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Lundi 22 Avril 2024    0:00
L'objectif général du 6ème cours de biologie cellulaire et de cancérologie est de couvrir différents sujets de biologie cellulaire et de physique, en se concentrant sur la mécanique des tissus, l'effet de mémoire et le métabolisme cellulaire. Le cours couvrira des sujets tels que la polarité cellulaire, la mécanique tissulaire, la mémoire cellulaire et tissulaire, le métabolisme cellulaire et tissulaire, l'optogénétique et les outils de biologie moléculaire.
Centre de recherche - Paris - Amphitheatre Helene Martel-Massignac (BDD)
Lundi 22 Avril 2024    11:00
My lab is dedicated to discovering how the immune system controls cancer and how it can be harnessed for therapeutic purposes. Our work has helped identify how certain cancers are regulated by various immune cells, including cytotoxic T-cells, regulatory T-cells, macrophages, monocytes, neutrophils and dendritic cells, all of which are considered drug targets in cancer immunotherapy. Here I will talk about the coordination of microenvironmental (immune) components that control human cancers.
Tags: Swiss Cancer Centre, SCCL, Geneva University Hospitals, Pittet, Ludwig Cancer Research, Geneva, Mikael Pittet
Annonce publiée le 22-02-2024
Institut Curie
Hopital site de Paris - Amphitheatre Constant-Burg - 12 rue Lhomond, Paris 5e
Lundi 22 Avril 2024    11:00
Invite par: Hugues Aschard The department of Computational Biology will be organizing new Methods Primer seminar series addressing advanced analytical methods. The meetings will be in-person only using a chalk talk format. It aims at being an open ... Plus d'infos...
Tags: Molecular biology, Bioinformatics, DNA replication, Polymerase chain reaction, Primer, Computational biology, Christian Vestergaard
In many animals, mature sperm chromatin is organized with sperm-specific chromosomal proteins known as protamines. Complete or partial elimination of nucleosomes occur during the histone-to-protamine transition, a complex chromatin reorganization process that takes place during spermiogenesis, the differentiation of post-meiotic spermatids. Although protamines are generally thought to play a critical role in sperm chromatin compaction, their actual function remains mysterious. Through the analysis of a rare Drosophila paternal effect mutant named paternal loss (pal), we have discovered that the removal of histones in insect sperm is critical to maintain the epigenetic identity of paternal chromosomes at fertilization. Sperm from pal mutant males aberrantly retain H3-H4 tetrasomes without affecting their ability to fertilize eggs. However, at fertilization, pal chromosomes are mistaken for maternal chromosomes and engage into a deleterious pseudo-meiotic division, leading to the sporadic loss of paternal chromosomes in the early embryo. I will also present our unpublished characterization of a new paternal effect mutant with a pal-like phenotype and discuss our findings in the context of sperm chromatin evolution in animals.
au College de France - Salle D2
11 place Marcelin Berthelot - 75005 Paris
Mardi 23 Avril 2024    11:30
Explainable machine learning approaches are well suited to flexibly and efficiently capture different aspects of organization in spatial omics data and offer a more detailed view of the underlying tissue biology. We developed MISTy, a scalable multi-view machine learning framework, to enable versatility of analysis by combining different types of complex spatially resolved data with prior knowledge. Our explainable models are used for data exploration and generation of hypothesis based on robust structural and functional relationship patterns in the data captured within different spatial contexts, ranging from the subcellular to the broader tissue context. With our newest development, Kasumi, we offer a novel perspective for capturing the heterogeneity of tissues by identification of spatially localized, persistent niches of relationships. Kasumi outperforms related approaches and offers new insights and explanations on the spatial coordination and multivariate relationships underlying the differences in observed progression and response in cancer.
Centre de recherche - Paris - Amphitheatre Constant-Burg - 12 rue Lhomond, Paris 5e
Mercredi 24 Avril 2024    8:00
Location: Institut Pasteur A symposium and workshop on Multimodal Data Analysis for Immunology. Symposium (April 24): Open lectures showcasing how data analysis, statistical modeling, and artificial intelligence approaches can be applied to diverse datasets ... Plus d'infos...
Tags: Scientific method, Formal sciences, Data analysis, Artificial intelligence, Analysis
Annonce publiée le 20-01-2024
Institut Pasteur
Mercredi 24 Avril 2024    9:00
Location: Institut Pasteur A symposium and workshop on Multimodal Data Analysis for Immunology. Symposium (April 24): Open lectures showcasing how data analysis, statistical modeling, and artificial intelligence approaches can be applied to diverse datasets ... Plus d'infos...
