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Jeudi 03 Juillet 2025    10:00
Animals have evolved in a microbial world and must coexist with dense, multispecies microbial communities. We use gnotobiotic zebrafish to understand the molecular exchanges that maintain homeostasis between resident bacteria and their hosts. We have identified several secreted bacterial proteins that impact animal development and tissue homeostasis. Our biochemical and cell biological analyses of these proteins reveal that their primary functions are in bacterial competition within the host environment. Our findings that these bacterial proteins have additional impacts on host cell biology reveal how animal developmental programs have incorporated adaptations to microbial cues that shape developmental trajectories and physiologies. Selected publications: -Smith, T Jarrod et al. A mucin-regulated adhesin determines the spatial organization and inflammatory character of a bacterial symbiont in the vertebrate gut.? Cell host & microbe(2023) -Hill, Jennifer Hampton et al. BefA, a microbiota-secreted membrane disrupter, disseminates to the pancreas and increases ? cell mass.?Cell metabolism(2022) -Robinson, Catherine D et al. Host-emitted amino acid cues regulate bacterial chemokinesis to enhance colonization.? Cell host & microbe(2021) -Troll, Joshua V et al. Microbiota promote secretory cell determination in the intestinal epithelium by modulating host Notch signaling.? Development(2018) -Hill, Jennifer Hampton et al. A conserved bacterial protein induces pancreatic beta cell expansion during zebrafish development.? eLife (2016) Plus d'infos...
Centre de recherche - Paris - Amphitheatre Helene Martel-Massignac (BDD)
Jeudi 03 Juillet 2025    12:00
Recent advances in technologyparticularly in the field of single-cell and spatial omicshave greatly improved our understanding of fibroblast differentiation into extracellular matrixsecreting myofibroblasts. These approaches have revealed previously unrecognized intermediate states within the fibroblast lineage. Among them, a distinct inflammatory fibroblast subset has emerged, characterized by its ability to recruit macrophages and contribute to the initiation and expansion of the fibrogenic niche.In this seminar, I will present the identification and characterization of these inflammatory fibroblasts, and discuss their functional role in the development and progression of kidney fibrosis. Plus d'infos...
Tags: Membrane biology, Lipid bilayer, Lamellar phase, Model lipid bilayer
Annonce publiée le 24-05-2025
Institut Curie
Centre de recherche - Paris - Amphitheatre Marie Curie
Vendredi 04 Juillet 2025    12:00
Invite par: Mario Pende David M. Sabatini studies nutrient sensing and growth control, particularly by the mechanistic Target of Rapamycin (mTOR) pathway. This pathway is the major nutrient-sensitive growth regulator in animals and plays a central role in physiology, metabolism, aging, and cancer. Sabatini discovered the mTOR protein kinase, and most other components of the pathway, including the mTOR-containing complexes mTORC1 and mTORC2, and established them as growth regulators in cells and in vivo. He determined that nutrients signal to mTORC1 through the lysosome-associated Rag GTPases and discovered their many regulators and associated nutrient sensors. In addition to his growth-related work, Sabatini also studies small molecule metabolism and is involved in technology development, such as in generating widely used genome-scale RNAi and CRISPR/Cas9 libraries as well as organellar isolation methods.
Sabatini was born in New York City to Argentine immigrant parents and obtained his bacheloramp; Prague and was previously at MIT.Seminar topic: Nutrient sensing by the mTOR pathwayImage Copyright: Tomas Bellon Plus d'infos...
Tags: Protein complexes, Signal transduction, MTOR, David M. Sabatini, Nutrient sensing, Sirolimus, MTOR inhibitors, Ragulator-Rag complex
Centre de recherche - Paris - Amphitheatre Marie Curie
Vendredi 04 Juillet 2025    17:00
The neocortex is essential for all cognitive functions, facilitated by the complex interplay of neuronal networks formed through synaptic interactions among various neuron types. In this context, inhibitory interneurons play a critical role in coordinating cortical activity. These inhibitory circuits are regulated by a variety of neuromodulators, with acetylcholine standing out for its significant control over cortical dynamics. Cholinergic signalling is central to the modulation of neuronal circuits and underpins key cognitive functions such as attention, learning, memory, perception, and motivation. Plus d'infos...
