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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 |
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| Institut Cochin Salle Rosalind Franklin |
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Neuro/evo/devo in Japan and Paris Meeting regarding the latest research on development, evolution and neurobiology using as model organisms birds, fishes, butterflies and Drosophila Organised by Virginie Courtier(contact) Program 10:30: Welcome coffee 11:00 – 11:05: Introduction (V. COURTIER-ORGOGOZO) 11:05 – 11:25: A key pleiotropic gene underlying the diversification of seasonal reproduction in sticklebacks (Asano ISHIKAWA) 11:25 – 11:45: Developmental bases of trends and variation in color patterns (Marie MANCEAU) 11:45 – 12:05: Drosophila pigmentation: a model to study the impact of environmental and natural genetic variations and the role of developmental constraints (Jean-Michel GIBERT) 12:05 – 14:00: Lunch 14:00 – 14:20: Evolution of Drosophila glue (Virginie COURTIER-ORGOGOZO) 14:20 – 14:40: How Fish Stay Upright: Neural Mechanisms of Head Tilt Sensing and Balance Control in Zebrafish (Masashi TANIMOTO) 14:40 – 15:00: From ecology to neural adaptation in flower-visiting Drosophila elegans (Yuki ISHIKAWA) 15:00 – 15:20: From ecological divergence to genetic architecture: what is driving sympatric speciation? (Violaine LLAURENS) 15:20: End of the meeting Abstracts (alphabetical order of names) Evolution of Drosophila glue Virginie COURTIER-ORGOGOZO At the end of the larval stage, Drosophila larvae produce a proteinaceous glue that allows the animal to adhere to a substrate for several days during metamorphosis. We are currently using Drosophila powerful genetic tools to identify the genes involved in glue adhesion and understand how they have changed during evolution so that the glue can stick to various substrates in diverse environments. We developed a new assay to quantify Drosophila glue adhesiveness and compared adhesion between different Drosophila melanogaster populations and Drosophila species. We identified one particular Drosophila species with highly adhesive glue. Furthermore, we also explore natural environments (rotten fruits, soil, etc.) to understand better this fascinating biomaterial that is Drosophila glue. Our ultimate goal is not only to better understand adaptation but also to develop new bioadhesives inspired from Drosophila glue. Drosophila pigmentation: a model to study the impact of environmental and natural genetic variations and the role of developmental constraints Jean-Michel GIBERT Drosophila pigmentation is involved in many adaptive process such as thermoregulation or protection against UV, parasites or pathogens. Furthermore, in Drosophila melanogaster pigmentation is genetically variable and modulated by temperature during development. Using female abdominal pigmentation as a model, we analyzed the genetic bases of these phenomenon. We found that temperature modulates the expression of regulatory and effector genes involved in pigmentation, and, interestingly, that these genes carry variation modulating pigmentation in natural populations. In addition, we showed that a particular pigmentation pattern on the thorax is linked to developmental constraints, as it is shaped by flight muscle attachment sites. A key pleiotropic gene underlying the diversification of seasonal reproduction in sticklebacks Asano ISHIKAWA Reproductive timing is a key life-history trait that affects fitness, with populations often undergoing diversification in reproductive patterns to adapt to varying seasonal environments. However, the molecular genetic mechanisms underlying differences in reproductive seasonality are not well understood. To address this, we use the three-spined stickleback (Gasterosteus aculeatus) as a model. While marine ecotypes of sticklebacks reproduce in early summer, freshwater ecotypes show significant variation in reproductive timing, with stream ecotypes at lower latitudes breeding almost year-round. Our study reveals that marine sticklebacks exhibit a photoperiodic response in gonad development, while this response is lost in stream ecotypes, which evolved independently in Japan and North America. Transcriptome analysis identified the thyroid stimulating hormone beta 2 (TSH?2) gene as a key regulator of this response. Knocking out TSH?2 in marine ecotypes led to earlier maturation under short photoperiods, similar to stream ecotypes in terms of behavior, body size, hormone levels, and brain transcriptome. Linkage mapping revealed that the loss of seasonality in stream ecotypes is due to convergent mutations in the TSH?2 pathway-cis-regulatory in North America and trans-regulatory in Japan. Single-cell analysis detected a novel TSH?2-expressing 2 pituitary cell cluster, and we observed increased TSH?2 expression and chromatin accessibility under short-day conditions. These findings suggest that transcriptional and epigenetic mechanisms drive the evolution of reproductive seasonality in sticklebacks. From ecology to neural adaptation in flower-visiting Drosophila elegans Yuki ISHIKAWA Flower-visiting behavior in insects is essential for plant reproduction and the stability of terrestrial ecosystems. Although insects have existed on Earth long before the evolution of flowering