay for screens against libraries of tens of thousands of inhibitors.

 

Since arriving at the I2BC, Chris has been pursuing structure-guided studies towards the rational reprogramming of hybrid FAS-NRPS-PKS systems, with particular interest in those of the kalimantacin (antibacterial) and bleomycin (anticancer) drugs.

 

“The true delight is in the finding out rather than in the knowing.” - Isaac Asimov

 

-> Contact : christopher.fage@i2bc.paris-saclay.fr


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November 26, 2024 3:25 AM
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Bioorthogonal monomycolate of trehalose disclosed the O-mycoloylation of mycoloyltransferases and other cell envelope proteins in C. glutamicum

Bioorthogonal monomycolate of trehalose disclosed the O-mycoloylation of mycoloyltransferases and other cell envelope proteins in C. glutamicum | I2BC Paris-Saclay | Scoop.it

Discovering the mycoloylome of Corynebacterium glutamicum : a new type of lipidated-modified proteins.

Protein mycoloylation is a lipidation pathway exclusively observed in Mycobacteriales, an order of bacteria that includes several human pathogens. These bacteria possess a distinctive outer membrane, known as the mycomembrane, composed of very long-chain fatty acids called mycolic acids. It has been demonstrated that a few mycomembrane proteins undergo covalent modification with mycolic acids in the model organism Corynebacterium glutamicum, through the action of mycoloyltransferase MytC. This PTM represents the first example of protein O-acylation in prokaryotes and also the first example of protein modification by mycolic acid. Here, we have developed a unique bioorthogonal mycolate donor featuring the natural mycolic acid pattern, enabling direct unambiguous transfer of the lipid moiety to its acceptors and efficient metabolic labeling and enrichment of MytC protein substrates. Mass spectrometry analysis of the labeled proteins and comparative proteomic analysis of the cell envelope proteome between wild-type and ∆mytC strains identified an unbiased list of 21 proteins likely mycoloylated in the cell. The robustness of our approach is demonstrated by the successful biological validation of mycoloylation in 6 random candidate proteins within wild-type cells, revealing the characteristic profile of proteins modified with natural mycolates. These findings provide interesting insights into the significance of this new lipidation pathway and pave the way for understanding their function, especially concerning the mycoloyltransferase family that includes the essential Antigen85 enzymes in Mycobacteria.

More information: https://doi.org/10.1021/acschembio.4c00502.

Contact: Cécile LABARRE <cecile.labarre@i2bc.paris-saclay.fr>

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November 19, 2024 3:50 AM
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MatP local enrichment delays segregation independently of tetramer formation and septal anchoring in Vibrio cholerae

MatP local enrichment delays segregation independently of tetramer formation and septal anchoring in Vibrio cholerae | I2BC Paris-Saclay | Scoop.it

The study of Vibrio cholerae MatP reveals the degree of integration of the plasmid-derived chromosome carried by the bacterium, and suggests that the ancestral role of MatP is to promote cell division at the end of the chromosome replication and segregation cycle.

V. cholerae harbours a primary chromosome derived from the monochromosomal ancestor of the Vibrionales (ChrI) and a secondary chromosome derived from a megaplasmid (ChrII). The coordinated segregation of the replication terminus of both chromosomes (TerI and TerII) determines when and where cell division occurs. ChrI encodes a homolog of Escherichia coli MatP, a protein that binds to a DNA motif (matS) that is overrepresented in replication termini. Here, we use a combination of deep sequencing and fluorescence microscopy techniques to show that V. cholerae MatP structures TerI and TerII into macrodomains, targets them to mid-cell during replication, and delays their segregation, thus supporting that ChrII behaves as a bona fide chromosome. We further show that the extent of the segregation delay mediated by MatP depends on the number and local density of matS sites, and is independent of its assembly into tetramers and any interaction with the divisome, in contrast to what has been previously observed in E. coli.

