Tau is a protein regulating microtubule dynamics which also forms neurofibrillary tangles in pathological conditions. Recent results suggest that a physiological dimer of Tau could serve as a nucleus for its aggregation.

Tauopathies are a group of neurodegenerative diseases characterized by the presence of insoluble filaments of the Tau protein in the brain. In physiological conditions, Tau is involved in the regulation of microtubule dynamics. The study of its interaction with different tubulin assemblies, using various experimental approaches, leads to a seemingly disparate picture. In this opinion-type article, we integrate this information into a model of how Tau participates in microtubule assembly and stabilization. Related to its intrinsically disordered nature, the binding of Tau to microtubules involves both specific interactions, along protofilaments, and non-specific ones, with the C-terminal region of tubulin subunits. In addition, a Tau:tubulin structure that we recently determined leads to a model of a functional Tau dimer targeting a microtubule aperture between protofilaments. This model also provides a framework for a Tau aggregation that would be initiated on the microtubule.

More information : https://www.jbc.org/article/S0021-9258(26)01958-7/fulltext

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

In Arabidopsis, RMA ion channel is a candidate for mediating cytosolic calcium signaling in response to high frequency mechanical stimulation.

Plants respond to mechanical stimuli by a rapid increase in cytosolic calcium. The intensity and kinetics of the calcium changes define calcium signatures important for biological responses. In this study carried in the BioCell department of I2BC , we determine the properties of a calcium-permeable force-gated channel localized at the plasma membrane called Rapid Mechanically Activated (RMA).

Using patch clamp and pressure clamp, we characterized the kinetics of the Arabidopsis thaliana RMA channel upon stimulation by pressure pulses applied onto the plasma membrane. Combining pressure pulse protocols at different frequencies with modeling, we investigated the channel's capacity to transduce high frequency mechanical stimuli.
The RMA channel rapidly activates in response to membrane tension, then it inactivates during prolonged stimulation. Upon repeated stimulations, the RMA current amplitude decreases irreversibly indicating that it undergoes attenuation. The channel kinetics were modeled with four chemical states and the model predicts that it behaves as a pass band filter in the 10 Hz–1 kHz range.

In conclusion, due to its activation/inactivation, the RMA channel is a candidate for mediating cytosolic calcium signaling in response to mechanostimulation. Its attenuation and filtering properties suggest its involvement in the transduction of high frequency mechanical stimulation, such as those produced by insects' vibrations.

More info: http://doi.org/10.1111/nph.71241

Contact: jean-marie.frachisse@i2bc.paris-saclay.fr

A condensin I complex, known for shaping chromosome organization in eukaryotes, is essential to DNA elimination in Paramecium

During development, many organisms eliminate specific germline DNA sequences to shape their somatic genome. But how do cells target which sequences to remove? The team “Programmed Genome Rearrangements” has addressed this question in the ciliate Paramecium tetraurelia. Because of its nuclear dimorphism, this unicellular eukaryote provides a powerful model to study somatic differentiation at the genomic scale. At each sexual cycle, a new somatic macronucleus (MAC), specialized for gene expression, is formed from a copy of the germline micronucleus (MIC), inherited from the previous generation. This process involves the elimination of one third of germline sequences, including transposable elements and satellite DNA, to ensure proper gene function and progeny survival.

In collaboration with scientists from the Institut Jacques Monod, the authors have uncovered a surprising new role for a development-specific condensin I, a complex from the SMC family (Structural Maintenance of Chromosomes) generally known for organizing chromosomes in three dimensions. Using TurboID and protein co-immunoprecipitation, combined with quantitative mass spectrometry, we found that the developmental condensin I complex interacts with the PiggyMac (Pgm) endonuclease, an enzyme essential for cutting and removing specific germline DNA sequences during MAC development. High-throughput sequencing of the DNA extracted from purified new MACs revealed that when cells are depleted of condensin I, the germline genetic material is massively retained in the somatic genome. This demonstrates that condensin I plays a key part in programmed DNA elimination.

This discovery suggests that 3D genome organization may help target which sequences are removed. The condensin complex localizes to the developing new MAC, where it stabilizes Pgm and its partners. However, the exact level at which spatial genome architecture influences PDE remains an open question.

