For the 8th session of the seminar, we are hosting Amira Kramdi and Houda Djerir from the Diversity and Plasticity of Childhood Tumours Team (U830). MYCN and ALK oncogenes are major drivers of neuroblastoma oncogenesis. Our project aims at deciphering how MYCN overexpression and Alk mutation impact the homeostasis of the sympathetic nervous system in NB mouse models. To characterize the adrenal gland, sympathetic ganglia and early stages of tumorigenesis in TH-MYCN/AlkF1178L mice, we used spatial transcriptomics for FFPE (Visium, 10X) combined with single-cell (Chromium, 10X), histology analysis and immunochemistry. In this seminar, we will present some of our preliminary results and address the challenges we face when analysing spatial transcriptomics data for FFPE.
This will be the last session of the Spatial Transcriptomics Odyssey seminar before the summer break. It will also be the opportunity to give some feedbacks on the seminar and on how you would like to make it evolve for next year! The seminar will take place physically at Institut Curie Paris. We encourage you to come onsite to have an interactive discussion. Visioconférence is made available.
Centre de recherche - Paris - Amphitheatre Marie Curie
Mercredi 14 Juin 2023    9:30
How a single embryonic cell interprets its genome to give rise to the many diverse cell types that build an animal is one of nature’s enduring mysteries. Unravelling it promises to not only yield new insights into disorders of development and cancer, but also reveal the organizing principles of life. The genes that drive development each typically have many different enhancers. Properly coordinating the action of these different enhancers is crucial to correctly specifying cell-fate decisions, yet it remains poorly understood how their activity is choregraphed in time. To shed light on this question, we used recently developed single-cell live imaging tools to dissect the regulation of Fushi tarazu (Ftz) in Drosophila melanogaster embryos. Ftz is a transcription factor that is expressed in asymmetric stripes by two distinct enhancers: autoregulatory and zebra. The anterior edge of each stripe needs to be sharply defined to specify essential lineage boundaries. We carefully tracked how boundary cells commit to either a high-Ftz or low-Ftz fate by measuring Ftz protein traces in real time and simultaneously quantifying transcription from the endogenous locus and individual enhancers. This revealed that the autoregulatory enhancer does not establish this fate choice. Instead, it perpetuates the decision defined by zebra. This is contrary to the prevailing view that autoregulation drives the fate decision by causing bi-stable Ftz expression. Furthermore, we showed that the autoregulatory enhancer is not activated based on a Ftz-concentration threshold but through a timing-based mechanism. We hypothesize that this is regulated by several ubiquitously expressed pioneer-like transcription factors, which have recently been shown to act as timers in the embryo. Our work provides new insight into how precisely timed enhancer activity can directly regulate the dynamics of gene regulatory networks, which may be a general mechanism for ensuring that embryogenesis runs like clockwork.
Centre de recherche - Paris - Amphitheatre Marie Curie
Mercredi 14 Juin 2023    11:00
The range of vaccines developed against SARS-CoV-2 gave a unique opportunity to study immunization across different platforms. In a single-center cohort with more than 400 volunteers, we analysed the humoral and cellular immune compartments following five COVID-19 vaccines spanning three technologies (adenoviral, mRNA, and inactivated-virus) administered in 16 combinations. Quantification of specific IgG and IgA anti-spike together with the evaluation of the neutralizing activity of the sera, measurement of spike-specific IFNϒ production, and single cell proteomic analysis of spike-binding memory B cells allowed us to determine four clearly distinct immune signatures elicited by the different vaccine combinations. Our data indicate that the immune response is shaped by the type of vaccines applied and by the order in which they are delivered. Our data provide a framework for improving future vaccines strategies against pathogens and cancer.