More information: https://www.nature.com/articles/s41467-024-54195-0

Contact: E. Galli elisa.galli@i2bc.paris-saclay.fr

& FX Barre francois-xavier.barre@i2bc.paris-saclay.fr

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November 18, 2024 4:12 AM
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Cafés de la GS LSH - 22 novembre 2024 avec Denis Faure

Cafés de la GS LSH - 22 novembre 2024 avec Denis Faure | I2BC Paris-Saclay | Scoop.it

Le prochain café se tiendra le vendredi 22 novembre 2024 en visioconférence de 13h30 à 14h avec la participation de Denis Faure (I2BC) qui nous parlera sur « The versatile lifestyle of the plant pathogen Agrobacterium tumefaciens »

 

Pour assister en visioconférence : ICI


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November 6, 2024 3:29 PM
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Conference: Single-cell & Spatial-omics

Conference: Single-cell & Spatial-omics | I2BC Paris-Saclay | Scoop.it

The Graduate School Life Sciences & Health of the Université Paris-Saclay organizes a scientific day about Single-cell & Spatial-omics.

On Tuesday the 19th of November, the Graduate School Life Sciences and Health (GS LSH) of the Université Paris-Saclay is organizing its 8th scientific day, which is dedicated to “Single-cell and spatial-omics”. During the symposium, speakers from Université Paris-Saclay institutes and elsewhere will present their work involving single-cell and spatial -omics technologies. As part of the day, I2BC team leaders Kasia Siudeja and Joana Santos will present their work on the aging process in Drosophila and the infection cycle of the Malaria parasite. The day will take place in the Henri Moissan building on the Université Paris-Saclay campus. Participation is free, but registration is mandatory.

Registration: https://forms.office.com/e/6T3rVgPAYE

More information: https://openagenda.com/fr/universite-paris-saclay/events/journee-scientifique-gs-lsh-single-cell-and-spatial-omics

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October 30, 2024 8:53 AM
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The next-generation sequencing—chess problem

The next-generation sequencing—chess problem | I2BC Paris-Saclay | Scoop.it

By comparing the collection of Next-Generation Sequencing data to the superimposition of several chess games, we demonstrate the limits of current temporal analysis approaches.

The development of next-generation sequencing (NGS) technologies paved the way for studying the spatiotemporal coordination of cellular processes along the genome. However, data sets are commonly limited to a few time points, and missing information needs to be interpolated. Most models assume that the studied dynamics are similar between individual cells, so that a homogeneous cell culture can be represented by a population-wide average. Here, we demonstrate that this understanding can be inappropriate. We developed a thought experiment—which we call the NGS chess problem—in which we compare the temporal sequencing data analysis to observing a superimposed picture of many independent games of chess at a time. The analysis of the spatiotemporal kinetics advocates for a new methodology that considers DNA-particle interactions in each cell independently even for a homogeneous cell population.

More information: https://academic.oup.com/nargab/article/6/4/lqae144/7833696

Contact: Julie Soutourina julie.soutourina@i2bc.paris-saclay.fr

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October 17, 2024 6:14 AM
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Introduction to biological crystallography

Introduction to biological crystallography | I2BC Paris-Saclay | Scoop.it

Following the French MOOC 'Voyage au cœur du vivant avec des rayons X : la cristallographie', available on FUN-MOOC from 2017 to 2022, and the book in French 'Introduction à la cristallographie biologique', we now present an English version.

Following the French MOOC 'Voyage au cœur du vivant avec des rayons X : la cristallographie', available on FUN-MOOC from 2017 to 2022, and the book in French 'Introduction à la cristallographie biologique', we now present an English version.
This book is primarily designed for beginners in biological crystallography.
It provides an introduction to the different steps of biological crystallography, from the crystallisation to the three-dimensional structure of a macromolecule. The QR codes at the end of each chapter give you access to the videos in French, that are part of the MOOC. English subtitles are available for all the videos. In the early stages of learning biological crystallography, the digital version of this book can therefore be a particularly useful companion.