Invite par: Sonia GAREL et Nathalie SPASSKY - Section Biologie du Developpement Plus d'infos...
Tags: Senescence, Life extension, Transhumanism, Rejuvenation, Aging brain, Anne Brunet, Software aging, Lifespan Extension Advocacy Foundation
Annonce publiée le 01-04-2024
IBENS
salle Favard, IBENS 46 rue d'Ulm 75005 Paris
Mercredi 24 Avril 2024    11:30
Giant unilamellar vesicles (GUVs) are widely used as in vitro model membranes in biophysics and as cell-sized containers in synthetic biology. Despite their ubiquitous use, there is no one-size-fits-all method for their production. Numerous methods have been developed to meet the demanding requirements of reproducibility, reliability, and high yield, while simultaneously achieving robust encapsulation. Emulsion-based methods are often praised for their apparent simplicity and good yields; hence, methods like continuous droplet interface crossing encapsulation (cDICE) that make use of this principle, have gained popularity. However, the underlying physical principles governing the formation of GUVs in cDICE and related methods remain poorly understood. To this end, we have developed a high-speed microscopy setup that allows us to visualize GUV formation in real-time. Our experiments reveal a complex droplet formation process occurring at the capillary orifice, generating both larger droplets and, likely, GUV-sized satellite droplets. According to existing theoretical models, the oil-water interface should allow for crossing of all droplets, but based on our observations and theoretical modelling of the fluid dynamics within the system, we find a size-selective crossing of GUV-sized droplets only. Finally, we demonstrate that proteins in the inner solution affect GUV formation by increasing the viscosity and altering lipid adsorption kinetics.
Centre de recherche - Paris - Amphitheatre Marie Curie
Jeudi 25 Avril 2024    0:00
In the mouse, disruption of the Planar Cell Polarity (PCP) pathway is associated with congenital heart defects including double outlet right ventricle (DORV). This severe malformation disrupts the double blood circulation because both the aorta and pulmonary artery are connected to the right ventricle. Yet, its embryonic origin has remained unclear. In the fly embryo, the PCP pathway coordinates cells in the plane of epithelia. Inactivation of the core PCP component Vangl2 in the mouse was shown to disrupt elongation of the outflow tract in the embryonic heart tube associated with incomplete heart looping. We now address the mechanisms of heart looping defects in mutants for VANGL2 and its effector SHROOM3. 3D quantifications of heart shape and of cell architecture in the field of heart precursors, suggest that OFT shortening is not the cause of heart looping defects. Our analyses also highlight a novel role of the PCP pathway in modulating cell rearrangements in the heart field epithelium, with no planar polarity of VANGL2. Overall, our work provides novel insights into the role of the PCP pathway during heart morphogenesis relevant to congenital heart defects. Invited by Suzanne Faure-Dupuy, Alberto De la Iglesia and Hugo Barreto, as part of the Post-doc seminar series. Plus d'infos...
The neural crest is an embryonic cell population whose migratory behavior has been likened to cancer invasion during metastasis. Neural crests differentiate into a wide array of cell types, including muscle, cartilage, bones, melanocytes, neurons, and glia. Although the role of mechanical cues has been demonstrated in the migration and differentiation of neural crest cells, little is known about whether mechanics play any role in their early formation.
Neural crest cells are formed through a process called 'embryonic induction,' which involves an interaction between signaling and responding tissues, leading to a change in the direction of differentiation in the responding tissue. Considerable progress has been made in identifying inductive signals, yet how tissues control their responsiveness to these signals, known as competence, remains poorly understood. While the role of molecular signals in competence has been studied, the influence of tissue mechanics on competence remains unexplored.
In this seminar, I will present our recent results showing that neural crest competence decreases concomitantly with an increase in the hydrostatic pressure of the blastocoel, an embryonic cavity in contact with the prospective neural crest. By manipulating hydrostatic pressure in vivo, we demonstrate that this increase leads to the inhibition of YAP signaling and impairs Wnt activation in the responding tissue, which is required for neural crest induction. Furthermore, we show that hydrostatic pressure controls neural crest induction in amphibian and mouse embryos and in human cells, suggesting a conserved mechanism across vertebrates. Our work elucidates how tissue mechanics can interact with signaling pathways to regulate embryonic competence.
