To display seminars of one specific institute, first press 'None' and then the institute of interest.
Monday 13 May 2024    11:00
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.
Hopital site de Paris - Amphitheatre Constant-Burg - 12 rue Lhomond, Paris 5e
Wednesday 03 April 2024    11:30
The spatial organization and dynamics of the cytoskeleton play crucial roles for various cellular functions. However, despite their essential roles in processes such as cell migration, mechanical stress resilience, and maintaining cellular integrity, the complex nature of vimentin intermediate filament networks continues to elude our understanding. Unlike actin and microtubules, recreating physiological vimentin networks in vitro has posed significant challenges. Using a cell extract-based approach, we reconstituted vimentin networks outside cells and investigated the factors influencing their architecture. Moreover, given that vimentin lacks inherent dynamics and relies on microtubule-associated molecular motors for its intracellular distribution, we explored direct interactions between vimentin and microtubules in vitro. In sum, we offer insights into the formation of complex vimentin networks and shed light on their interplay with microtubules.
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.
Centre de recherche - Paris - Amphitheatre Constant-Burg - 12 rue Lhomond, Paris 5e
Wednesday 03 April 2024    9:30
Despite the well-established role of nuclear organization in the regulation of gene expression, little is known about the reverse: how transcription shapes the spatial organization of the genome. In particular, given the relatively small sizes of genes and the limited resolution of light microscopy, the structure and spatial arrangement of a single transcribed gene are poorly understood.
We made use of several long highly expressed mammalian genes and demonstrated that they form Transcription Loops with polymerases moving along the loops and carrying nascent RNAs that undergo co-transcriptional splicing. This finding rules out a popular hypothesis about eukaryotic transcription occurring in so called Transcription Factories with immobilized polymerases and genes reeling through them.
Transcription loops dynamically modify their harboring loci and extend into the nuclear interior suggesting an intrinsic stiffness of these structures. Both experimental evidence and polymer modeling support the hypothesis that transcription loop stiffness results from the dense decoration of transcribed genes with multiple voluminous nascent RNPs.
We propose that transcription loop formation is the universal principle of eukaryotic gene expression, which has not been appreciated until now due to the limitation of light microscopy resolution and due to the small size or low expression of studied genes.
Centre de recherche - Paris - Amphitheatre Constant-Burg - 12 rue Lhomond, Paris 5e
Friday 03 May 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.
Centre de recherche - Paris - Amphitheatre Constant-Burg - 12 rue Lhomond, Paris 5e
Friday 12 April 2024    11:30
Towards a comprehensive single-cell picture of RNA isoforms in mouse and human brain and their diseases
Most mammalian genes encode multiple distinct RNA isoforms and the brain harbors especially diverse isoforms. Complex tissue includes diverse cell types, which employ distinct isoforms. To untangle cell-type specific brain isoform profiles, we developed the first single-cell long-read technology for >>1,000 cells and fresh tissues (Single-cell isoform RNA sequencing - ScISOr-Seq [1]) as well as for frozen tissues (Single-nuclei isoform RNA sequencing - SnISOr-Seq [2]). To add spatial resolution, we developed Slide-isoform sequencing (Sl-ISO-Seq) [3]. We have mapped single-cell isoform expression across development, brain regions and species for the NIH Brain Initiative, and we have implemented highly accurate long-read interpretation software [4]. Finally, I will comment on further, yet unpublished, technologies of the lab.