 - Marie-Hélène Le Du, Pierre Legrand, Serena Sirigu, Sylvain Ravy - EDP Sciences & Science Press Introduction to biological crystallography

link: https://bit.ly/3zBC6p5

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October 17, 2024 6:06 AM
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Plant Science Day October 17th

Plant Science Day October 17th | I2BC Paris-Saclay | Scoop.it

Gif-sur-Yvette B22 N001

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October 17, 2024 5:56 AM
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DciA secures bidirectional replication initiation in Vibrio cholerae

DciA secures bidirectional replication initiation in Vibrio cholerae | I2BC Paris-Saclay | Scoop.it

DciA secures bidirectional replication initiation in Vibrio cholerae.

Replication is initiated bidirectionally in the three domains of life by the assembly of two replication forks at an origin of replication. This is made possible by the recruitment of two replicative helicases to a nucleoprotein platform built at the origin of replication with the initiator protein. The reason why replication is initiated bidirectionally has never been experimentally addressed due to the lack of a suitable biological system. Using genetic and genomic approaches, we show that upon depletion of DciA, replication is no longer initiated bidirectionally at the origin of replication of Vibrio cholerae chromosome 1. We show that following unidirectional replication on the left replichore, nascent DNA strands at ori1 anneal to each other to form a double-stranded DNA end. While this DNA end can be efficiently resected in recB+ cells, only a few cells use it to trigger replication on the right replichore. In most DciA-depleted cells, chromosome 1 is degraded leading to cell death. Our results suggest that DciA is essential to ensuring bidirectional initiation of replication in bacteria, preventing a cascade of deleterious events following unidirectional replication initiation.

More information: https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkae795/7759985

Contact: Amelie BESOMBES amelie.besombes@i2bc.paris-saclay.fr

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October 17, 2024 5:45 AM
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De Novo Emerged Gene Search in Eukaryotes with DENSE

De Novo Emerged Gene Search in Eukaryotes with DENSE | I2BC Paris-Saclay | Scoop.it

DENSE with your favorite genome and uncover its de novo genes! Try our fully automated tool for DE Novo gene SEarch and discover useful metrics to help design your search!

The recent discovery of de novo emerged genes, which originate from previously noncoding regions of DNA, challenges traditional views of species evolution. Indeed, the hypothesis of neutrally evolving sequences giving rise to functional proteins is highly unlikely. However, the accumulation of sequencing data revealed that they are widespread, being detected in various eukaryotic species and numerous, with several dozens of examples reported for different organisms. This conundrum has sparked numerous studies to quantify and characterize these genes, aiming to understand their functional roles and contributions to genome evolution. Yet, no fully automated pipeline for their identification is available. Therefore, we introduce DENSE (DE Novo emerged gene SEarch), an automated Nextflow pipeline based on two distinct steps: detection of taxonomically restricted genes (TRGs) through phylostratigraphy, and filtering of TRGs for de novo emerged genes via genome comparisons and synteny search. DENSE is available as a user-friendly command-line tool, while the second step is accessible through a web server upon providing a list of TRGs. Highly flexible, DENSE provides various strategy and parameter combinations, enabling users to adapt to specific configurations or define their own strategy through a rational framework, facilitating protocol communication, and study interoperability. We apply DENSE to seven model organisms, exploring the impact of its strategies and parameters on de novo gene predictions. This thorough analysis across species with different evolutionary rates reveals useful metrics for users to define input datasets, identify favorable/unfavorable conditions for de novo gene detection, and control potential biases in genome annotations. Additionally, predictions made for the seven model organisms are compiled into a requestable database, which we hope will serve as a reference for de novo emerged gene lists generated with specific criteria combinations.

More information: https://academic.oup.com/gbe/article/16/8/evae159/7745841

Contact: Anne LOPES anne.lopes@i2bc.paris-saclay.fr

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October 2, 2024 3:59 AM
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Les Visites insolites du CNRS à l'I2BC

Les Visites insolites du CNRS à l'I2BC | I2BC Paris-Saclay | Scoop.it

Une expérience surprenante avec les sciences! Les Visites insolites du CNRS vous proposent chaque année des expériences uniques, en groupe restreint, au cœur des laboratoires de recherche pour vivre des moments privilégiés avec les scientifiques.