Invite par: Chris BOWLER - Section Ecologie et Biologie de l’Evolution As in other eukaryotes, the plant genome is functionally organized in two mutually exclusive chromatin fractions, a gene-rich and transcriptionally active euchromatin, and a gene-poor, repeat-rich, and transcriptionally silent heterochromatin. Maintaining sharp boundaries between these chromatin domains with antagonistic functionalities is therefore essential for transcriptional control and involves chromatin insulators that remain largely unknown in plants. I will present the participation of a plant topoisomerase in such an insulator-like function, which prevents the spreading of heterochromatin marks into euchromatin and thus safeguards gene expression in euchromatin islands. Based on the identification of new partners of the topoisomerase, I will discuss possible mechanisms to this insulator-like function. Plus d'infos...
While the current view states that Transcription Factors (TFs) act on DNA regulatory elements to deploy precise gene programs, an emerging concept proposes that TFs also bind RNA and regulate splicing to promote molecular and cellular diversity. Yet, how the RNA regulatory functions of TFs contribute to their key role in cell fates remains puzzling. From in vitro interaction to tissue development, the seminar will survey some of our latest findings focusing on the splicing function and RNA-binding ability of the homeodomain TFs, using Drosophila muscle development as a paradigm of cell fate decisions.
Tags: Gene expression, Transcription, Transcriptional regulation, Cis-regulatory element
Annonce publiée le 16-02-2024
Institut Curie
Centre de recherche - Orsay - Salle polyvalente du Batiment 111
Vendredi 26 Avril 2024
Invited by the Borghi, Marie Breau (CRCN INSERM, Institut de Biologie Paris-Seine (IBPS), Sorbonne Universite, Laboratoire de Biologie du Developpement) will present an Institut Jacques Monod Seminars on the theme: Mechanical interactions between tissues during the morphogenesis of the zebrafish olfactory placode Abstract: Neuronal circuit assembly requires neuronal migration and axon/dendrite growth, which are believed to be primarily guided by chemical cues. Yet the movement of neurons and their protrusions is influenced by mechanical cues, whose functions have started to be studied in vitro, but remain largely unexplored in vivo. During development, neurons are embedded in neuroepithelia or neuronal clusters (placodes, ganglia) which undergo morphogenetic reorganisation in coordination with surrounding tissues. These adjacent tissues can exert pushing or pulling forces on the neuronal cell bodies or their growing protrusions, thus influencing the final position of the neurons, but also their morphology and connectivity. Conversely, growing neurons or groups of neurons may influence the morphogenesis of nearby tissues through the transmission of forces. I will present how we investigate the role and mechanisms of this kind of tissue-tissue mechanical interplay using as a model the zebrafish olfactory circuit, which develops in the olfactory placode in a superficial location allowing easy live imaging and mechanical perturbations. The seminar will take place on Friday, April 26th at 11.45 am in room& Francois Jacob. Plus d'infos...
A fundamental part of scientific research is publishing your research findings. But once you have submitted your paper to a journal, it can seem like a daunting black box regarding what actually happens to your paper and how authors can successfully navigate the various steps of the publication process. In this presentation, I will share my experience as an editor at Nature to demystify the editorial procedures at a high-profile journal, including insight into what editors look for, and how authors can best respond to the challenges of the publication system (such as peer review). Life as an editor is a fascinating job to have, so I will also highlight aspects relevant to anyone who might be interested in pursuing an editorial career. The session will be intentionally informal, with early-career researchers particularly welcome. Please feel free to bring your own questions and I will be delighted to answer any queries you have.
Tags: Behind the Scenes, Publishing, A Peep Behind the Scenes
Annonce publiée le 18-04-2024
Institut Curie
Centre de recherche - Paris - Amphitheatre Helene Martel-Massignac (BDD)
Lundi 29 Avril 2024    11:00
Invite par: Hugues Aschard The department of Computational Biology will be organizing new Methods Primer seminar series addressing advanced analytical methods. The meetings will be in-person only using a chalk talk format. It aims at being an open ... Plus d'infos...