More info: https://doi.org/10.1093/nar/gkag351

Conatct: Mireille Bétermier mireille.betermier@i2bc.paris-saclay.fr

The numerous tiny germline chromosomes of Paramecia end in DNA segments produced over evolutionary time by the activity of Helitron mobile elements. These chromosome ends are eliminated during development of the individual by a novel mechanism.

Many eukaryotes are able to eliminate chromosome segments or even entire chromosomes during somatic differenciation. This programmed DNA elimination process illustrates eukaryotic genome plasticity and raises questions about the underlying molecular mechanisms. Among the unicellular ciliated protozoans, which include paramecia, the somatic and germline fonctions of chromosomes are separated in two distinct nuclei.

The diploid germline nucleus (MIC, ~ 100 Mb in Paramecium) undergoes meiosis and transmits the genetic information between generations. The polyploid somatic nucleus (MAC, ~ 70 Mb) is responsible for gene expression, but is destroyed at each generation, when a new MAC develops from a copy of the MIC.
Identification of the sequences that undergo programmed DNA elimination requires knowledge of the MIC genome sequence. More than 10 years of research involving several University Paris-Saclay teams and platforms has provided chromosome-scale assemblies of MIC DNA for 7 members of the Paramecium aurelia
species complex and a telomere-to-telomere assembly for one of them, P. tetraurelia. The authors show that the MIC genome consists of around 160 tiny chromosomes (300 kb – 1.2 Mb) with the highest meiotic recombination rate ever reported (420 cM/Mb). The assembly revealed that the germline chromosome ends
are eliminated very early during MAC development by a  echanism different from that known to be involved in elimination of other sequences. This terminal genomic compartment contains a new clade of transposable elements (TE) that belong to the Helitron superfamily. These TE are very ancient (having diverged from other Helitron-like elements at the base of the eukaryotic tree) but have remained active in Paramecia. They appear to preferentially insert into telomeric repeats. One exciting perspective of the study is the elucidation of a novel DNA elimination pathway.

Contact: linda.sperling@i2bc.paris-saclay.fr & olivier.arnaiz@i2bc.paris-saclay.fr 

More information: https://link.springer.com/article/10.1186/s12915-026-02584-w

We uncovered how Agrobacterium tumefaciens exploits host carbon resources to colonize tomato, revealing quinic acid catabolism as the critical driver of its gall-specific fitness.

Agrobacterium tumefaciens is a facultative plant pathogen that forms galls on a wide range of hosts and persists in soil, roots and galls through extensive metabolic versatility. Here, we combined genome-wide transposon sequencing (TnSeq), metabolomics and reverse genetics to identify carbon utilisation pathways supporting A. tumefaciens fitness in tomato roots and galls. TnSeq screening across 21 carbon sources, representative of rhizosphere exudates, root metabolites and gall-derived compounds, identified conserved and substrate-specific fitness determinants, including central metabolic enzymes, transporters and previously uncharacterized catabolic genes. Comparison with in planta TnSeq data revealed environment-dependent metabolic requirements, highlighting fluxes through the Entner–Doudoroff pathway, the TCA cycle and gluconeogenesis. Quinic acid catabolism emerged as a major determinant of fitness specifically in galls, where this compound accumulated. Deletion of pcaC (ATU_RS21295/atu4541) impaired growth on quinic and protocatechuic acids and reduced competitiveness during gall colonisation, with no effect in roots. Together, this work provides a system-level framework for understanding how A. tumefaciens exploits plant-derived nutrients in host-associated environments.

More information: https://doi-org.insb.bib.cnrs.fr/10.1111/1462-2920.70311

https://www.i2bc.paris-saclay.fr/equipe-interactions-of-bacteria-with-plants-and-insects/

https://www.i2bc.paris-saclay.fr/sequencing/

Contact: Denis Faure denis.faure@i2bc.paris-saclay.fr

As part of the “Des Plantes et des Hommes” project led by the EUR Saclay Plant Science, a senior high school class visited the I2BC on March 25, 2026. Catherine Grandclément presented the Institute and a lecture on the symbiosis between legume plants and Rhizobium bacteria. The students visited the I2BC greenhouse to search for nodules on the roots of legumes plants before observing them with a macroscope. Finally, the microscopy platform and Amanda Edling de Barros introduced them to a confocal microscope and its use in studying symbiosis.