Si on vous dit « microbes » ou « bactéries », vous pensez généralement aux pathogènes, causes de nombreuses maladies et de grandes épidémies dans l’histoire de l’humanité (peste, lèpre, tuberculose…) ? Et pourtant, les micro-organismes ne sont pas toujours nos ennemis, certaines bactéries sont même à l’origine de nombreux antibiotiques ! Si lors de leurs découvertes dans les années 1950-1970, nous avons cru gagner la bataille contre les bactéries pathogènes, ces dernières résistent et ne sont plus sensibles aux antibiotiques actuels. Alors comment recherche-t-on de nouveaux antibiotiques ? Comment étudie-t-on les bactéries qui les fabriquent ? Quels sont les mécanismes de résistance des bactéries pathogènes ? Peut-on faire fabriquer de nouveaux antibiotiques à des bactéries ? Venez découvrir la réponse à certaines de ces questions au travers d’observations et de discussions avec des membres du laboratoire !

more information: https://visitesinsolites.cnrs.fr/visite/sous-la-loupe-du-laboratoire-secrets-et-defis-des-antibiotiques/

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December 16, 2024 5:49 AM
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Epigenetic control of T-DNA during transgenesis and pathogenesis

Epigenetic control of T-DNA during transgenesis and pathogenesis | I2BC Paris-Saclay | Scoop.it

T-DNAs are mobile elements transferred from pathogenic Agrobacterium to plants that reprogram host cells into hairy roots or tumors, and which are used as disarmed forms to deliver transgenes in plants. Here we review the mechanisms that silence the expression of T-DNAs in transgenic plants as well as during pathogenesis.

Mobile elements known as T-DNAs are transferred from pathogenic Agrobacterium to plants and reprogram the host cell to form hairy roots or tumors. Disarmed nononcogenic T-DNAs are extensively used to deliver transgenes in plant genetic engineering. Such T-DNAs were the first known targets of RNA silencing mechanisms, which detect foreign RNA in plant cells and produce small RNAs that induce transcript degradation. These T-DNAs can also be transcriptionally silenced by the deposition of epigenetic marks such as DNA methylation and the dimethylation of lysine 9 (H3K9me2) in plants. Here, we review the targeting and the roles of RNA silencing and DNA methylation on T-DNAs in transgenic plants as well as during pathogenesis. In addition, we discuss the crosstalk between T-DNAs and genome-wide changes in DNA methylation during pathogenesis. We also cover recently discovered regulatory phenomena, such as T-DNA suppression and RNA silencing-independent and epigenetic-independent mechanisms that can silence T-DNAs. Finally, we discuss the implications of findings on T-DNA silencing for the improvement of plant genetic engineering.

More information: https://academic-oup-com.insb.bib.cnrs.fr/plphys/advance-article/doi/10.1093/plphys/kiae583/7876130

Contact: Angélique DELERIS angelique.deleris@i2bc.paris-saclay.fr

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December 4, 2024 11:38 AM
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The structure of a Tau fragment bound to tubulin prompts new hypotheses on Tau mechanism and oligomerization

The structure of a Tau fragment bound to tubulin prompts new hypotheses on Tau mechanism and oligomerization | I2BC Paris-Saclay | Scoop.it

We have identified a novel tubulin surface targeted by the Tau protein. From these results, we formulate new hypotheses on the regulation of microtubules by Tau and on Tau oligomerization.

Tau is a protein involved in the regulation of axonal microtubules in neurons. In pathological conditions, it forms filamentous aggregates which are molecular markers of the Alzheimer’s disease and of related neurodegenerative disorders collectively known as tauopathies. Structures of Tau in fibrils or bound to the microtubule have been reported. We have determined the structure of a Tau construct comprising the PHF6 motif, an hexapeptide involved in Tau aggregation, as a complex with tubulin. This Tau fragment binds as a dimer to a new site which, when transposed to the microtubule, would correspond to a pore between protofilaments. These results raise new hypotheses on Tau-induced microtubule assembly and stabilization and on Tau oligomerization. They reconcile apparently contradictory data from the literature, in particular concerning the coexistence of different binding modes of Tau to the microtubule.