Tags: Molecular biology, Bioinformatics, DNA replication, Polymerase chain reaction, Primer, Computational biology
Annonce publiée le 11-04-2024
Institut Pasteur
Batiment Yersin, salle Yersin Building ground floor meeting room (24-RDC-02),
How randomly injured animals can appropriately re-establish positional information and control the deployment of repair programs are key questions of regenerative biology. The hydrozoan jellyfish Clytia hemisphaerica has recently emerged as an original model organism for probing repair phenomena, thanks to its remarkable regenerative abilities. Coping with frequent injuries in the planktonic environment, Clytia efficiently restores its circular morphology within 12 hours and regenerates missing structures, such as the mouth, in 4 days. Our investigations uncovered a complex interplay of mechanical forces, cellular migration, and proliferation, underlying this rapid recovery process. During umbrella reshaping, the distinct configurations of the rearranging radial muscle fibres – which can be likened to topological defects - correlate with differential patterns of Wnt signalling activation; they function as positional cues, regulating the fate of the wound and the initiation of organ regenerative programs. Regenerative morphogenesis involves a combination of localized cell proliferation and long-range cell recruitment. Leveraging the unique regenerative process of Clytia, and the recent technological developments of the model, we have started unravelling the mechanical and transcriptional interplay in repairing tissues - combining omics, live imaging, modelling and functional approaches. Our findings not only offer insights into the universal principles governing patterning formation and morphogenesis in physiologically complex adult organisms, but also shed light on the evolutionary trajectories of regenerative capacities and stem cells within metazoans.
Tags: Jellyfish, Regeneration, Common Threads, Thread
Annonce publiée le 18-04-2024
Institut Curie
Centre de recherche - Paris - Amphitheatre Helene Martel-Massignac (BDD)
Jeudi 02 Mai 2024    11:30
Claude Desplan1,2, Nikos Konstantinides1, Felix Simon1, Neset Ozel1, Isabel Holguera1, Jennifer Malin1, Yen Chen1, and Bogdan Sieriebriennikov1
1 Center for Developmental Genetics, Department of Biology, New York University, New York, USA; 2 Center for Genomics and System Biology, NYU Abu Dhabi, UAE.
In the Drosophila optic lobes, ~250 neuronal types organized as 800 columns process the inputs from 800 unit-eyes. Neural stem cells in the medulla sequentially express a series of temporal transcription factors (tTFs), producing at each temporal window different neurons that innervate each of the 800 columns. We used single-cell mRNA sequencing to identify the tTFs that specify most medulla neurons. Each tTF regulates the progression of the series by activating the next tTF and repressing the previous one. Furthermore, the neuroepithelium that generates these stem cells is patterned into subdomains by spatial TFs: Although the series of tTFs is the same in stem cells originating from all spatial domains, the neurons they produce differ. Therefore, the integration of temporal and spatial patterning as well as Notch status, are sufficient to explain the generation of the entire neuronal diversity in this brain region.
Finally, we will show how diversity in the brain can evolve to affect specific sensory functions in different species. I will describe the dramatically increased diversity in the mushroom body in ants as compared to flies, as ants rely extensively on pheromones rather than vision for their eusocial life.
Centre de recherche - Orsay - Amphitheatre du Batiment 111
Jeudi 02 Mai 2024    13:30
Training objectives
- Understand the legal definitions of sexist and sexual violence - Understand the main figures on the subject - Understand the consequences of gender-based and sexual violence - Understand the employer's responsibilities and obligations, as well as sanctions and procedures. - Know how to listen and provide guidance
Tags: Criminology, Violence against men, Violence against women, Sex crimes, Crimes against women, Sexual violence, Initiatives to prevent sexual violence, Causes of sexual violence
Annonce publiée le 06-02-2024
Institut Curie
Centre de recherche - Paris - Webinar
Vendredi 03 Mai 2024    11:00
Aging is associated with a decline in tissue function and the onset of a constellation of diseases. We are interested in understanding aging, with a particular focus on brain aging. Because aging is complex, we use organisms with diverse lifespans – the worm C. elegans, the African killifish, the mouse, and cells from mice and humans. We are interested in identifying epigenetic and metabolic pathways involved in delaying aging in response to external stimuli, including nutrients and the opposite sex. Our lab is also interested in using mouse models to address complex questions about mammalian aging, notably the regulation of regenerative neural stem cells and their progeny during aging. Finally, we are pioneering the naturally short-lived African killifish as a new model to identify principles underlying vertebrate aging and “suspended animation”. We hope that these discoveries will identify new strategies to delay, suspend, or even reverse aspects of aging and age-related diseases.