Tags: Protein isoform, Protein structure, Clusters of differentiation, Tropomyosin
Published on 22-03-2024
Institut Curie
Centre de recherche - Paris - Amphitheatre Helene Martel-Massignac (BDD)
Wednesday 17 April 2024    11:30
Any imaging technique is limited by lts field of view. As objects or particles move in and out of the observation field, tracking their motion, especially over long periods, beoomes challenging. ln addition, available analysis techniques face challenges reconstructing trajectories in dense and heterogeneous systems where accurately labelling partlcles is difficult. Here, we shift this paradigm by introducing a broadly-applicable technique that probes dynamics simply by counting particles in finite observation boxes. Using colloïdal experiments, simulations, and theory, we demonstrate that statistical properties of fluctuating counts can be used to determine self-diffusion coefficients. Our framework alleviates the hurdles associated with trajectory reconstruction. We subsequently show that by increasing the observation box size, counting naturally enables the study of collective dynamics. We extend our technique to various suspensions, such as ions or active partlcles. The "Countoscope" offers the unique possibility to systematically llnk individual and collective behavior, opening up broad soft matter and statistical physics perspectives.
Centre de recherche - Paris - Amphitheatre Marie Curie
Friday 05 April 2024    12:00
Invited by: Marie-Anne FELIX - Section Ecologie et Biologie de l’Evolution Abstract :
Closely-related species living in sympatry are usually partitioned in different ecological niches but still display multiple common traits due to both shared ancestry and shared selective pressures. Here, we investigate ecological and genomic factors favouring the diversification in different niches and maintaining barriers to gene flow in Morpho butterflies. In this neo-tropical genus, up to nine species can co-exist in sympatry, and occupy different microhabitats from the understory to the canopy of the same Amazonian locality. During this talk, I will first focus on the evolution of divergent timing of reproductive activities among species, and show evidence on the effect of convergent evolution of colour pattern cues on the evolution of allochrony. Then, I will show recent results on the evolution of the sex-chromosomes and their putative role in reproductive isolation. Finally, I will detail the evolution of circadian genes in this genus, focusing in particular on signature of positive selection on the circadian gene Period, located on the sex chromosome Z. Altogether, this talk will highlight the feed-backs between ecological interactions between sympatric species and the evolution of their genomes. More details...
Bogdan Sieriebriennikov1,2, Hua Yan2 and Claude Desplan1
(1) NYU Biology, New York
(2) University of Florida, Gainesville
In both flies and vertebrates, smell is perceived by olfactory sensory neurons (OSNs) that rely on the expression of a single odorant receptor (Or) gene per cell to discriminate between odors. Flies have few Or genes (~60), while mammals have many (>1,000 in mice), which is reflected in different specification mechanisms of developing OSNs in these species. The simple olfactory system of flies uses deterministic specification of cell fates by a transcription factor code, while the complex olfactory system of mammals relies on stochastic choices, including stochastic enhancer-promoter interactions, complemented by negative cross-regulation between Ors. Ants, which extensively rely on smell to navigate their physical and social milieu, lie in the middle of this spectrum. The jumping ant Harpegnathos saltator has an order of magnitude more Or genes than Drosophila melanogaster (~400). The additional genes have evolved via tandem duplications, creating large genomic arrays of Or genes positioned head-to-tail, an arrangement reminiscent of Or arrays in mammals. We investigated the expression pattern of Ors in individual OSNs in H. saltator by performing single-nucleus sequencing on the antennae. Unexpectedly, we observed that all genes in tandem Or arrays are co-expressed in a “stair step” fashion where either the most 3’ gene is expressed alone, or the two most downstream genes are co-expressed, or the last three genes are co-expressed etc. Additionally, the expression levels of multiple co-expressed genes shows a decreasing trend towards the most 3’ transcribed Or, suggesting that such co-expression may result from RNA polymerase readthrough. We propose that a single Or promoter is stochastically chosen from a cluster, activating the transcription of the corresponding gene. However, RNA polymerase fails to terminate at the end of this gene, producing long RNAs. While they include all the downstream Or sequences, those cannot be translated due to their distance from the 5’ cap. At the same time, upstream Or genes are repressed through additional mechanisms which we are currently investigating. Thus, genomic clusters of ant Ors, which have evolved to accommodate an expanded repertoire of odors related to the ants’ lifestyle, may rely on a unique mechanism to produce singular OR protein expression in each OSN.