Centre de recherche - Paris - Amphitheatre Constant-Burg - 12 rue Lhomond, Paris 5e
Mercredi 14 Juin 2023    11:30
Les interférons de type I (IFN) activent les programmes antimicrobiens intracellulaires et influencent le développement des réponses immunitaires innées et adaptatives. Nous discuterons de nos résultats en abordant la biologie des IFN dans le syndrome de Down (DS). Ce syndrome est la conséquence d'une anomalie chromosomique appelée " trisomie 21 " dans laquelle le chromosome 21 est partiellement ou totalement triplé. Les sous-unités qui composent le récepteur de l'IFN-I (IFNAR1 et IFNAR2), comme d'autres gènes importants pour l'immunologie, sont codés sur ce chromosome et leur expression est fortement augmentée. Cela génère une importante dysrégulation immunologique. Nous discuterons des caractéristiques du compartiment des cellules T, de la fonctionnalité des Tregs, et de l'impact de la signalisation IFN sur les différents sous-ensembles de cellules T, qui pourraient expliquer les différentes susceptibilités de cette population à développer certaines pathologies telles que les tumeurs solides et l'auto-immunité. D'autre part, la signalisation compétente de l'IFN de type I est à la base de la plupart des mécanismes immunitaires anti-tumoraux et s'est récemment avérée essentielle à l'efficacité de plusieurs agents anticancéreux et de l'immunothérapie. Dans cet exposé, nous discuterons de nos récentes découvertes concernant le potentiel des agonistes TLR en tant qu'inducteurs de l'IFN de type I et, par conséquent, en tant que modulateurs puissants de la composition de l'infiltrat tumoral, capables de faire basculer l'environnement tumoral immunosuppressif vers une immunité anti-tumorale.
Invite par: Rogerio Amino Professor Rita TEWARI School of Life Sciences - University of Nottingham Nottingham UK Divide and Rule : Unique biology of cell division in Plasmodium jeudi 15 juin 2023, 12h00 Salle Retrovirus - RDC ... Plus d'infos...
Tags: Malaria, Plasmodium, Rita Tewari, Parasitism, Infectious diseases, Medical specialties, Branches of biology
Invited by Nicolas Minc, Rut Carballido-Lopez will present an IJM seminar on the theme: Actin-like MreB proteins: from single molecules to cell morphogenesis Abstract: How cells control their shape is a long-standing question in cell biology. In bacteria, the external peptidoglycan cell wall -one of the most prominent targets for antibiotics- is the primary determinant of cell shape. Many rod-shaped bacteria elongate their sidewalls by the action of cell wall synthesizing machineries that are associated to circumferentially-moving nanofilaments of MreB, the structural homolog of eukaryotic actin. The prevailing model is that actin-like MreB assemblies are used as platforms that restrict the diffusion and orient the motion of peptidoglycan-synthesizing enzymes in the membrane, thereby patterning new cell wall insertion and controlling cylindrical expansion. We use cutting-edge fluorescence microscopy techniques combined with automated single particle and single molecule tracking to monitor the dynamics of MreB isoforms, as a proxy for cell wall synthesis, in live cells of the model Gram-positive bacterium Bacillus subtilis. We also use super-resolution techniques to elucidate the nanostructure and orientation of MreB cortical assemblies in the cell. In parallel, we are using biochemical and single filament imaging approaches to investigate the polymerization properties of recombinant MreB of B. subtilis in vitro, to fill in the gap between structure and cellular function. Based on our results, we have recently proposed a model for the mechanism of MreB polymerization, which displays some actin-like and some unexpected actin-unlike properties. Plus d'infos...
In the majority of species studied thus far, chromosomes are organized into topologically associated domains (TADs). TAD formation depends on between cohesin, a member of the structural maintenance of chromosome (SMC) complexes family, and boundary sequence elements recognized by transcription factors. TADs are highly conserved across different cell types or species in syntenic regions and are crucial for regulating transcription by restricting the search space of enhancers for target promoters. However, in nematodes, TADs have not been detected in chromosome conformation studies, except on the dosage compensated X chromosomes.
To understand how the nematode genome is folded and how this folding regulates gene expression, we systematically assessed the function of each SMC complex using an inducible cleavage system – cohesin, condensin I and condensin II. Surprisingly, we found that in nematodes, cohesin is functionally replaced by condensin I for long-range chromatin looping. Additionally, we discovered an X-specific looping compartment that aggregates X-specific TAD boundaries, which resembles phase-separated superenhancers described in mammalian cells. This raised the question of the function of cohesins in C. elegans.