The Roose team at UCSF studies mechanisms of cell-cell interactions in immunology and cancer1-7, with emphasis on personalized medicine4,8 and single cell approaches9-11. Over the past 7 years, we shifted a large portion of our research efforts to understanding human biology and disease. We are deeply interested in the cellular networks that underpin autoimmune diseases and cancer, which I will talk about in my seminar at the Curie Institute. We “deconstruct” these diseases with single cell technology to generate hypotheses on disease-driving cellular networks.
Through our work on cancer & stem cells, we optimized organoid protocols, propagating, characterizing, and biobanking patient organoids. In my seminar I will cover the organoid pipelines we established in my lab and will present how we are combining these organoids with epithelial cell types together with other patient cell types in assembloids. I will particularly focus on how we are using assembloids to “reconstruct” disease and better understand cancer-immune cell crosstalk. We aim to deconstruct and reconstruct T cell subsets and explore functional T cell programs in the context of cancer metastasis and cancers for which immunotherapy needs to be improved. We believe that assembloids offer many opportunities to make basic research discoveries with direct translational potential.
Tags: Wolfram, Holy Grail, Middle High German literature, Conrad Wolfram, Catherine Wolfram
Annonce publiée le 08-11-2023
Laboratoire Jean Perrin
salle de seminaires 5eme etage - LJP - Tours 32-33
Mardi 21 Mai 2024    11:00
Invite par: Cassandra Koh Keywords: drug abuse, neurodevelopment, extracellular vesicles, basic science Plus d'infos...
Annonce publiée le 29-12-2023
Institut Pasteur
Batiment Jacob, salle Auditorium Francois Jacob,
Mardi 21 Mai 2024    11:00
DNA methylation is a broadly observed epigenetic modification. As genomic DNA methylation profiles dynamically change during development and aging, alterations in DNA methylation patterns are linked to diseases such as cancers and immunodeficiency. ICF syndrome is characterized by hypomethylation at heterochromatin. Of four proteins whose mutation cause ICF syndromes (DNMT3B, ZBTB24, CDCA7 and HELLS), we have previously demonstrated that CDCA7 is a critical activator for the nucleosome remodeling activity of the SNF2-family ATPase HELLS. As DNA methyltransferases cannot directly methylate DNA on the nucleosome, we suggested that the CDCA7-HELLS complex assists DNA methyltransferases by sliding DNA on the nucleosome. However, it remained unclear why the CDCA7-HELLS complex, among several SNF2-family proteins that can remodel nucleosomes, plays a unique role in DNA methylation. Here, I will share our efforts to fill this gap by showing that CDCA7 is an adaptor for hemimethylated CpG. Implications of this finding for diseases will be discussed.
Centre de recherche - Paris - Amphitheatre Constant-Burg - 12 rue Lhomond, Paris 5e
Mercredi 22 Mai 2024    0:00
Les participants auront l'occasion :
Le cours « NON-CODING GENOME » explorera la diversité des éléments d'ADN non géniques et des ARN non codants dans un large spectre de processus cellulaires, chez l'homme et les organismes modèles, ainsi que leur implication dans la physiologie et la pathologie. Des experts de renommée internationale présenteront leurs dernières découvertes relatives à l'identification et à la caractérisation fonctionnelle du génome non codant et discuteront de nouveaux concepts en matière de régulation et d'évolution du génome, en mettant l'accent sur les outils expérimentaux et informatiques. Les sessions thématiques incluront des ARN non codants longs et petits, des éléments transposables, des répétitions d'ADN structurel et des éléments régulateurs non codants. Ce cours offrira aux jeunes étudiants et aux chercheurs l’occasion d’élargir leurs connaissances et de discuter de leurs travaux avec une communauté scientifique internationale dans un environnement stimulant de l’Institut Curie à Paris.