With their interest in the subject and their fascination with the equipment, we hope we’ve inspired a passion for research!

More information :

Legume-rhizobia Symbiosis : https://www.i2bc.paris-saclay.fr/equipe-interactions-of-bacteria-with-plants-and-insects/

"Des Plantes et des Hommes” project : Des Plantes et des Hommes” project

Pushing Streptomyces engineering to new frontiers! The Samy phage tool targets the chromosome’s farthest terminal regions, rich in specialized metabolite genes, enabling precise integration across strains. A breakthrough for antibiotic production like albonoursin.

Phages are a valuable resource for the genetic engineering of Streptomyces antibiotic-producing bacteria. Indeed, a few integrative vectors based on phage integrase are available to insert transgene at specific genomic loci. Chromosome conformation captures previously demonstrated that the Streptomyces linear chromosome is organized in two spatial compartments: The central compartment encompassing most conserved and highly expressed genes in exponential phase, and the terminal compartments enriched in poorly conserved sequences including specialized metabolite biosynthetic gene clusters. This study introduces a new integrative tool based on a recently described phage, Samy, which specifically targets the terminal compartment of its native host chromosome. Samy is related to PhiC31 phage and, like the latter, encodes a serine integrase. Whereas PhiC31 targets a site generally located near the origin of replication, the Samy integration site is one of the farthest known attB sites from it. The authors demonstrated that the Samy integrase efficiently mediates the specific integration of a non-replicating plasmid in six Streptomyces strains from distinct clades. Bioinformatic analyses revealed that the Samy-attB site is rather conserved, and located in the terminal compartment of most Streptomyces chromosomes. Finally, heterologous expression of the albonoursin biosynthetic gene cluster from the Samy-, PhiC31-, and R4-attB sites yields quantitatively equivalent levels of production, though qualitative differences were observed. Altogether, these results demonstrate that the att-int Samy system expands Streptomyces genetic engineering tools by enabling targeted integration in the terminal chromosomal compartment.

More information: https://doi.org/10.1007/s00253-026-13707-2

Contact: Stéphanie BURY-MONE stephanie.bury-mone@i2bc.paris-saclay.fr

New discovery: a dynamic interplay between axis proteins and cohesins ensures chromosome stability during meiosis in Sordaria.

Faithful chromosome segregation during meiosis requires the coordinated action of cohesin complexes and chromosome axis proteins. How these factors interact and communicate along chromosome axes, especially during meiotic prophase I, remains however, only partially understood. Researchers of the Genome Biology Department of the I2BC investigated the functional interplay between the cohesin components and regulators (Rad21, Rec8, Wapl, Sororin, Spo76/Pds5) and two meiosis-specific axis proteins Red1 and Hop1. Analysis of multiple combinations of their corresponding null mutants and of their genetic-epistasis interactions in the fungus Sordaria macrospora revealed a hierarchical regulatory network for their recruitment and releasing. Their work uncovers an unexpected role of axis proteins Red1 and Hop1, that together with Sororin, provide stage-specific protection of Spo76/Pds5 against Wapl-mediated release. Furthermore, we identify that Spo76/Pds5 is the main target of Wapl and acts as a central guardian of kleisin stability against Slx8/STUbL-dependent proteasomal degradation.

Together, these findings show that a dynamic crosstalk between axis proteins and cohesins is crucial to preserve axis integrity and to ensure accurate meiotic progression.

More information: https://doi.org/10.1371/journal.pgen.1012001

Contact: Stéphanie BOISNARD stephanie.boisnard@i2bc.paris-saclay.fr

Master Unix for bioinformatics with a free, progressive skills sheet and interactive Sandbox.bio tutorials—no install needed! Check it out here: https://sandboxbio.france-bioinformatique.fr/

As data generation in life and health sciences accelerates, mastering core bioinformatics skills—especially Unix command-line proficiency—has become essential. In response, the e-learning working group of the IFB (Institut Français de Bioinformatique), in which Claire Toffano-Nioche from the BIOI2 facility of I2BC participates, developed a progressive Unix skill sheet tailored for life scientists with little or no prior experience, recently published in PLoS Comput Biol. This skills sheet summarises the most commonly used Unix commands in the field of bioinformatics. Skills are organised according to increasing levels of difficulty and thematic groups and are cumulative, meaning that skills acquired at a given level are required at the next level. Each skill has been defined operationally by following Bloom's taxonomy of learning objectives. This framework can be freely reused (CC BY 4.0) - by learners as well as tutors - and serves as inspiration for defining the competencies or prerequisites of a training course, or for evaluating the level of a student.