The pentameric cohesin complex plays two roles in mammals: sister chromatid cohesion during mitosis and chromatin looping during interphase. In nematodes, these two functions are split between two cohesin isoforms that differ by a single subunit. Our study found that the interphasic cohesin complex is crucial for the formation of 3D hairpin structures that extend from previously characterized enhancer sequences by 10-50 kb, structures which were previously named fountains or jets. Fountains are specific to active enhancers, accumulate the major interphasic cohesin, and disappear when the latter is cleaved in vivo. Additionally, fountains accumulate topological constraints, bind topoisomerases and the negatively supercoiled DNA binder psoralen. Functionally, the disappearance of fountains correlates with active enhancer-proximal gene activation and changes in splicing isoforms for more than 120 genes. Together, this suggests that fountains play a similar role to TADs in directing enhancer-promoter interactions, highlighting an alternative role for cohesin in the regulation of gene expression.
Centre de recherche - Paris - Amphitheatre Marie Curie
Mardi 20 Juin 2023    11:00
Dr. Artyomov will present his work in immune aging where his laboratory using characterized immune aging in mouse tissues identifying GZMK+ CD8 T cells as uniform hallmark of aging. In parallel effort profiling of human circulating immune cells revealed existence of dedicated GZMK+ CD8 effector memory T cells in the peripheral blood that accumulate with age. We will discuss their transcriptional regulation and potential biological implications.
Invite par: David Hardy If you are interested by new technology in Multiplexing in Immunofluorescence on your Histology samples, feel free to come to the COMET (Lunaphore) seminar the 21st June 2023 at 10h45 in the Auditorium Fernbach. ... Plus d'infos...
Tags: Broadcast engineering, Digital radio, Digital television, Multiplexing, Comet, Aircraft, Television, Terminology
The physical organization of bacterial chromosomes is inherently variable, with large conformational fluctuations both from cell to cell and over time. Yet, chromosomes must also be structured to facilitate processes such as transcription, replication, and segregation. A physical description of this dynamic statistical folding of bacterial chromosomes remains largely elusive. In this talk, I will present a fully data-driven maximum entropy approach we developed to extract single-cell 3D chromosome conformations from Hi-C experiments on the model organism Caulobacter crescentus. The predictive power of our model is validated by independent experiments. On large genomic scales, organizational features are predominantly present along the long cell axis: chromosomal loci exhibit striking long-ranged two-point axial correlations, indicating emergent order. This organization is associated with large genomic clusters we term Super Domains (SuDs), whose existence we support with super-resolution microscopy. On smaller genomic scales, our model reveals chromosome extensions that correlate with transcriptional and loop extrusion activity. Finally, I will discuss preliminary results to generalize our data-driven theoretical approach to describe the dynamic statistical organization of chromosomes that are undergoing replication and segregation.
salle Rosalind Franklin, etage 2, 22 rue Mechain 75014
Jeudi 22 Juin 2023    11:00
Invite par: Jean-Louis Mergny Apart from the double-helix B-DNA structure discovered by Watson and Crick, approximately 13% of the human genome comprises sequence motifs that can form non-canonical, or non-B, DNA conformations.
Recent in vivo experiments showed that non-B DNA forms in living cells and regulates key cellular processes (e.g., replication and transcription). This presentation will focus on our recent research related to non-B DNA. Based on the analysis of long-read sequencing data, we demonstrated decreased polymerization speed and increased polymerization errors at non-B DNA loci genome-wide. We next hypothesized that the same phenomena occur in human cells and lead to increased mutagenesis at non-B DNA loci. Indeed, analyzing human diversity and human-orangutan divergence data, we found that non-B DNA are indeed hotspots of mutagenesis and contribute substantially to local and global regional variation in mutation rates across the human genome. Furthermore, we discovered that G-quadruplex motifs, capable of forming one type of non-
B DNA, evolve under purifying selection, are more stable, and are overrepresented when located in different important genic (e.g., promoters) and non-genic (e.g., enhancers and replication origins) regions. Thus, Gquadruplex structures forming in such regions are likely to be functional. In contrast, G-quadruplex motifs do not evolve under selection, are less stable, and are underrepresented when located in the non-transcribed strands of exons. Finally, we showed that caution should be exercised when studying non-B DNA motifs because they exhibit elevated rates of sequencing errors. Tags: Genomics, Molecular biology, DNA, Genetic mapping, Biotechnology, Human genome, G-quadruplex, Gene, Mutagenesis, Mutation
Invite par: MICROB'UP and The Niedergang Lab Pyroptosis is a necrotic form of cell death that was initially found to be induced upon activation of inflammatory caspases by inflammasome complexes. Inflammasomes are cytosolic signaling complexes that are assembled by pattern recognition receptors in response to infection, damage or noxious insults. Mechanistically, pyroptosis induction requires cleavage of the caspase substrate gasdermin D (GSDMD), and the release of the GSDMD N-terminal fragment, which targets the plasma membrane to form large -barrel pores. While induction of cell death has been assumed to be the main function of the gasdermin pores, increasing evidence suggests that these pores have non-lytic functions, such as releasing cytokines or alarmins and regulating intracellular signaling via ionic fluxes. Recently, it was also found that GSDMD-induced cell lysis is an active process requiring plasma membrane disruption by the protein ninjurin-1 (NINJ1). Here we will discuss new insights into the regulation of pyroptosis and the mechanism of NINJ1-driven cell lysis. Plus d'infos...