Tags: Olfactory receptors, Olfactory system, Otorhinolaryngology, Limbic system, Sense of smell, Claude Desplan, Olfaction, Olfactory memory, Olfactory bulb
Published on 18-03-2024
Institut Curie
Centre de recherche - Paris - Amphitheatre Helene Martel-Massignac (BDD)
Wednesday 10 April 2024
Invited by the Ribes Lab, Mustafa Mir (Assistant Professor of Cell and Developmental Biology, University of Pennsylvania, Childrens Hospital of Philadelphia, and Howard Hughes Medical Institute) will present an Institut Jacques Monod Seminar on the theme: Molecular kinetics of gene regulation during embryonic development Abstract: During early development gene expression patterns progressively emerge as cell fates are determined and the embryo takes form. The seminar will take place on Wednesday, April 10th 2024 at 11am in room& Francois Jacob (15 rue Helene Brion) More details...
Tags: Developmental biology, Development of the human body, Animal embryonic development, Embryo
Published on 16-03-2024
Institut Jacques Monod
Usually at 11.45 am in the Francois Jacob room
Thursday 19 September 2024    0:00
Invited by the Konstantinides Lab, Dafni Hadjieconomou (Team leader at the GutSense lab, Paris Brain Institute (ICM)) will present an Institut Jacques Monod Seminars on the theme: Mind the gut a tale of two brains Abstract: A series of tightly controlled processes ensure that energy is either stored or consumed within an organism. This control is central to survival and prosperity of the animal, yet we only partly understand it. Communication between the brain and the gut, the so called brain-gut axis, has emerged as a key player in regulating aspects of animal physiology by directly affecting energy stores. Nevertheless, due to the astonishing anatomical complexity of the underlying neural circuits in mammals, an in depth understanding of the cellular and molecular mechanisms controlling this axis is still lacking. Using the simpler, yet functionally comparable The seminar will take place on Friday, April 19th 2024& a& 11h45 in room Francois Jacob. More details...
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. More details...
Invited by: Romain Levayer This is the first session of our new lunch/minisymposium serie that will gather every 2 months 3 internal + 1 external speaker on a given topic. More details...
Tags: Lunch
Published on 13-03-2024
Institut Pasteur
Batiment: Monod Salle: 03, 7th floor
Wednesday 24 April 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.
Tags: Cell biology, Nuclear transport, Ran, Neurodevelopmental disorder, Development of the nervous system
Published on 09-03-2024
NeuroPSI
Salle de conference Albe-Fessard
Tuesday 21 May 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
Thursday 13 June 2024    0:00
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. More details...
Webinaire proposé dans le cadre de la Journée mondiale de sensibilisation à l’autisme
Savez-vous comment les talents uniques des personnes autistes peuvent transformer le monde professionnel ?
Découvrez les réponses lors de notre conférence de sensibilisation sur l'autisme ! Explorez la diversité et les talents uniques présents dans le spectre autistique.
Ce que vous apprendrez :
- Ce que signifie être porteur d’autisme : Démystifiez les idées préconçues et explorez la richesse de la neurodiversité.
- Les défis auxquelles les personnes autistes sont confrontées dans leur travail en matière de communication, de socialisation et de sensibilité sensorielle.
- Les forces cachées : Découvrez les talents exceptionnels que les personnes autistes apportent à l’organisation et à la société.
- quels besoins, ressources et soutiens : Explorez les solutions pratiques pour créer un environnement de travail inclusif et respectueux. au cœur de notre organisation
A l’occasion de la journée de l’autisme, rejoignez-nous le 2 avril pour une conférence qui changera votre perspective sur le sujet et vous inspirera à accueillir la neurodiversité dans tous les aspects de la vie professionnelle.
Cette conférence sera animée par Laurence Moszkowicz, coach professionnelle certifiée qui accompagne les personnes neuro-atypiques dans l'emploi (Autistes Asperger - Hauts potentiels Intellectuels - Personnes Dys et TDAH).
Elle partagera ses connaissances et expériences, et répondra à toutes vos questions posées dans le chat.