plants, they developed flower-visiting behavior in parallel with the adaptive radiation of angiosperms. However, the neural basis of this behavioral evolution remains unclear. To investigate this, we studied Drosophila elegans, a flower-breeding species closely related to the non-flower-visiting model organism D. melanogaster. D. elegans has evolved a flower-dependent life cycle and exhibits pronounced flower-visiting behavior in its natural habitat. Field observations revealed that it relies on specific flower species for both breeding and feeding. These ecological preferences suggest behavioral and neural adaptations that enable recognition of appropriate flowers. Behavioral assays showed that visual cues-especially color-are crucial for flower recognition. Comparative analyses suggest that its visual system is adapted to detect relevant flower colors, and genome editing identified specific photoreceptor cells that are essential for this behavior. In this talk, I will discuss how ecological specialization and neural adaptation have together contributed to the evolution of flower-visiting behavior in this species. From ecological divergence to genetic architecture: what is driving sympatric speciation? Violaine LLAURENS Determining the evolutionary forces initiating and fuelling the speciation process is challenging, especially when population divergence occurs in sympatry. Sympatric speciation often involves complex interactions between ecological specialization generating divergent selection and the accumulation of genetic barriers to gene flow. Here we focus on a pair of sister-species of butterflies (M. achilles and M. helenor) observed in sympatry throughout the Amazonian basin, and sharing similar micro-habitat but diverging in the timing of male patrolling behaviour. Since M. helenor has a larger geographical range, we compared the temporal niche in sympatric and allopatric populations of this species and found a significant shift in patrolling hours, suggesting that the evolution of temporal niches might contribute to the speciation or reinforcement process. Using population genomics, we then reconstructed the history of speciation between these two species and investigated the heterogeneity in the level of genetic divergence throughout the genome. We found a very strong differentiation in the sexual chromosome (Z) as compared to the autosomes between species but not between populations within species. We then specifically tested for the effect of selection in such increased rate of evolution in the Z chromosomes and found significantly higher signals of positive selection in the Z vs. the autosomes in sympatric population, while such a signal was missing in the allopatric ones. Furthermore, by testing the association between the temporal niche and genomic variations across populations of M. helenor, we found significant signals on two loci within the Z-chromosome, including one non-coding region located between the circadian genes PDP1 and Period. Altogether, our results raise questions on the implication of the Z chromosome in ecological specialization and speciation in sympatry. Developmental bases of trends and variation in color patterns Marie MANCEAU The color patterns that adorn animals' coats exhibit extensive diversity linked to various ecological functions, but also display recurrences in geometry, orientation or body location. How processes of pattern formation shape such phenotypic trends remains a mystery. We surveyed plumage color patterns in poultry birds and passerine finches respectively displaying variation in striped pattern and color domain distribution, and identified conserved features that we linked to embryonic pre-patterns (i.e. putative embryonic skin regions outlined by the combinatory expression of few genetic markers). We showed that these pre-patterns are instructed by early developmental tissues, variation resulting from late dose-dependent mechanisms controlling stripe width, or pigmentation choices that mask or display skin domains. This work revealed that early conserved landmarks and molecular pathways are a major cause of phenotypic trends. How Fish Stay Upright: Neural Mechanisms of Head Tilt Sensing and Balance Control in Zebrafish Masashi TANIMOTO Body equilibrium is vital for all living organisms. In vertebrates, vestibular signals from the inner ear play pivotal roles in maintaining balance. Larval zebrafish serve as an advantageous model since their transparent tissues facilitate live imaging of neural mechanisms during behavior. We developed an imaging system that simultaneously visualizes neural activity and behavior while controlling fish orientation. Using this approach, we revealed the neural mechanisms of head tilt sensing and posture control. I will share what fish study can tell us about vertebrate balance control.
Plus d'infos...
Tags: Ecology, Evolutionary biology, Speciation, Animal models, Biogeography, Drosophila, Sympatric speciation, Allopatric speciation, Three-spined stickleback, Reinforcement, Ecotype, Evolution
Annonce publiée le 22-07-2025
Institut Jacques Monod
Institut Jacques Monod Salle Francois Jacob, 15 rue Helene Brion, Paris, France -
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.
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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