Tags: Programmed cell death, Microbiology, Immunology, Pyroptosis, Inflammasome, Cell death
Methylation of the mRNA 5’ cap by methyltransferases enables efficient translation and avoids recognition by innate immune factors. We analyze SARS-CoV-2 lacking its 2’-O-methyltransferases Nsp16. We identified a dual role for the 2’-O-methyltransferase Nsp16 during SARS–CoV-2 replication in avoiding efficient recognition by the RNA sensor MDA5 and in shielding its RNA from interferon-induced antiviral responses, thereby identifying Nsp16 as potential candidate for therapeutic intervention.
Mobile genetic elements have significantly shaped our genomic landscape. LINE-1 retroelements are the only autonomously active elements left in the human genome and new insertions can have detrimental consequences. We demonstrate that the antiviral restriction factor TRIM5? senses and blocks LINE-1 retroelements. Thomas Gramberg is invited by Florence Margottin-Goguet. Plus d'infos...
Centre de recherche - Paris - Amphitheatre Marie Curie
Vendredi 23 Juin 2023    11:00
Cell identities are largely defined by their transcriptomes, which result from precise gene activation and silencing programs. In this context, a major and still unresolved question is how particular genes are targeted for repression in certain cell types while they are expressed in others. Here, I will discuss how classic and emerging model species (Drosophila, mice and crickets) deal with this central issue, highlighting common trends but also divergent features, putting into perspective the conservation of these mechanisms.
Tags: Branches of biology, Bacteriology, Microbiology, Organisms, Bacteria, Environmental microbiology, Drosophila, Microbiota, Human gastrointestinal microbiota, Riken, Drosophila quinaria species group, Microbiome in the Drosophila gut
Centre de recherche - Paris - Amphitheatre Constant-Burg - 12 rue Lhomond, Paris 5e
Lundi 26 Juin 2023    11:00
Probing living systems with light-responsive molecules has unlocked new perspectives on the study of biological targets, but also on clinical diagnostics and targeted therapies. However, further progress in opto-biology requires a level of precision that standard, non-specific photo-activation cannot provide. The challenge therefore lies in the development of a toolbox of light-activated probes able to trigger biological responses with high specificity and spatial resolution. This can be achieved either by designing chromophore conjugates modified with biologically-specific ligands, thus providing intrinsic targeting capabilities, or by synthesizing novel chromophores sensitive to multi-photon excitation, in which the excitation is confined to a femtolitre-sized volume.
Here, our latest advances on the design and application of probes for precision diagnostics and therapy will be presented. The synthesis of peptide-chromophore conjugates led to applications in “point-of-care”, target-specific fluorescent diagnosis of infectious diseases, and antimicrobial photodynamic therapy. Further developments on multi-photon-responsive drug-delivery systems, able to elicit spatially controlled pharmacological activity under near-infrared light, will also be discussed. These two complementary molecular engineering strategies hold potential solutions to the healthcare challenges of the next decades, from early-stage diagnostics to multi-drug resistance and targeted cancer treatment.
Centre de recherche - Orsay - Amphitheatre du Batiment 111
Lundi 26 Juin 2023    11:30
Using small molecules to modulate RNA stability is an emerging paradigm which holds promise to greatly expand the space of druggable biomolecules. In this talk I will present two divergent applications of small molecule-induced targeted RNA degradation. Firstly, we devised a click chemistry- and degradation-based method to map RNA modifications, meCLICK-Seq. This unorthodox approach enabled discovery of widespread methylation in low-abundance RNA species, greatly expanding the map of the known methylome. In the second application, we harnessed the degradation strategy to develop small molecules which bind and degrade targeted RNAs. We thus rationally designed anti-SARS-CoV-2 agents which compromise its genomic RNA, exerting an anti-viral effect in cellular and mouse models of SARS-CoV-2 infection. Altogether, these novel RNA manipulation methods enable new, diverse applications, both for basic research and development of therapeutics.