Centre de recherche - Paris - Amphitheatre Marie Curie
Mardi 08 Juillet 2025    9:30
During embryogenesis, precise spatial-temporal patterns from transcription factors (TFs) establish the body plan of the embryo. These TFs function as master regulatory switches controlling genes that instruct cells to adopt specific morphologies and functions to form different organs, tissues, and body segments. For example, TFs from the Homeobox (Hox) family specify the identity of individual body segments along the anterior-posterior axis. However, developmental genes targeted by Hox TFs such as shavenbaby (svb), which terminally fates cells in the ectoderm into trichomes, have enhancers controlled exclusively by low affinity binding sites for the Hox factor Ultrabithorax (Ubx). Moreover, live imaging experiments tracking TF binding in multicellular eukaryotes suggest that TF-DNA interactions are in general short-lived, lasting on average for only a few seconds. Given this stochastic and low-affinity molecular foundation, how can TFs drive efficient gene expression leading to robust phenotype development on the embryo? My work using high- and super-resolution fluorescence microscopy in Drosophila melanogaster embryos showed that svb transcription sites reside in nuclear regions enriched for Ubx. These local environments are co-enriched for specific transcriptional cofactors, thus preserving both regulatory specificity and transcriptional efficiency. Epigenetic modifications, such as H3K4me1, also play an important role in preserving the integrity of these transcriptional microenvironments and regulatory specificity. Finally, genes co-regulated by the same TF can share and reinforce these transcriptional hubs, improving the robustness of gene expression and of phenotype development when embryos are subjected to environmental and genetic stresses. Thus, understanding how the nuclear organization of TFs evolves during embryo development to form and maintain specialized transcriptional hubs, as well as how they can organize stochastic and transient molecular interactions into precise and robust regulatory signals will help decipher how multicellular eukaryotes physically organize their nuclei to shape gene expression. Plus d'infos...
Centre de recherche - Paris - Amphitheatre Marie Curie
Mardi 08 Juillet 2025    11:45
Invitee par l’equipe Wassmann, Professor Adele L. Marston (Centre for Cell Biology, University of Edinburgh) presentera un seminaire de l’Institut Jacques Monod sur le theme : Functional organisation of pericentromeres in mitosis and meiosis Resume : Our overall goal is to understand how cells inherit the correct number of chromosomes during mitosis and meiosis. Deviations in chromosome number, called aneuploidy, are a hallmark of cancer and cause birth defects, miscarriages and infertility. Mitosis generates genetically identical daughter cells by evenly segregating the sister chromatids. Meiosis partitions half the genome into gametes through two consecutive segregation events: homologs segregate in meiosis-I, followed by sister chromatids in meiosis-II. Meiosis is especially error-prone: around 1% of human sperm and up to 30% of oocytes are aneuploid. To discover molecular mechanisms, we exploit the tractability of yeast, combined with work in frog, mouse and human oocytes. Our approach is guided by the research question, leading to the employment and development of a wide range of cell biological, genomic, proteomic and biochemical assays. Our group discovered unanticipated roles for pericentromeres, discrete chromosomal domains flanking centromeres, and specialised functions for kinetochores in orienting chromosomes to ensure accurate segregation. In my seminar I will discuss our recent work revealing how pericentromere organization directs accurate chromosome segregation in mitosis and meiosis, in both yeast and oocytes. Plus d'infos...
Tags: Cell cycle, Chromosomes, Cellular processes, DNA replication, In science, Meiosis, Chromosome segregation, Mitosis, Kinetochore, Cell division, Centromere, Sister chromatids
Annonce publiée le 04-06-2025
Institut Jacques Monod
Institut Jacques Monod Salle Francois Jacob, 15 rue Helene Brion, Paris, France
Vendredi 11 Juillet 2025    11:45
Le 11 juillet, Gijsje Koenderink (Department of Bionanoscience, Kavli Institute of Nanoscience Delft, Delft University of Technology) presentera une conference de l’Institut Jacques Monod sur le theme : How cytoskeletal crosstalk makes cells strong Resume : Our bodies are built up of cells and tissues with unique physical properties. Cells and tissues are dynamic but also need to withstand large mechanical loads. This paradoxical mechanical behavior is governed by fibrous protein scaffolds known as the cytoskeleton and the extracellular matrix. Fibrous networks have many advantageous mechanical properties: fibers can form space-filling elastic networks at low volume fractions and they reversibly stress-stiffen, which provides protection from damage. However, it is still poorly understood how biopolymer networks can combine these features with the ability to dynamically adapt their structure and mechanics. In this seminar I will focus on the cytoskeleton: how can the cytoskeleton combine mechanical strength with the ability to dynamically adapt its structure and mechanics? I will summarize our recent insights in this question obtained via quantitative measurements on living cells coupled with experiments on cell-free model systems. I will focus on the role of mechanical crosstalk between the actin, intermediate filament, and septin cytoskeletal networkds, three key determinants of cell mechanics. These three filamentous systems contribute different structural and dynamical properties, but their activities are closely coordinated. I will show that combining cell and cell-free assays allows us to dissect the collaborative and individual roles of the cytoskeletal systems. Our findings may eventually be interesting to guide the search for selective anticancer drugs, since cancer cells often overexpress specific intermediate filaments or septins leading to abnormal mechanical behaviors. Plus d'infos...