More information : https://academic.oup.com/pnasnexus/article/3/11/pgae487/7850850

Contact : Benoît GIGANT benoit.gigant@i2bc.paris-saclay.fr

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November 26, 2024 3:28 AM
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Perylene-derivative singlet exciton fission in water solution

Perylene-derivative singlet exciton fission in water solution | I2BC Paris-Saclay | Scoop.it

Ultrafast formation of triplet statates by singlet fission in water solution.

We provide evidence that singlet fission—a process where one excited state splits into two—can occur in water-soluble compounds. Specifically, we studied perylene-3,4,9,10-tetracarboxylate, a molecule that forms transient disordered dimers. Using a combination of advanced techniques like time-resolved absorption and fluorescence spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and theoretical modeling, we were able to detect the key features of singlet fission and map out the behavior of the molecular assemblies. Our results show that the constant structural changes within these dimers play a crucial role in steering the process toward either singlet fission or charge separation. The quantum efficiency of producing triplet states is over 100%, with these states lasting for nanoseconds—highlighting how disordered systems can drive highly efficient photophysical processes.

More information: https://pubs.rsc.org/en/content/articlehtml/2024/sc/d4sc04732j

Contact: Manuel LLANSOLA <manuel.llansola@I2bc.paris-saclay.fr>

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November 26, 2024 3:23 AM
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Talin and vinculin combine their activities totrigger actin assembly

Talin and vinculin combine their activities totrigger actin assembly | I2BC Paris-Saclay | Scoop.it

In cells, focal adhesions (FAs) strengthen their connection with the actin cytoskeleton to resist force. By combining biochemistry and cell biology, the authors show that the proteins talin and vinculin control actin assembly, thus reinforcing the anchoring of actin to FAs.

Focal adhesions (FAs) strengthen their link with the actin cytoskeleton to resistforce. Talin-vinculin association could reinforce actin anchoring to FAs bycontrolling actin polymerization. However, the actin polymerization activity ofthe talin-vinculin complex is not known because it requires the reconstitutionof the mechanical and biochemical activation steps that control the associa-tion of talin and vinculin. By combining kinetic and binding assays with singleactinfilament observations in TIRF microscopy, we show that the associationof talin and vinculin mutants, mimicking mechanically stretched talin andactivated vinculin, triggers a sequential mechanism in whichfilaments arenucleated, capped and released to elongate. In agreement with these obser-vations, FRAP experiments in cells co-expressing the same constitutivemutants of talin and vinculin revealed accelerated growth of stressfibers. Ourfindings suggest a versatile mechanism for the regulation of actin assembly inFAs subjected to various combinations of biochemical and mechanical cues.

More information: https://www.nature.com/articles/s41467-024-53859-1

Contact: Christophe LE CLAINCHE <christophe.leclainche@i2bc.paris-saclay.fr>

 
 
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November 19, 2024 3:27 AM
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The ribosome profiling landscape of yeast

The ribosome profiling landscape of yeast | I2BC Paris-Saclay | Scoop.it

We explored the ribosome profiling landscape of yeast and showed that noncoding regions are associated with a wide diversity of translation signals among which some led to detectable protein products.