Centre de recherche - Orsay - Amphitheatre du Batiment 111
Lundi 26 Juin 2023    12:00
DNA and RNA containing runs of 3 or 4 adjacent guanines may spontaneously arrange into four-stranded DNA supramolecular structures called G-quadruplexes (G4). These non-canonical structures are likely to form in G-rich regions throughout the genome and thus are assumed to have functional roles in key biological processes, such as replication, transcription, repair, and recombination, and thereby they represent potential barriers for the enzymatic machineries involved in these processes. However, the dynamic nature of these structures makes their identification in live cells extremely challenging; therefore, G4 actual formation in vivo is still a matter of debate. G4 can be stabilized by small synthetic molecules (G4 ligands), hence, the latter represent a new family of DNA / RNA drugs assumed to act region selectively at specific genomic G-rich loci. In general, G4 ligands do not display acute cytotoxicity and produce diverse cellular effects, suggesting that targeting of genomic G4 is characterized by different accessibility. Consequently, it is highly important to follow G4 ligand distribution in cells and identify precisely their binding sites genome- and transcriptome-wide; this knowledge will enhance understanding in regard to characterization and exploitation of drug responses.
Evénement organisée par Dr Etienne Brain et Dr Elisabeth Lucchi, avec le soutien de la Direction de l’Enseignement, ce séminaire aura lieu le 30 juin 2023, à partir de 09h00, en format présentiel, au sein de l’Institut Curie, site de Saint-Cloud (Salle Bourdin, 35 rue Dailly, 92210)
Centre de recherche - Paris - Amphitheatre Marie Curie
Vendredi 30 Juin 2023    14:00
Type I interferons (IFNs) activate intracellular antimicrobial programmes and influence the development of innate and adaptive immune responses. We will discuss our results by addressing the biology of IFN in Down syndrome (DS). This syndrome is the consequence of a chromosomal anomaly known as "trisomy 21" in which chromosome 21 is partially or totally tripled. The subunits that make up the IFN-I receptor (IFNAR1 and IFNAR2), like other genes of immunological relevance, are encoded on this chromosome and their expression is severely increased. This generates an important immunological dysregulation. We will discuss the features of the T cell compartment, Tregs functionality, and the impact of IFN signalling on the different T cell subsets, that could explain the different susceptibilities of this population to develop some pathologies such as solid tumors and autoimmunity. On the other hand, competent type I IFN signalling underlies most anti-tumor immune mechanisms and has recently proven critical to the efficacy of several anticancer agents and immunotherapy. In this talk, we will discuss our recent findings regarding the potential of TLR agonists as type I-IFN inducers and consequently, as strong modulators of the tumor infiltrate composition, capable of switching the immune suppressive tumor environment to anti-tumor immunity.
Centre de recherche - Paris - Amphitheatre Constant-Burg - 12 rue Lhomond, Paris 5e
Lundi 03 Juillet 2023    11:30
Dr. Cheryl Lyn Walker directs the Center for Precision Environmental Health at Baylor College of Medicine, where she holds the Alkek Presidential Chair in Environmental Health. Her research focuses on the epigenetic machinery responsible for “reading, writing and erasing” histone modifications, and the newly discovered role for this machinery outside the nucleus, where it acts directly on the cytoskeleton to regulate the function of microtubules and actin filaments. Several histone methyltransferases, including SETD2 and NSD3 add methyl marks to key lysine residues of microtubules on the mitotic spindle and neuronal cytoskeleton. Chromatin remodeling proteins that recognize histone PTMs also “read” these methyl marks on microtubules, including PBRM1 of the pBAF SWI/SNF complex. In the case of methyl marks on the mitotic spindle, both the SETD2 “writer” and the PBRM1 “reader” are required for genomic stability. In addition to studying how defects in this machinery drive cancer via perturbation of both chromatin and cytoskeletal functions, her group is also elucidating cell signaling pathways and post-translational modifications that alter the activity of these dual-function chromatin and cytoskeleton remodelers. Dr. Walker is the recipient of an R35 Outstanding Investigator Award from the NCI and is a member of the National Academy of Medicine.