Institut Jacques Monod Amphitheatre Buffon, 15 rue Helene Brion, Paris, France
Mercredi 16 Juillet 2025    11:00
Trypanosoma cruzi, the causative agent of Chagas disease, remains a major public health challenge with no effective vaccine. Understanding how dendritic cells (DCs) orchestrate T cell responses is critical to developing new immunotherapeutic strategies. Using a conditional knockout mouse model (Sec22b ? / ? in DCs), we demonstrate that cross-presentation is essential for protective CD8 ? T cell responses againstT. cruzi. Sec22b-deficient mice exhibit increased parasitemia, reduced survival, and impaired CD8 ? T cell priming. We performed immunopeptidomics on DCs exposed to infected cells or dead parasites, identifying ~20T. cruzi-derived MHC I peptides per condition, including known antigens like trans-sialidases and flagellin. Vaccination with peptide-pulsed, Poly(I:C)-stimulated BMDCs or with peptide-antibody conjugates targeting Clec9a ? DCs led to robust T cell responses and partial protection in vivo. Together, these findings support the critical role of cross-presentation inT. cruziimmunity and highlight the potential of DC-targeted vaccines for Chagas disease. Plus d'infos...
Centre de recherche - Paris - Amphitheatre Helene Martel-Massignac (BDD)
Mardi 26 Aout 2025    0:00
Vijay KUCHROO's research mainly focuses on the regulation of T cell responses in the context of autoimmune disease, to elucidate the role of cytokines and transcription factors in the differentiation of CD4+ T helper subsets and the role of co-stimulatory and co-inhibitory receptors and their ligands in the regulation of autoreactive T cell responses.
The team identified Tim-3 on CD4 + Th1 cells, leading to the discovery of the TIM molecule family. Tim-3 is now recognized as an important co-inhibitory receptor that dampens T cell responses in chronic viral diseases and cancer. Other key discoveries made in his lab include the elucidation of the differentiation factors for Th17, Th9 and Tr1 cells, all of which have a major influence on the development of autoimmunity and tissue inflammation. Vijay Kuchroo is invited by Armelle Blondel. Plus d'infos...