Following this sheet, the e-learning working group directly implemented progressive, interactive sessions that can be used for self-paced learning or in classroom settings. These sessions are deployed via Sandbox.bio, an open-source platform leveraging WASM (WebAssembly) technology. This ensures seamless access from any browser—no installation required—while enabling computations to run locally on the user’s machine.

To further support self-paced learning, BIOI2 also offers autotraining course materials on their website (https://bioi2.i2bc.paris-saclay.fr/training). These resources draw inspiration from—and contribute back to—multiple open courses, including those from the IFB, creating a collaborative cycle of shared knowledge and continuous improvement.

More information:

• Link towards the article: https://doi.org/10.1371/journal.pcbi.1014133
• Link towards sandboxbio IFB: https://sandboxbio.france-bioinformatique.fr/
• Link towards the skill sheet: https://zenodo.org/records/18686109
• Link towards BIOI2 training page: https://bioi2.i2bc.paris-saclay.fr/training/

Contact: contact-bioi2@i2bc.paris-saclay.fr

In March, the 3rd PizzaTech-Workshop took place—a technico-scientific event organized by the Imagerie-Gif facility of the I2BC. Benoit Maury from Leica Biosystems presented the brand-new THUNDER Imager Cell photonic microscope equipped with a Spinning Disk (CICERO), a setup designed for live cell imaging. This allows the observation of rapid cellular biological phenomena in real-time and 3D, thanks to two key components:

• Optics: The spinning disk provides optical sectioning and reduces phototoxicity.
• Image Processing: The THUNDER application eliminates out-of-focus residual light, enhancing contrast and resolution to reveal finer details.

PizzaTech & Presentation:

After enjoying pizza, researchers explored the technical and functional features of the system, including:

• Confocal spinning disk and widefield modalities, both compatible with THUNDER image processing.
• Key applications: live cells, 3D cultures, organoids, spheroids, thick tissues, and model organisms.

Demo Week on the Photonics Microscopy Facility – Imagerie-Gif:

Researchers, PhD students, and engineers tested the THUNDER Imager Cell / Spinning Disk CICERO with their own samples for a week. The setup included:

• Spinning Disk CICERO module (pinhole size: 50 µm; pinhole spacing: 250 µm; disk rotation speed: ~15,000 rpm; field of view: 22 mm).
• Excitation lasers (405, 470, 555, 640 nm).
• Two sCMOS cameras (Hamamatsu Fusion; Photometrics Kinetix22).
• Inverted microscope (Leica DMi8) with motorized AFC (Adaptive Focus Control).

The system was fully equipped with:

• THUNDER 2D/3D (opto-digital clarification).
• Adaptive Immersion (stabilized water objectives).
• SmartCORR (automatic aberration correction).
• Sample Finder (automatic sample navigation).
• Incubator for live cell imaging.

Participating Research Teams:

• Institut des Neurosciences Paris-Saclay
• I2BC (teams: Giordano / Lipid trafficking and membrane contact sites, Le Clainche / Cytoskeleton dynamics and motility, Kühl / Mammalian mitochondrial gene expression in health and disease, Urvoas / B3S Protein Engineering and Modeling, Imagerie-Gif facility engineers)
• Institut Curie Orsay
• Genethon

Image credits:

1. Esther GIL HERNANDEZ, Equipe de GIORDANO Francesca, ERL INSERM. Lipid trafficking and membrane contact sites
2. Sharbatanu CHATTERJEE & Md Amit HASAN, Institut NeuroPSI - UMR9197, Circuits neuronaux & comportement
3. Aleksandr BALATSKII, Genethon
4. Light Microscopy facility, Imagerie-Gif.