Centre de recherche - Orsay - Amphitheatre du Batiment 111
Lundi 03 Juillet 2023    13:30
Invite par: Melanie Bernardini Ridel Biology and medicine are generating vast amounts of data, from DNA sequencing to imaging, that scream for computational analyses. Over the past decade, artificial intelligence (AI) methods such as deep learning have fueled breakthroughs ... Plus d'infos...
Animals from cockroaches to baboons in the wild instinctively mix a healthy, balanced diet. Why can’t we? In this lecture I describe my 35-year research journey with colleague David Raubenheimer to discover the answers to this question. Our scientific detective story involves (among other things) a mediaeval woodland in Oxford, biblical African swarms, cannibal Mormons crickets, a new explanation for the human obesity epidemic, the gift of a Picasso painting, and the establishment of a cathedral to multidisciplinary research in Australia. We show that mixing a nutritionally balanced diet relies on a small number of nutrient-specific appetites, which are universal across the animal kingdom. We discover that we too have these appetites, but they have been hijacked in the modern industrialized food environment, causing the epidemics of obesity and the serious diseases that come with it. We need to listen to our appetites and to place them in a whole-food environment where they can guide us towards a healthy balanced diet - without the need for apps or diet fads.
Intestinal epithelial cells (IECs) are highly polarized and can perform vectorial transport of nutrients using asymmetrically localized membrane proteins and via polarized endocytic and trafficking processes. Using cell biological, forward and reverse genetics, and physiology approaches, we have been investigating mechanisms regulating cell polarization and protein absorption in zebrafish and mice. I will share recent results revealing posttranscriptional mechanisms regulating apical polarization and ongoing studies on how the interaction between diet, microbes, and lysosome rich enterocytes regulates protein absorption.
au College de France - Salle D2
11 place Marcelin Berthelot - 75005 Paris
Mardi 11 Juillet 2023    11:30
Melanoma initiate at the epidermis and become metastatic once invade into the dermis. We present mutation independent trigger of melanoma switch into the invasive dermal phenotype from the radial dermal growth. We further showed how melanoma cells shape the tumor microenvironment by the trafficking of miRNA via large extracellular vesicles. In recent work we found melanoma interactions with the skin immune system in a way that blocks thier activity and promote cancer progression.
Invited by Sandra Duharcourt, Peter Sarkies (Department of Biochemistry, University of Oxford) will give an IJM Seminar entitled: Using evolution to understand epigenetic mechanisms Epigenetics and Evolution Epigenetics allows different types of cells in the body to turn different sets of genes on or off without changing the underlying DNA sequence. epimutations could lead to differences between individuals and therefore drive evolutionary changes. & https://psarkies.wixsite.com/epievo Plus d'infos...
Vendredi 15 Septembre 2023    11:30
I will present two discoveries from my team dealing with precision medicine approaches and possibilities. The first part deals with widely used genotoxic cancer therapy, such as irradiation. These modalities operate through extensive induction of DNA breaks, yet cancer cells frequently display resistance to such interventions. Intriguingly, studies following the dynamics of radiation-induced DNA lesions have identified a temporally distinct and unexplained secondary wave of DNA breaks. Here, I will present our findings on a new pathway that allows tolerance to genotoxic stress. We uncovered that cancer cells actively and reversibly elevate levels of DNA breaks, a mechanism that acts to strengthen the G2/M cell cycle checkpoint thereby limiting premature re-entry into the cell cycle. I will explain the mechanisms underlying this response, which is distinct for cancer cells. Collectively, our findings highlight an unanticipated discovery in cancer biology, demonstrating that tumor cells deploy regulated DNA breaks as a mechanism to delimit the detrimental effects of exogenous DNA double-strand breakage and ensure survival. Finally, in the second part of my presentation I will outline our new approach to determine the phenotypic impact of genetic variants including their impact on drug responses. We call our approach CRISPR-Select, which allows for precise, quantitative, and rapid analysis without the need for generation of clones or selection. It provides unique opportunities for example to identify cancer-causing or drug-response predicting mutations.