Do you know how the unique talents of people with autism can transform the professional world?
Discover the answers at our Autism Awareness Conference! Explore the diversity and unique talents present in the autism spectrum.
What you'll learn:
- What it means to be a carrier of autism: Demystify preconceptions and explore the richness of neurodiversity.
- The challenges autistic people face in their work in terms of communication, socialization and sensory sensitivity.
- Hidden strengths: Discover the exceptional talents that people with autism bring to the organization and to society.
- What needs, resources, and support? Explore practical solutions for creating an inclusive and respectful work environment. at the heart of our organization
On the occasion of Autism Day, join us on April 2 for a conference that will change your perspective on the subject and inspire you to welcome neurodiversity in all aspects of professional life.
This conference will be hosted by Laurence Moszkowicz, a certified professional coach who accompanies neuro-atypical people in employment (Autistic Asperger's - High Intellectual Potentials - Dys and ADHD people).
She will share her knowledge and experience and answer all your questions in the chat.
Invited by: 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 ... More details...
Tags: IA, Artificial intelligence
Published on 04-03-2024
Institut Pasteur
Batiment: Emile Duclaux Salle: Lecture Hall
Wednesday 03 April 2024    11:30
To function, organisms rely on vital organs which, in turn, rely on specialized cells. At the subcellular scale, cell specialization is notably driven by robust mechanisms of organelle remodeling. Thus, discovering these mechanisms is key for the fundamental understanding of organisms in health and disease, as well as for improved organ engineering. In this seminar, I will discuss my research on organelle remodeling in somatic and female germ cells. I will first show how multiciliated cells - critical for nervous, respiratory and reproductive organs - repurpose conserved mechanisms of cell division to remodel organelles for motile ciliogenesis. I will then talk about how oocytes deploy a biophysical mechanism, based on cytoplasmic force tuning, to mechanically remodel nuclear RNA-processing organelles for reproductive success. I will conclude with some future research plans, blending my past and present interests into an interdisciplinary project that will venture into unexplored grounds of nuclear organelle mechano-regulation in somatic cells to deepen our understanding of organ development and homeostasis.
Key relevant publications :
Al Jord, A. et al. Centriole amplification by mother and daughter centrioles differs in multiciliated cells. Nature 516, 104–107 (2014).
Al Jord, A. et al. Calibrated mitotic oscillator drives motile ciliogenesis. Science 358, 803–806 (2017).
Al Jord, A. et al. Cytoplasmic forces functionally reorganize nuclear condensates in oocytes. Nat. Commun. 13:5070, 1–19 (2022).
au College de France - Amphitheatre G. Bude
11 place Marcelin Berthelot - 75005 Paris
Wednesday 22 May 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.
Centre de recherche - Paris - Amphitheatre Helene Martel-Massignac (BDD)
Thursday 04 July 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. More details...