Pervasive translation is a widespread phenomenon that plays a critical
role in the emergence of novel microproteins, but the diversity of translation patterns contributing to their generation remains unclear. Based on 54 ribosome profiling (Ribo-Seq) datasets, we investigated the yeast Ribo-Seq landscape using a representation framework that allows the comprehensive inventory and classification of the entire diversity of Ribo-Seq signals, including non-canonical ones. We show that if coding regions occupy specific areas of the Ribo-Seq landscape, noncoding regions encompass a wide diversity of Ribo-Seq signals and, conversely, populate the entire landscape. Our results show that pervasive translation can, nevertheless, be associated with high specificity, with 1055 noncoding ORFs exhibiting canonical Ribo-Seq signals. Using mass spectrometry under standard conditions or proteasome inhibition with an in-house analysis protocol, we report 239 microproteins originating from noncoding ORFs that display canonical but also non-canonical Ribo-Seq signals. Each condition yields dozens of additional microprotein candidates with comparable translation properties, suggesting a larger population of volatile microproteins that are challenging to detect. Our findings suggest that non-canonical translation signals may harbor valuable information and underscore the significance of considering them in proteogenomic studies. Finally, we show that the translation outcome of a noncoding ORF is primarily determined by the initiating codon and the codon distribution in its two alternative frames, rather than features indicative of functionality. Our results enable us to propose a topology of a species’ Ribo-Seq landscape, opening the way to comparative analyses of this translation landscape under different conditions.

More information: https://genomebiology.biomedcentral.com/articles/10.1186/s13059-024-03403-7

Contact: Anne Lopes  anne.lopes@i2bc.paris-saclay.fr

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November 18, 2024 4:11 AM
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Conférence : "One Health challenge to control vector borne diseases" - Mercredi 27 novembre 2024 de 9h15 à 12h15 à Henri Moissan

- Are you interested in Parasitology?

or

- Would you like to discover a field of research at the interface between Biology and Chemistry?

or

- Would you like to discover new research methods or study models?

 

Come and attend the Workshop:

 

Practical information:

  • Date: 11/27/2024
  • Times: 9.15 a.m. to 12.15 p.m. (detailed program above)
  • Address: Bâtiment Henri Moissan, 17, avenue des Sciences, 91400 ORSAY, France
  • Room: 2000 (HM1 building)
  • Program and theme (details attached): 3 parasitology specialists come to talk about their latest research findings on malaria and leishmaniasis. Come and listen to their lectures and have lunch with them.
  • Registration (deadline 11/20/2024): registration is free but compulsory by clicking on this link
  • Module validation: This seminar could validate a doctoral school module for doctoral students.

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November 3, 2024 12:00 PM
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Reference-free exploration of cancer RNA datasets

Reference-free exploration of cancer RNA datasets | I2BC Paris-Saclay | Scoop.it

Bioinformaticians finds new ways to analyze cancer RNA in very large datasets

Cancer cells produce an immense diversity of RNA molecules. Using deep sequencing technologies, scientists explore these RNAs to uncover key insights into cancer onset and progression. However, cancer RNA datasets are becoming so large that directly searching them for a given sequence is impossible. Currently, scientists must rely on simplified representations, such as gene expression tables. Yet, many cancer-causing RNAs are absent from standard gene expression tables. The Transipedia consortium, bringing together bioinformaticians from I2BC/University Paris-Saclay, University of Lille, and University of Montpellier, introduces a new approach to mining RNA-seq databases using k-mer indexes. In their latest paper, they demonstrate that an index of 1,019 cancer cell lines can be queried in real time while providing accurate quantification of cancer mutations, fusions, or splicing variants. In future work, the consortium plans to expand this technology to offer access to an even larger database of cancer and normal tissues, aiming to accelerate cancer genomics research.

More information: https://genomebiology.biomedcentral.com/articles/10.1186/s13059-024-03413-5

Contact:  Daniel Gautheret daniel.gautheret@i2bc.paris-saclay.fr

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October 29, 2024 5:36 AM
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Novel, tightly structurally related N-myristoyltransferase inhibitors display equally potent yet distinct inhibitory mechanisms

Novel, tightly structurally related N-myristoyltransferase inhibitors display equally potent yet distinct inhibitory mechanisms | I2BC Paris-Saclay | Scoop.it

Peptides fitting the optimal human NMT Gly-myristoylation recognition pattern act as potent inhibitors. Lys-myristoylation-based inhibitors from these peptides were designed. Each series’ inhibitory properties are unique, relying on distinct interactions.

