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Genomic instability induced by uncontrolled binding of RAD51 to chromosomal DNA and a model of RAD51-mediated homology search based on the AF3 prediction Plus d'infos... Tags: DNA repair, RAD51, Double-strand break repair model, BRCA2 Annonce publiée le 04-07-2025 |
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| Institut Curie Centre de recherche - Paris - Amphitheatre Marie Curie |
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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 -
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...
Tags: Immunology, Immune system, T cells, Adoptive cell transfer, Tumor microenvironment, Dendritic cell, Lymphocyte, Immunotherapy, Immunoediting, Natural killer cell
Annonce publiée le 08-07-2025
Institut Curie
Centre de recherche - Paris - Amphitheatre Constant-Burg - 12 rue Lhomond, Paris 5e -
Centromeres orchestrate the accurate partitioning of the genome during cell division, preventing catastrophic segregation errors in dividing cells. It is now clear that centromeric malfunctions contribute to establishing and maintaining cancer, but no compounds targeting centromeric chromatin have been identified using standard drug discovery approaches. Here we developed a large-scale data-mining approached aimed at probing centromeric protein composition and its change in response to small-molecule treatment. We discovered that the bromodomain inhibitor JQ1, which prevents BET proteins from associating with acetylated chromatin, redirects its target protein BRD4 to bind centromeric chromatin. JQ1 achieves this by acting as a non-degrading molecular glue stabilising a direct interaction between the second bromodomain of BRD4 and Centromere Protein B (CENP-B). At the molecular scale, a single atom replacement within the t-butyl ester moiety of JQ1 completely abolishes localisation of BRD4 to the centromere. Strikingly, derivatives of JQ1 that performed poorly in the clinic lack this moiety and centromere-targeting functionality. CENP-B is essential for JQ1-mediated effects on centromere cohesion and mechanisms that render cells resistant to JQ1, revealing a key unexplored avenue for future drug discovery.
Plus d'infos...
Tags: Chromosomes, Protein domains, BET inhibitor, Centromere, JQ1, BRD4, Bromodomain, BRDT, Kinetochore
Annonce publiée le 16-07-2025
Institut Curie
Centre de recherche - Paris - Amphitheatre Marie Curie -
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...
Tags: Immunology, Immune system, T cells, Adoptive cell transfer, Tumor microenvironment, Dendritic cell, Lymphocyte, Immunotherapy, Immunoediting, Natural killer cell
Annonce publiée le 14-03-2025
Institut Cochin
Salle Rosalind Franklin -
Isabelle Meyts is invited by Jérome Delon.
Plus d'infos...
Annonce publiée le 28-06-2025
Institut Cochin
Salle Rosalind Franklin -
Invite par: LEVRAUD Jean-Pierre
Plus d'infos...
Tags: Regenerative biomedicine, Danio, Freshwater fish of India, Stem cell research, Zebrafish, Spinal cord, Neural tube, Floor plate
Annonce publiée le 28-06-2025
NeuroPSI
Salle de conference Albe-Fessard -
Invite par l’equipe Minc, Jan Brugues (Physics of Life Excellence Cluster,TU Dresden ) presentera un seminaire de l’Institut Jacques Monod : Self-organization of the cytoplasm by physical instabilities Resume : Early development across vertebrates and insectscritically relies on robustly reorganizing the cytoplasm of fertilized eggs intoindividualized cells. This intricate process is orchestrated by largemicrotubule structures that traverse the embryo, partitioning thecytoplasminto physically distinct and stable compartments. Despite the robustness ofembryonic development, here we uncoveran intrinsic instability in cytoplasmic partitioningdriven by the microtubule cytoskeleton. We reveal that embryos circumvent thisinstabilitythrough two distinct mechanisms: either by matching the cell cycle duration tothetimeneeded for the instability tounfoldor by limiting microtubule nucleation. These regulatorymechanisms give rise to two possible strategies to fill the cytoplasm,which weexperimentally demonstrate in vitro and in zebrafish andDrosophilaembryos. Ourresults indicate that the temporal control of microtubule dynamics could havedriven the evolutionary emergence of species-specific mechanisms for effectivecytoplasmic organization.Furthermore,our study unveils afundamental synergy betweenphysical instabilities and biological clocks,uncovering universal strategies for rapid, robust, and efficient spatial orderinginbiological systems.