Tags: Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society, Cell and molecular biology
Published on 29-02-2024
Institut Cochin
Salle Rosalind Franklin
Friday 29 March 2024
Invited by the Ladoux/Mege Lab, Jacopo Di Russo (REMeD lab Interdisciplinary Centre for Clinical Research, RWTH Aachen University and DWI Leibniz-Institute for Interactive Materials) will present an IJM seminar on the theme: Mesoscale Epithelial Mechanobiology and Cellular Interfaces Abstract: Mechanical properties regulate tissue functions at a multicellular length scale or mesoscale. These properties depend on the interaction of cells with their interfaces, hence on the balance between intercellular tension and the extracellular matrix (ECM) adhesion forces. My group aims to dissect the role of cell-ECM and cell-cell communication in epithelial mechanobiology, starting from the medically relevant retinal epithelium. In contrast to the experimental investigation of traditional biological sciences, my laboratory uses cross-disciplinary approaches combining synthetic hydrogels with stem cell-based models. We particularly develop and adapt biohybrid systems where cells interact with hydrogels that are designed to control cell-cell or cell-ECM adhesion. Synthetic material allows the unique reduction of the degree of freedom in the cellular/tissue system, thus helping us to reveal phenotypical tissue plasticity and molecular function. My talk will first give an overview of published work[1],[2] on understanding how ECM physical (elasticity) and biochemical cues (receptor density) impact epithelial system properties, namely stress heterogeneity and intercellular force coordination. I will show that these properties are not only in vitro observations but play pivotal roles in controlling our vision. A density gradient of ECM characterises the contractility of the retinal epithelium in vivo and modulates its efficiency in supporting photoreceptor cells#8217; homeostasis. Furthermore, I will show data from the ongoing work which addresses different aspects of the mechanobiology of tissue ageing. We optimised a phototunable hydrogel as substrates for epithelia to model ECM local remodelling on demand. Moreover, we developed microgels used as phototunable phantom cells to simulate age-related tissue mechanical anisotropy. Altogether, we can dissect the relationship between tissue mechanics and function by controlling the temporal and spatial properties of cellular interfaces. [1]https://doi.org/10.7554/eLife.69861 [2] https://doi.org/10.1101/2023.02.24.529913 The seminar will take place on Friday, March 29th at 11.45 am in room Francois Jacob. More details...
Tags: Extracellular matrix, Mechanobiology
Published on 29-02-2024
Institut Jacques Monod
Usually at 11.45 am in the Francois Jacob room
Friday 29 March 2024    12:00
Invited by: Helene MORLON - Section Ecologie et Biologie de l’Evolution More details...
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.
Centre de recherche - Paris - Amphitheatre Marie Curie
Monday 22 April 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.
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
Published on 16-02-2024
Institut Curie
Centre de recherche - Orsay - Salle polyvalente du Batiment 111
Thursday 04 April 2024    11:30
In this seminar, we will discuss Live-seq, a transformative method for single-cell gene expression profiling that eliminates the need for cell isolation and lysis. Live-seq utilizes Fluidic Force Microscopy (FluidFM) to extract cytosolic picolitre biopsies from living cells, which are subsequently analysed with a highly-sensitive RNA-seq protocol. While the resulting gene expression profiles faithfully represent lysed cell transcriptomes, the sampled cells remain alive and functional in their original microenvironment. Live-seq thus enables spatially-resolved, longitudinal profiling and phenotyping of individual cells, offering exciting opportunities for investigating cellular dynamics and cell-cell communication.
Tags: Olfactory system, Cerebral cortex, Limbic system, Otorhinolaryngology, Piriform cortex, Sense of smell, Piriform, Anterior olfactory nucleus, Rhinencephalon
Published on 08-02-2024
Institut Pasteur
Salle AMPHI DUCLAUX,
Friday 05 April 2024    11:00
Abstract
Meiotic recombination involves repair of double strand DNA breaks by homologous recombination to form crossovers and noncrossovers. Current models suggest that different mechanisms form these two products: noncrossovers by synthesis dependent strand annealing; COs by double Holliday junction formation and resolution. In testing these predictions, we found evidence for remarkable dynamism during meiotic DSB repair. This includes switching between repair templates and strand invasion by both DSB ends during both noncrossover and crossover recombination, and extensive branch migration by the Holliday junction intermediates that are CO precursors. I will discuss the mechanistic and regulatory implications of these findings.
Tags: Cellular processes, Molecular genetics, Postmodern literature, The Garden of Forking Paths, Forking paths problem, Genetic recombination
Published on 08-02-2024
Institut Curie
Centre de recherche - Paris - Amphitheatre Helene Martel-Massignac (BDD)
Monday 22 April 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)
Monday 08 April 2024    0:00
Cet atelier de 3 jours a pour objectif d’expliquer ce qu’est la radiomique, d’en définir les bonnes pratiques et d’enseigner l’utilisation du logiciel gratuit et convivial LIFEx pour analyser les images et réaliser des études radiomiques.