N-myristoyltransferases (NMTs) catalyze essential acylations of N-terminal alpha or epsilon amino groups of glycines or lysines. Here, we reveal that peptides tightly fitting the optimal glycine recognition pattern of human NMTs are potent prodrugs relying on a single-turnover mechanism. Sequence scanning of the inhibitory potency of the series closely reflects NMT glycine substrate specificity rules, with the lead inhibitor blocking myristoylation by NMTs of various species. We further redesigned the series based on the recently recognized lysine-myristoylation mechanism by taking advantage of (i) the optimal peptide chassis and (ii) lysine side chain mimicry with unnatural enantiomers. Unlike the lead series, the inhibitory properties of the new compounds rely on the protonated state of the side chain amine, which stabilizes a salt bridge with the catalytic base at the active site. Our study provides the basis for designing first-in-class NMT inhibitors tailored for infectious diseases and alternative active site targeting.

More information: https://www-cell-com.insb.bib.cnrs.fr/structure/abstract/S0969-2126(24)00318-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0969212624003186%3Fshowall%3Dtrue

Contact: Thierry Meinnel thierry.meinnel@i2bc.paris-saclay.fr

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October 17, 2024 6:08 AM
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Cell Mechanotransduction and Microbial Invasion Symposium

Cell Mechanotransduction and Microbial Invasion Symposium | I2BC Paris-Saclay | Scoop.it

Learn with great scientists about cell mechanotransduction and microbial invasion processes

Morning session: Cell Mechanotransduction 9H00-9H30 : Christophe Leclainche, I2BC, Gif-sur-Yvette.
Understanding mechanotransduction through in vitro reconstitution of actomyosin-dependent protein machineries
9H30-10H00 : Benoit Ladoux, MPZPM, Erlangen, Germany.
Mechanical imprints of cell extrusion from epithelial tissues.
10H00-10H30 : Patricia Bassereau, Institut Curie, Paris.
Cell spreading on fluid membranes requires strong integrin ligands and microtubules
10H30-10H50 : Coffee break
10H50-11H20: Gregory Giannone, Université de Bordeaux.
Unraveling the nanoscale spatial and mechanical regulation of actin binding proteins.
11H20-12H00 : Keynote lecture - Michael Sheetz, UTMB, Texas, USA.
Mechanical Oscillations Kill Cancer Cells and Reverse Aging
 
Afternoon session « Microbial Invasion»

14H00-14H30 : Sven Hammerschmidt, Greifswald university, Germany
TBA
14H30-15H00 :  Sandrine Bourdoulous, Institut Cochin, Paris.
Angptl4 prevents endothelial dysfunction during bacterial sepsis
15H00-15H40 : Keynote lecture - Linda Kenney, UTMB, Texas, USA.
Imaging Salmonella Lifestyles: From Virulence to Biofilms to Tumors
15H40-16H00 : Coffee break
16H00-16H30 : Jost Enninga, Institut Pasteur, Paris.
Endomembrane breakage by enteroinvasive bacterial pathogens- new insights by in cellulo structural biology
16H30-17H00 : Marc Prudhomme, Université Paul Sabatier, Toulouse
Bacterial communication and antibiotic tolerance in Pneumooccus
17H00-17H30 : Guy Tran Van Nhieu, I2BC, Gif-sur-Yvette.
Characterization of pneumococcal secreted factors associated with bacterial meningitis

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October 17, 2024 6:00 AM
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Symposium Archaea October 17-18 2024

Symposium Archaea October 17-18 2024 | I2BC Paris-Saclay | Scoop.it

more information: https://archaea2024.sciencesconf.org/

Contact: tamara.basta@i2bc.paris-saclay.fr

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October 17, 2024 5:54 AM
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The acetyltransferase SCO0988 controls positively specialized metabolism and morphological differentiation in the model strains Streptomyces coelicolor and Streptomyces lividans.