More about the THUNDER Imager Cell Spinning Disk: https://www.leica-microsystems.com/products/light-microscopes/p/thunder-imager-cell-spinning-disk/

More information about the facility: https://www.i2bc.paris-saclay.fr/bioimaging/ 

Thermococcales, hyperthermophilic archaea from hydrothermal vents, promote iron sulfide precipitation, enabling survival in iron-rich environments. Some cells become encrusted in pyrite and do not survive mineralization, while surviving cells activate metal detoxification genes.

Thermococcales, sulfur-reducing archaea inhabiting the hottest parts of hydrothermal vents, have evolved to thrive in environments rich in iron and sulfide species. In this study, using experimental analogues of sulfur-rich hydrothermal chimneys, we confirm previous suggestions that the precipitation of iron sulfide minerals promoted by Thermococcales contributes to a population-wide adaptation to reactive species induced by the presence of high levels of iron. In parallel with mineral phases identification, cellular metabolic activity was monitored during mineralization, revealing a mechanism in which a subpopulation of cells does not survive mineralization and becomes encrusted in pyrite, while the remaining living cells exhibit a gene expression profile focused on DNA repair and metal excess associated detoxification. Compared to abiotic conditions, Thermococcales induce a faster precipitation of dissolved iron, immobilising excess metal. Our results clarify the role of mineralizing cells in this survival mechanism, suggesting that this biomineralization process allows resilience to extreme chemical stress. Upon drastic levels of toxic dissolved iron, thanks to a population of mineralizing cells, the surviving Thermococcales are thus more likely to endure those still harsh environments. This complex mechanism is likely a key factor in the adaptation of microorganisms to the hottest environments of hydrothermal vents.

More information : https://enviromicro-journals.onlinelibrary.wiley.com/doi/10.1111/1462-2920.70242

Contact : Aurore Gorlas  aurore.gorlas@i2bc.paris-saclay.fr

Cyclodipeptide synthases (CDPSs) utilize two aminoacyl-tRNAs as substrates to produce diverse natural products. Here, we demonstrate that CDPSs efficiently recognize aminoacylated microhelices (miHxs) that mimic the tRNA acceptor arm. Structural and enzymological analyses using unacylated, misacylated, and engineered miHxs reveal a shared RNA-binding mode for both substrates. These findings establish miHxs as versatile tools to investigate CDPS function and, more broadly, other aminoacyl-tRNA–dependent enzymes.

Two teams from the I2BC, in collaboration with the ICSN, combined enzymological and structural approaches to investigate cyclodipeptide synthases (CDPSs), enzymes involved in natural product biosynthesis. CDPSs sequentially use two aminoacyl-tRNAs (AA-tRNAs) to catalyse cyclodipeptide formation. We previously showed that microhelices (miHxs), mimicking the tRNA acceptor arm, are as efficient as full-length AA-tRNAs when aminoacylated by flexizymes.
Here, we generated a diverse set of miHxs (acylated, unacylated, misacylated, mutated, or shortened) and analysed their interactions with CDPSs. We focused on the Nocardia brasiliensis CDPS (Nbra-CDPS), which synthesizes cyclo(L-Ala–L-Glu) from Ala-tRNAAla and Glu-tRNAGlu. Crystal structures of Nbra-CDPS bound to analogues of its first substrate, including unacylated and acylated miHxAla, were determined. Cryo-EM analysis confirmed that miHxs mimic the acceptor stem of full-length tRNAs.
We also solved the structure of Nbra-CDPS bound to unacylated miHxGlu, an analogue of the second substrate, and found that it superimposes well with miHxAla despite sequence differences. Together with results obtained using misacylated substrates, these data reveal a shared RNA-binding mode for both substrates. Our findings establish miHxs as powerful tools to dissect CDPS function and to study other AA-tRNA–dependent enzymes.