Séminaire proposé par Marine Poupon, Chargée de communication
The diversity across tumors from different patients and even across cancer cells from the same patient makes the picture very complex. The idea of ‘personalized’ or ‘precision’ medicine has been suggested, aiming to find tailored treatment regimen for each patient according to the individual genetic background and tumor molecular profile. This attempt is achievable thanks to sufficient molecular characterization of cancers accumulated using high-throughput technologies and advanced imaging technologies. However, despite availability of cancer multi-scale data, they are not fully exploited to provide the clue on deregulated mechanisms that would guide better patients stratification and to specific treatment in cancer.
Hematopoietic stem cells (HSCs) are the rare cells responsible for the lifelong curative effects of hematopoietic cell transplantation. The demand for clinical-grade HSCs has increased significantly in recent decades, leading to major difficulties in treating patients. A promising but not yet achieved goal is the generation of HSCs from pluripotent stem cells. Here, we have obtained vector- and stroma-free transplantable HSCs by differentiating human induced pluripotent stem cells (hiPSCs) using an original one-step culture system. After injection into immunocompromised mice, cells derived from hiPSCs settle in the bone marrow and form a robust multilineage, hematopoietic population that can be serially transplanted. Single cell RNA sequencing shows that this repopulating activity is due to a hematopoietic population that is transcriptionally similar to human embryonic aorta-derived HSCs. Overall, our results demonstrate the generation of HSCs from hiPSC and will help identify key regulators of HSC production during human ontogeny. Thierry Jaffredo is invited by Pascal Maire. Plus d'infos...
Christine Goffinet is a Prof., leader of the team "Innate Immunity and Viral Evasion" at the Institute of Virology from the Berlin Institute of Health. She is since many years an expert in the HIV-1 field, and now also intensively working on SARS-CoV-2, interested in gaining a better understanding of the interplay between host cells and viruses at the cellular and molecular level. She is invited by Serge Benichou. Plus d'infos...
Invite par: Yannick Allanore, Julie Chaumeil, Molly Ingersoll, Catherine Postic, Carina Prip-buus, Dominique Zeliszewski Many recent works demonstrate that biological sex - or whether it is female or male - as well as the number of sex chromosomes carried by an individual, can have a profound impact on various aspects of biology, in homeostasis and in many diseases. The influence of biological sex is still poorly understood and too often ignored both in basic research practices and by the medical profession. The French High Council for Equality between Women and Men noted, in its 2020 report, the importance of taking sex and gender into account to provide better care, as a public health issue.
The Institut Cochin symposium Why sex matters in health and disease will highlight the impact of sex on gene regulation, cancer, immunology and metabolism. In these areas, both the physiological mechanisms involved and the development of chronic diseases such as cancer, autoimmune diseases, diabetes, chronic liver diseases will be addressed. Plus d'infos...
amphitheatre Luton, UFR de Medecine site Cochin, 24 rue du Fg St Jacques 75014
Jeudi 07 Decembre 2023    12:00
Cell plasticity plays an essential role in chronic pancreatitis, human pancreatic cancer (PDAC) and development of diabetes. The morphological processes are closely related to molecular programs known from early embryonic development of the pancreas. Based on these analogies, we have developed new disease models to decipher the causes of the aforementioned pathophysiologies and to design innovative, personalized therapies. One of the core areas in the lab is pancreatic differentiation of human pluripotent stem cells (hPSC). Here , we have differentiated hPSCs into pancreatic duct-like organoids (PDLOs) with morphological, transcriptional, proteomic, and functional characteristics of human pancreatic ducts, further maturing upon transplantation into mice. This model enabled in vitro and in vivo studies of pancreatic plasticity, dysplasia, and cancer formation from a genetically defined background. Using similar models, we also approached the endocrine lineage and revealed that loss of ONECUT1 impairs pancreatic progenitor formation and a subsequent endocrine program. Loss of ONECUT1 altered transcription factor binding and enhancer activity and NKX2.2/NKX6.1 expression in pancreatic progenitor cells. Collectively, we demonstrate that ONECUT1 controls a transcriptional and epigenetic machinery regulating endocrine development, involved in a spectrum of diabetes, encompassing monogenic (recessive and dominant) as well as multifactorial inheritance. In this seminar, I will summarize these seminal papers and give an overview about our unpublished efforts to model pancreatic disorders. Invited by Cécile Julier Plus d'infos...