La formation inclura des enseignements magistraux et de nombreux travaux pratiques qui permettront aux participants de se familiariser avec les nombreuses fonctionnalités du logiciel LIFEx. A noter que l’utilisation de LIFEx ne nécessite pas de compétences en programmation.
Chaque participant travaillera sur son propre ordinateur portable, sur des exemples émanant de bases de données d’images publiques. A l’issue de la formation, chaque participant devrait avoir acquis une bonne maîtrise du logiciel lui permettant de réaliser des études radiomiques en autonomie.
Centre de recherche - Paris - Amphitheatre Helene Martel-Massignac (BDD)
Thursday 04 April 2024    16:45
L’évènement, organisé par Dr Laurence Bozec et Dr Chrystelle Colas, aura lieu le 4 avril 2024 à partir de 16h45, en format présentiel, au sein de l’Institut Curie, site de Saint-Cloud (Salle Bourdin, 35 rue Dailly, 92210).
Hopital site de Saint-Cloud - Salle Jacques-Sylvain Bourdin - 3e etage
Thursday 12 September 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
- 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
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. More details...
Published on 22-01-2024
Institut Cochin
Salle Rosalind Franklin
Wednesday 24 April 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 ... More details...
Tags: Scientific method, Formal sciences, Data analysis, Artificial intelligence, Analysis
Published on 20-01-2024
Institut Pasteur
Wednesday 24 April 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 ... More details...
Invited by: Cassandra Koh Keywords: Genome instability, DNA replication, replication stress, centromere, DNA damage More details...
Tags: DNA replication, Chromosomes, Molecular genetics, Cell cycle, DNA replication stress, Centromere, Genome instability, S phase, DNA
Published on 29-12-2023
Institut Pasteur
Batiment JACOB , salle Auditorium Francois JACOB ,
Tuesday 21 May 2024    11:00
Invited by: Cassandra Koh Keywords: drug abuse, neurodevelopment, extracellular vesicles, basic science More details...
Published on 29-12-2023
Institut Pasteur
Batiment JACOB, salle Auditorium Francois JACOB ,
Thursday 30 May 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. More details...
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. More details...
Tags: Cell biology, Senescence, Chromosomal abnormalities, Cytogenetics, Cells, Cellular senescence, Centromere, Inflammaging, Aneuploidy, T cell, Kinetochore, Tim J. Yen
Published on 16-12-2023
Institut Cochin
Salle Rosalind Franklin
Thursday 04 April 2024    0:00
Sickle cell disease (SCD) is due to a mutation in the ?-globin gene causing production of the toxic sickle hemoglobin (HbS; ?2?S2). Transplantation of autologous hematopoietic stem and progenitor cells (HSPCs) transduced with lentiviral vectors (LVs) expressing an anti-sickling ?-globin (?AS) is a promising treatment; however, it is only partially effective, and patients still present elevated HbS levels. Here, we developed a bifunctional LV expressing ?AS3-globin and an artificial microRNA (amiRNA) specifically downregulating ?S-globin expression with the aim of reducing HbS levels and favoring ?AS3 incorporation into Hb tetramers. Efficient transduction of SCD HSPCs by the bifunctional LV led to a substantial decrease of ?S-globin transcripts in HSPC-derived erythroid cells, a significant reduction of HbS+ red cells, and effective correction of the sickling phenotype, outperforming ?AS gene addition and BCL11A gene silencing strategies. The bifunctional LV showed a standard integration profile, and neither HSPC viability, engraftment, and multilineage differentiation nor the erythroid transcriptome and miRNAome were affected by the treatment, confirming the safety of this therapeutic strategy. In conclusion, the combination of gene addition and gene silencing strategies can improve the efficacy of current LV-based therapeutic approaches without increasing the mutagenic vector load, thus representing a novel treatment for SCD. Invited by Suzanne Faure-Dupuy, Alberto De la Iglesia and Hugo Barreto, as part of the Post-doc seminar series. More details...
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. More details...
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.