Tags: Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society, Cell and molecular biology
Annonce publiée le 29-02-2024
Institut Cochin
Salle Rosalind Franklin
Jeudi 23 Mai 2024    11:00
Invite par: Emmanuelle FABRE Cells can rapidly and reversibly adopt distinct states and this can occur independently of genetic alterations, a biological mechanism commonly referred to as cell plasticity. CD44 is a plasma membrane glycoprotein associated with development, immune cell activation as well as tumorigenesis. Although often described as a cell-surface marker, the biological function of CD44 remains elusive. We discovered that CD44 mediates the uptake of metals including copper and iron bound to hyaluronates in cells from distinct tissues. This glycan-mediated metal endocytosis mechanism is enhanced during immune cell activation and in cancer cells undergoing epithelialmesenchymal transition. We found that copper(II) catalyzes a previously uncharted chemical reaction in mitochondria required for the production of key metabolites. In contrast, iron is required in the nucleus to promote the activity of specific demethylases. Together, these metals orchestrate metabolic and epigenetic programming of cell plasticity, establishing CD44 as a regulator of cell state transition. We developed new classes of small molecules that selectively interfere with these metal-catalyzed chemical processes in cells. Supformin specifically targets mitochondrial copper(II), thereby antagonizing macrophage activation in several pre-clinical models of acute inflammation and cancer. This validates a key concept in biology whereby pharmacological control of cell plasticity confers therapeutic benefits. This also suggest a competition for metal uptake by immune and cancer cells that may enable tumor progression. Structurally distinct classes of small molecule were developed to manipulate lysosomal iron providing control of cell fate with induction of or protection against ferroptosis . These findings illuminate a universal metal uptake mechanism and the critical role of metals as master regulators of cell plasticity, paving the way towards the development of next generation therapeutics. Plus d'infos...
Annonce publiée le 05-04-2024
UMR7212-U944
Batiment Jean Bernard
INSERM U944 UMR7212
IRSL
Hopital St Louis
16 rue de la Grange aux Belles
75010 PARIS
Vendredi 24 Mai 2024    9:30
Invite par: Hugues de The - College de France Plus d'infos...
Tags: @CirbCdf
Annonce publiée le 18-04-2024
College de France
Amphitheatre Halbwachs, 11 place Marcelin-Berthelot, 75005 Paris
Lundi 27 Mai 2024    9:00
Invite par: Cyril Renassia Annual symposium of the Labex IBEID A day dedicated to the scientific work of the Labex IBEID partners. This year we will have the pleasure to welcome Prof Bernhard Hube from Lebniz-Hans Knoll Institute. ... Plus d'infos...
Tags: Hube, LabEx ReFi - European Laboratory on Financial Regulation, French National Centre for Scientific Research
Annonce publiée le 04-04-2024
Institut Pasteur
Batiment: Duclaux Salle: Amphitheatre Duclaux
Jeudi 30 Mai 2024    0:00
The small interfering RNA pathway constitutes a pivotal antiviral defense against RNA viruses in insects, functioning through RNA interference mediated by Ago2-guided cleavage of viral genomes. This systemic mechanism requires the recognition and transport of double-stranded RNA (dsRNA) of viral origin. Despite the known cellular uptake of dsRNA through endocytosis, the specific protein(s) responsible for this internalization remain elusive. Here, we investigate the role of Hsc70-4, a cytosolic protein known for its chaperone activity, as a potential cell surface receptor or co-receptor for dsRNA internalization in the insect model Drosophila melanogaster. Immunofluorescence assays were conducted on permeabilized and non-permeabilized S2 cells using a specific anti-Hsc70-4 antibody to determine its subcellular localization. Permeabilized cells exhibited cytoplasmic and plasma membrane staining, whereas non-permeabilized cells showed punctate staining on the outer surface of the plasma membrane, indicating the presence of Hsc70-4 in the cell surface. To assess the role of Hsc70-4 as a receptor/co-receptor for dsRNA uptake, we employed immunofluorescence and luciferase-based silencing assays. Pretreatment of S2 cells with anti-Hsc70-4 antibody significantly reduced the internalization of Cy3-labeled dsRNA, suggesting Hsc70-4's involvement in the uptake process. Luciferase assays revealed a direct correlation between antibody concentration during pretreatment and decreased silencing efficiency, further supporting Hsc70-4's role as a dsRNA receptor. Finally, we evaluated the ability of Hsc70-4’s to bind dsRNA in vitro using electrophoretic mobility shift assays and found that Hsc70-4 binds specifically dsRNA in a sequence independent manner. Altogether, our experiments provide evidence that Hsc70-4 is expressed on the cell surface of drosophila cells where it may act as a receptor for extracellular dsRNA. These finding constitutes a previously undescribed function for Hsc70-4, and sheds light on the molecular mechanisms underlying insect antiviral defense. Invited by Suzanne Faure-Dupuy, Alberto De la Iglesia and Hugo Barreto, as part of the Post-doc seminar series. Plus d'infos...