The acetyltransferase SCO0988 controls positively specialized metabolism and morphological differentiation in the model strains Streptomyces coelicolor and Streptomyces lividans. | I2BC Paris-Saclay | Scoop.it

Acetylation of some proteins plays a positive role in the regulation of the production of specialized metabolites and in the morphological differentiation of Streptomyces.

Streptomyces species possess in their genomes numerous silent biosynthetic pathways likely to direct the biosynthesis of novel bioactive specialized metabolites. Enhancing the expression of these cryptic pathways might lead to the discovery of most needed novel antibiotics to limit the spreading of pathogenic bacteria resistant to most antibiotics in current use.
We characterized, an acetyl transferase (SCO0988) whose over-expression led to enhanced antibiotic production and accelerated sporulation of a low antibiotic producing strain, Streptomyces lividans, while the deletion of this gene had opposite effects in a strong antibiotic producer, Streptomyces coelicolor. Comparative analysis of the acetylome of the S. lividans strain overexpressing SCO0988 with that of the original strain revealed that 92 peptides, belonging to various proteins involved in different cellular processes, were exclusively acetylated in the strain over-expressing SCO0988. This led to the definition of a consensus SCO0988 acetylation site (v/q-P-l/g-D-p/e-KR-v/l-h/f-y/a-t/m). Among the acetylated proteins, BldKB was found to be over-acetylated on four lysine residues including Lys425 in the strain overexpressing SCO0988. BldKB is the solute binding protein of an ABC transporter involved in the up-take of an oligopeptide that plays a role in the triggering of a quorum sensing regulatory cascade controlling positively specialized metabolism, aerial mycelium formation and sporulation in S. coelicolor. A bldKB mutant has a reduced antibiotic production and does not develop aerial mycelium. The bldKB mutant phenotypes can be complemented by the native bldKB gene but not by a variant of this gene encoding a protein in which Lys425 was replaced by Arg (that cannot be acetylated) or by Glu (a putative structural analogue of acetylated lysine). Our study thus demonstrated that Lys425 is critical for BldKB function but could not clearly establish the impact of Lys425 acetylation on BldKB function.

More information: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303876/

Contact: Marie-Joëlle VIROLLE marie-joelle.virolle@i2bc.paris-saclay.fr

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October 17, 2024 5:43 AM
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A complex and dynamic redox network regulates oxygen reduction at photosystem I in Arabidopsis

A complex and dynamic redox network regulates oxygen reduction at photosystem I in Arabidopsis | I2BC Paris-Saclay | Scoop.it

A system of redox enzymes facilitates a series of reactions that regulate oxygen reduction at photosystem I in plants.

In a study published in Plant Physiology, scientists from I2BC and IPS2 studied the redox regulation of superoxide production at the photosynthetic electron transfer level (pseudocyclic flow). Plants must optimise their molecular strategies to adapt to the light conditions of their environment. Reactive oxygen species (ROS) can play a role as signalling molecules but can also be potentially harmful. To manage light-induced ROS and maintain proper photosynthetic function, thiol-dependent redox enzymes play a crucial role in the redox regulation of the chloroplast. It has been shown that the main redox enzymes involved in controlling the ROS generated during photosynthesis are m-type thioredoxins, NADPH-dependent reductase C (NTRC) and peroxiredoxin 2-Cys. The interaction of these enzymes functions as a redox regulatory network, where 2-Cys PRX can be reduced by NTRC and Trx but can also re-oxidise the reduced thioredoxins, thus providing a system for rapid acclimatisation to changes in the light regime. The researchers showed that the membrane localisation of Trx m and NTRC varies as a function of photoperiod. In addition, their results show that it is the PSI itself that is redox regulated. The new results of this study make it possible to generate a new model of PSI redox regulation. This model may guide further research into the redox regulation of alternative electron transport pathways under conditions of fluctuating light or abiotic stress.

More information: DOI: 10.1093/plphys/kiae501 

Contact: Anja KRIEGER-LISZKAY anja.liszkay@i2bc.paris-saclay.fr

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