Plus d'infos...
Tags: Cytoskeleton, Microtubule, Cytoplasm, Cell
Annonce publiée le 16-07-2025
Institut Jacques Monod
Institut Jacques Monod Salle Francois Jacob, 15 rue Helene Brion, Paris, France -
Invite par: SHULZ Daniel
Plus d'infos...
Tags: Medical terminology, Neuron, Sensory systems, Neural coding, Perception, Sonja Hofer, Sensory neuroscience
Annonce publiée le 01-07-2025
NeuroPSI
Salle de conference Albe-Fessard -
Plus d'infos...
Annonce publiée le 14-05-2025
Inst. Bio. Paris Seine
7-9 quai Saint Bernard, 75005 Paris -
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).
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Annonce publiée le 18-03-2025
Institut Curie
Centre de recherche - Paris - Amphitheatre Helene Martel-Massignac (BDD) -
Invitation de Sophie Vaulont.
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Annonce publiée le 29-03-2025
Institut Cochin
Salle Rosalind Franklin -
Plus d'infos...
Annonce publiée le 14-05-2025
Inst. Bio. Paris Seine
7-9 quai Saint Bernard, 75005 Paris -
Invite par: VAILLEND Cyrille
Plus d'infos...
Tags: Duchenne, Glucose
Annonce publiée le 01-07-2025
NeuroPSI
Salle de conference Albe-Fessard -
Invite par: PERRON Muriel
Plus d'infos...
Tags: Developmental neuroscience, Cajal, Retzius, Santiago Ramn y Cajal, Gustaf Retzius
Annonce publiée le 01-07-2025
NeuroPSI
Salle de conference Albe-Fessard -
Invited by Julie Cocquet and Alberto de la Iglesia.
Plus d'infos...
Tags: European Molecular Biology Laboratory, Heidelberg
Annonce publiée le 04-04-2025
Institut Cochin
Salle Rosalind Franklin -
Plus d'infos...
Annonce publiée le 14-05-2025
Inst. Bio. Paris Seine
7-9 quai Saint Bernard, 75005 Paris -
Plus d'infos...
Annonce publiée le 11-06-2025
Institut Curie
Centre de recherche - Paris - Amphitheatre Helene Martel-Massignac (BDD) -
Les galaxies ne voguent pas de façon désordonnée dans l’Univers mais forment un véritable réseau en bulles de savon que l’on appelle la toile cosmique. Cette toile est composée de grands vides entourés par des filaments le long desquels les galaxies se meuvent avant de terminer leur course aux noeuds où de gigantesques amas de galaxies se forment. A l'occasion de cette conférence, nous arpenterons l'Univers sur des milliards d'années lumière afin de comprendre comme se tisse cette toile cosmique, quelles sont ses origines, comment elle influence la naissance et l'évolution des galaxies et en quoi elle représente une sonde cosmologique formidable nous permettant de comprendre l'Histoire et la composition de l’Univers.
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Annonce publiée le 03-07-2025
Institut Cochin
Salle Rosalind Franklin -
Invited by Anne Hosmalin.
Plus d'infos...
Tags: Vaccine-preventable diseases, Influenza, Orthomyxoviridae, Live attenuated influenza vaccine, Influenza vaccine
Annonce publiée le 28-06-2025
Institut Cochin
Salle Rosalind Franklin -
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).
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Annonce publiée le 12-06-2025
Institut Curie
Centre de recherche - Paris - Amphitheatre Marie Curie -
Plus d'infos...
Annonce publiée le 14-05-2025
Inst. Bio. Paris Seine
7-9 quai Saint Bernard, 75005 Paris -
Plus d'infos...
Annonce publiée le 14-05-2025
Inst. Bio. Paris Seine
7-9 quai Saint Bernard, 75005 Paris -
Plus d'infos...
Annonce publiée le 14-05-2025
Inst. Bio. Paris Seine
7-9 quai Saint Bernard, 75005 Paris