V(D)J recombination is essential for generating the adaptive immune response and unlimited number of different antibodies and antigen receptors. Encoded by multiple V, D and J gene segments, antigen receptors are assembled by programmed double-stranded DNA cleavage and imprecise re-joining. RAG1/2 recombinase initiates the process by stochastically cleaving DNA at a pair of recombination signal sequences (RSS) bordering the V, D or J gene segments. DNA double strand cleavage occurs in a single active site in two consecutive steps, hydrolysis and strand transfer, resulting in DNA hairpin on the coding end and DSB on the RSS side. Coding ends processing and joining to complete V, D, and J gene assembly and circularization of RSS end are carried out by the non-homologous end joining process (NHEJ). The DNA-dependent protein kinase (DNA-PK), consisting of the catalytic subunit (DNA-PKcs) and Ku70/80, is the key player in NJEJ by protecting broken DNA ends, promoting DNA hairpin end opening and also coordinating nucleotide removal, addition and DNA end ligation. In this seminar I will report the molecular mechanism of DNA cleavage by RAG1/2 and regulation of NHEJ by autophosphorylation of DNA-PKcs.
Centre de recherche - Paris - Amphitheatre Marie Curie
Jeudi 06 Juin 2024    0:00
The transcriptional activities of developmental genes in time, in space, or in defined cell-types are orchestrated by repertoires of enhancers that communicate in the 3D nuclear space with target promoters. Transcriptional outcomes, necessary to instruct morphogenesis, also involve defined transcriptional durations over which a gene product exerts its function. This aspect implies that genes’ transcriptional activities are initiated in different cells and trans-environment than the one where they are maintained later on or eventually repressed. Despite this intuitive concept, little is known about the cis-regulatory components that enable it. Here, we have established the regulatory trajectory framework to track how regulatory landscapes control gene transcription in vivo over long developmental time periods. Gene regulatory trajectories first involve transcriptional initiation, which corresponds to the onset of gene expression, followed by maintenance over time, and finally decommissioning, leading to gene repression. Using fluorescent sensors and recorders, we can sort cell populations from embryos at different phases of regulatory trajectories to characterize transcription, chromatin states, and genome topologies. Furthermore, we can engineer complex alleles to assess the role of cis-regulatory regions in controlling the phases of a gene’s regulatory trajectory. In summary, our approach aims to characterize the lifespans of developmental gene regulation and their functional dependencies. Guillaume Andrey is invited by Antoine Zalc. Plus d'infos...
Each limb muscle is unique with a specific shape, size and insertions to bone via connective tissues, so the developmental programs of muscle and associated connective tissues have to be tightly regulated to achieve the final muscle pattern. Although each limb muscle is unique, every muscle displays the same organization, they are all attached to tendons at both extremities and innervated at the center of muscle, defining the muscle domains. We found that muscle fusion is not homogenous within muscle but organized according to these domains. We also identified an unexpected recruitment of fibroblast nuclei in muscle fibers, recruitment localized at muscle tips, close to tendon. The spatial regulation of myogenesis is important to shape limb muscles during development. Delphine Duprez is invited by Pascal Maire. Plus d'infos...
Invite par: Cassandra Koh Keywords: Genome instability, DNA replication, replication stress, centromere, DNA damage Plus d'infos...
Tags: DNA replication, Chromosomes, Molecular genetics, Cell cycle, DNA replication stress, Centromere, Genome instability, S phase, DNA
Annonce publiée le 29-12-2023
Institut Pasteur
Batiment JACOB , salle Auditorium Francois JACOB ,
Jeudi 27 Juin 2024    0:00
Aging is associated with the accumulation of senescent cells and the increase of systemic inflammation. At the cellular level, aneuploidy gradually increases with age, suggesting that centromeric function may be dysregulated during aging, thereby contributing to senescence and inflammaging. Here, we investigated the regulation of centromere integrity in T lymphocytes, which exhibit age-associated aneuploidy and senescent cell accumulation. We have found that resting human lymphocytes from adults harbor a significant population of cells expressing low levels of total CENP-A, while CENP-B and CENP-C levels are not affected. Notably, CENP-A-low cells show lower or non-detectable CENP-A loaded at centromeres, indicating a change in centromere identity. In contrast, T cells from newborns do not exhibit this population. Furthermore, CENP-A-low T cells are not equally distributed among subsets of adult T cells. This indicates that the CENP-A-low state is associated with age-dependent changes and the functional state of T cells. In vitro, activated T cells in which we have recapitulated this defective centromere structure by genetic knock-out of CENP-A, show a senescent phenotype characterized by the upregulation of p53 target genes and the expression of proinflammatory genes. In addition, CENP-A knock-out T cells display chromosome-specific aneuploidy after proliferation. Overall, our results reveal that centromere structure integrity is impacted through lifespan and determines aneuploidy in T cells, contributing to regulation of senescence and inflammation. Invited by Suzanne Faure-Dupuy, Alberto De la Iglesia and Hugo Barreto, as part of the Post-doc seminar series. Plus d'infos...