Tags: Immunology, Immune system, T cells, HAVCR2, Vijay Kuchroo, T helper 17 cell, Regulatory B cell, Immune checkpoint
Annonce publiée le 23-05-2025
Institut Cochin
Salle Rosalind Franklin
Jeudi 11 Septembre 2025    0:00
Clear cell renal cell carcinoma (ccRCC) is a prevalent and aggressive subtype of kidney cancer. Immunotherapies that boost the ability of CD8+ T cells to eliminate cancer cells have become a standard of care for ccRCC. However, tumor infiltration of CD8+ T cells can result in contradicting clinical outcomes, potentially due to the functional heterogeneity among tumor-specific CD8+ T cells. In this study, we observed that ccRCC tumors are infiltrated by circulating (Tcirc) and tissue-resident (Trm) memory CD8+ T cells that specifically recognize autologous RCC cells in an HLA class I-dependent manner. Trm cells exhibited higher tumor reactivity but reduced stemness potential and a more exhausted state, whereas Tcirc cells retained higher stemness and cytotoxic potential. Single-cell transcriptomics revealed a rather heterogenous composition of memory populations, including cytotoxic and progenitor Tcirc subsets, as well as multiple Trm subsets, including exhausted Trm cells. TCR and trajectory analyses indicate that circulating progenitors lose their circulation, cytotoxicity and stemness potential within the tumor microenvironment while progressively acquiring a tissue-resident differentiation program followed by a terminal differentiation state. Interestingly, tumor enrichment of Trm and cytotoxic Tcirc cells predicts better survival, while exhausted Trm and total CD8+ T cells predict worse survival in RCC patients. Our findings provide new insights into the differentiation pathways and clinical impact of tumor-specific memory CD8+ T cells infiltrating human RCC tumors. Adoptive T cell therapy (ACT) has demonstrated remarkable efficacy in treating hematological cancers. However, its efficacy against solid tumors remains limited and the emergence of cancer cells that lose expression of targeted antigens promotes resistance to ACT. The mechanisms underlying effective and durable ACT-mediated tumor control are incompletely understood. Here, we show that adoptive transfer of TCR-transgenic CD8+ T cells that efficiently eliminates established murine tumors induces tumor accumulation of CD8+ T cells exhibiting tumor-reactive phenotypes. Interestingly, host CD8+ T cells contributed to ACT-mediated elimination of primary tumors and rejected ACT-resistant melanoma cells lacking the targeted antigen. Mechanistically, ACT induced TNF-?- and dendritic cell-dependent tumor accumulation of endogenous CD8+ T cells and effective tumor elimination. Importantly, although lymphodepleting preconditioning enhanced expansion of transferred cells and ACT-mediated tumor elimination, it impaired host antitumor immunity and abrogated protection against ACT-resistant tumors. Tumor enrichment of transcriptional signatures associated with TNF-? signaling, cross-presenting dendritic cells and tumor-specific CD8+ T cells in correlated with favorable responses to ACT and increased survival in human cancers. Our findings reveal that long-term efficacy of ACT is determined by the interplay between transferred and endogenous CD8+ T cells and is undermined by lymphodepleting preconditioning, which ultimately favors ACT resistance. Plus d'infos...
Analyse de donnees multimodales et modelisation de reseaux pour maitriser les capacites distinctives des cancers Le cours reunira des intervenants de premier plan issus de differents domaines de la biologie des systemes cancereux, de la recherche sur le cancer et de la clinique. Les orateurs invites exposeront diverses approches pour l analyse et l interpretation des donnees omiques, d imagerie et cliniques, en combinant les reseaux de signalisation avec des donnees moleculaires multi-echelles, et en les associant a des donnees cliniques. Les themes abordes comprennent l integration et l analyse de donnees genomiques multimodales, les algorithmes de prediction de la sensibilite aux medicaments, l identification de biomarqueurs et de facteurs de cancer, la stratification des patients, et les applications de la modelisation mathematique et de l analyse d images dans le domaine du cancer. Cette edition comprendra egalement de nouvelles sessions consacrees aux applications actuelles du traitement du langage naturel dans la biologie des systemes computationnels du cancer, a l integration des donnees epigenomiques, ainsi qu aux approches de pharmacologie systemique et de metabolomique. Enfin, un moment fort de la rencontre sera la celebration du 25e anniversaire de la publication de l article fondamental "The hallmarks of cancer" (les capacites distinctives des cancers) de Hanahan et Weinberg (Cell 2000). Plus d'infos...
Annonce publiée le 18-03-2025
Institut Curie
Centre de recherche - Paris - Amphitheatre Helene Martel-Massignac (BDD)
L'un des enjeux fondamentaux de la biologie est la comprehension de la relation entre les multiples echelles spatiales et temporelles observees dans un systeme biologique. Des molecules a une fonction cellulaire, d'une collection de cellules a un organisme, ou d'individus a une population, les interactions complexes entre elements singuliers peuvent donner naissance a des proprietes «emergentes» au niveau de l'ensemble. Dans quelle mesure l'ordre spatial et temporel vu au niveau du systeme peut-il etre explique par des proprietes de sous-echelle?ObjectifsCet enseignement a pour objectif de presenter les outils physiques qui ont ete recemment developpes pour decrire cette integration d'echelle (le matin) et de les mettre en application sur des exemples biologiques dans le cadre de seminaires (l'apres-midi). Plus d'infos...
Annonce publiée le 12-06-2025
Institut Curie
Centre de recherche - Paris - Amphitheatre Marie Curie
Vendredi 05 Decembre 2025    11:00