More information: https://academic.oup.com/nar/article-abstract/doi/10.1093/nar/gkag307/8625897?utm_source=authortollfreelink&utm_campaign=nar&utm_medium=email

Contacts:

Muriel Gondry muriel.gondry@i2bc.paris-saclay.fr

https://www.i2bc.paris-saclay.fr/enzymology-and-non-ribosomal-peptide-biosynthesis/

Jean-Baptiste Charbonnier jb.charbonnier@i2bc.paris-saclay.fr

https://www.i2bc.paris-saclay.fr/nuclear-enveloppe-telomeres-and-dna-repair/

Researchers from the I2BC recently visited Collège A. Fournier in Orsay to introduce students to various scientific career paths. Magali Noiray presented the institute’s state-of-the-art facilities, while Olivier Namy showcased the exciting work of its research teams.

Science is for everyone, and the journey can start at any age. Let’s inspire the next generation of innovators!

More information about I2BC: https://www.i2bc.paris-saclay.fr/ 

A great thanks to Magali & Olivier for their time and commitment!

A functional partnership between a lipid scramblase and a lipid transfer protein in the regulation of phosphatidylserine homeostasis.

Phosphatidylserine is synthesised in the endoplasmic reticulum (ER), but this negatively charged lipid is highly concentrated in the plasma membrane (PM). There, it plays numerous roles in processes such as cell signalling and cell fusion, and it can also mediate apoptosis and synaptic pruning when exposed in the outer leaflet of the PM. In the yeast Saccharomyces cerevisiae, selective PS transport between the ER and the PM by the lipid transfer protein Osh6 is required for PS enrichment in the plasma membrane. Osh6 operates at membrane contact sites (MCS), where it interacts with the Ist2 protein embedded in the ER, tethering the ER to the PM via its long, disordered C-terminal tail.

In two studies conducted in collaboration with the CRBM (CNRS/University of Montpellier), the IPMC (CNRS/University of Nice Côte d'Azur), and the IBCP (CNRS/University of Lyon), we show that Ist2 is a membrane transporter that catalyses rapid lipid exchange across the two leaflets of the ER – acting as a lipid ‘scramblase’ – and that this scrambling activity sustains Osh6-mediated PS transfer between the ER and the PM.

First, we demonstrated that Ist2 catalyses the scrambling of different lipids in vitro after reconstituting purified Ist2 in proteoliposomes. Molecular dynamics simulations were then used to identify a cavity through which the lipid headgroup passes during transport from one leaflet to another. Further cellular studies revealed a close relationship between the COPII complex and the Ist2 protein. This was manifested by impaired yeast growth and vacuolar trafficking, as well as disruption of ER exit sites. We also found that Ist2 deletion stimulates the formation of ER-derived lipid droplets and changes their composition. Finally, using artificial, reconstituted ER-PM contact sites, we demonstrated that Ist2-mediated lipid scrambling sustains Osh6-mediated lipid transfer. 

Together, our studies identify Ist2 as a lipid scramblase and establish that lipid scrambling in the ER by Ist2 controls various cellular functions, such as vesicular transport and lipid droplet homeostasis. This highlights the importance of lipid dynamics for ER function. Furthermore, we reveal a functional partnership between Ist2-mediated lipid scrambling and Osh6-mediated lipid transfer at MCS.

More information :

https://doi-org.insb.bib.cnrs.fr/10.1083/jcb.202502112

https://www-science-org.insb.bib.cnrs.fr/doi/10.1126/sciadv.adz2217

Contact : Guillaume Lenoir guillaume.lenoir@i2bc.paris-saclay.fr

NMT in a new light: associated with the ribosome via the NAC complex, this enzyme not only adds lipid tags to the N-termini of nascent proteins but also acts as a chaperone, cooperating with MetAPs to ensure proper folding and delivery.

N-myristoylation is an essential cotranslational lipid modification catalyzed by N-myristoyltransferases (NMTs). Structural and cellular analyses reveal that NMT1 associates with the ribosomal tunnel exit via the nascent polypeptide–associated complex (NAC) and acts sequentially after MetAP-mediated initiator methionine removal, in contrast to previously described simultaneous cotranslational modification assemblies. Unexpectedly, NMT1 also exhibits chaperone-like activity, expanding its functional repertoire in cotranslational protein biogenesis.

More information : https://www-nature-com.insb.bib.cnrs.fr/articles/s41467-025-67962-4

Contact : Thierry Meinnel and Carmela Giglione thierry.meinnel@i2bc.paris-saclay.fr and carmela.giglione@i2bc.paris-saclay.fr