Tags: Cell biology, Senescence, Chromosomal abnormalities, Cytogenetics, Cells, Cellular senescence, Centromere, Inflammaging, Aneuploidy, T cell, Kinetochore, Tim J. Yen
Annonce publiée le 16-12-2023
Institut Cochin
Salle Rosalind Franklin
Jeudi 04 Juillet 2024    0:00
Facioscapulohumeral muscular dystrophy (FSHD) is a complex neuromuscular disorder characterized by progressive weakness and atrophy of specific groups of muscles. Despite significant advancements in research, elucidating the precise pathophysiological mechanisms underlying FSHD remains a challenging endeavor. To tackle this challenge, we developed an integrated and interdisciplinary approach starting from genotype identification to tissue bioengineering to unravel the intricacies of FSHD pathophysiology.
Leveraging advancements in genomic technologies, we uncovered novel genetic variants and modifiers implicated in FSHD, expanding our understanding beyond the canonical genetic defect.
To complement genotype-based studies, we recently developed tissue bioengineering approaches to recapitulate the FSHD phenotype in vitro.
By considering the diversity of patient’s genotype, this interdisciplinary approach offers a comprehensive framework for dissecting FSHD pathophysiology from a molecular to a cellular level for the identification of the molecular cascades driving disease progression toward the development of treatment strategies. Frédérique Magdinier is invited by Pascal Maire. Plus d'infos...
Nicolas Reynoird is invited by Frédéric Pendino. Plus d'infos...
Tags: Dauphin, Grenoble
Annonce publiée le 19-03-2024
Institut Cochin
Salle Rosalind Franklin
Jeudi 12 Septembre 2024    13:30
Objectifs pédagogiques de la formation
- Connaître les définitions légales des violences sexistes et sexuelles - Connaître les principales données chiffrées sur le sujet - Comprendre les conséquences des violences sexistes et sexuelles - Connaître les responsabilités et obligations de l’employeur, les sanctions encourues et les procédures - Savoir accueillir la parole et orienter
Invite par: Laura Cantini The Targeted Technological Action on Artificial Intelligence (ATC-IA) is organizing the second edition of its Symposium Artificial Intelligence in Biology and Health. It will be held on 4th October 2024 in the Emile ... Plus d'infos...
Tags: IA, Artificial intelligence
Annonce publiée le 04-03-2024
Institut Pasteur
Batiment: Emile Duclaux Salle: Lecture Hall
Mardi 15 Octobre 2024    11:30
Over the past two decades, there has been a significant shift in our understanding of the role of endocytosis and trafficking of signaling receptors. It has evolved from being viewed simply as a signal extinguisher (resulting in long-term attenuation) to being recognized as a sophisticated mechanism capable of delivering signals to specific cellular locations with precise timing. Therefore, endocytosis functions as a regulatory program that impacts various aspects of cell physiology, and we have evidence suggesting that alterations in this program may be causal and targetable in cancer. On the one hand, by exploiting the EGFR model system, we obtained confirmation that the integration of the two functions of endocytosis (sustainment and attenuation of signals) might be achieved, at least in part, at the plasma membrane (PM) by activation of different endocytic routes. Disruption of this balance appears to contribute significantly to cancer cell proliferation, invasion, and metastasis. On the other hand, our research has demonstrated the causal role of an endocytic protein, Epsin3 (EPN3), in breast cancer development, particularly in association with the emergence of partial epithelial-to-mesenchymal transition (pEMT), cancer stem cells, and invasive phenotypes. Increased E-cadherin endocytosis is the initial event driving EPN3-induced pEMT, that render cells more plastic and prone to metastatic dissemination. Importantly, inhibition of increased E-Cadherin endocytosis is capable of reversing EPN3-dependent invasiveness. The restricted expression of EPN3 in adult tissues, along with its overexpression in breast cancer, positions EPN3-drived endocytosis as a promising target for therapeutic intervention.