A5038408248- Advanced Electron Microscopy Techniques and Applications
- Hippo pathway signaling and YAP/TAZ
- Toxoplasma gondii Research Studies
- Autophagy in Disease and Therapy
- Nuclear Structure and Function
- Microtubule and mitosis dynamics
- interferon and immune responses
- Cellular transport and secretion
- Hepatitis Viruses Studies and Epidemiology
- T-cell and B-cell Immunology
- Metabolism and Genetic Disorders
- Advanced Fluorescence Microscopy Techniques
- Phagocytosis and Immune Regulation
- Neurological and metabolic disorders
- Cellular Mechanics and Interactions
- RNA Research and Splicing
- Electron and X-Ray Spectroscopy Techniques
- Supramolecular Self-Assembly in Materials
- Lipid Membrane Structure and Behavior
- Inflammasome and immune disorders
- Hepatitis C virus research
- Characterization and Applications of Magnetic Nanoparticles
- Electrolyte and hormonal disorders
- Calcium signaling and nucleotide metabolism
- Ubiquitin and proteasome pathways
The Francis Crick Institute
2015-2024
Inserm
2005-2017
Nantes Université
2017
Centre National de la Recherche Scientifique
2017
The Honourable Society of Lincoln's Inn
2012-2015
Cancer Research UK
2012-2014
Université Paris-Saclay
2005-2011
Université Paris Cité
2011
Assistance Publique – Hôpitaux de Paris
2009-2011
Krankenhaus Salem
2011
Autophagosome formation requires sequential translocation of autophagy-specific proteins to membranes enriched in PI3P and connected the ER. Preceding this, earliest structure forming de novo is a small punctum ULK1 complex. The provenance this its mode are unknown. We show that emerges from regions, where ATG9 vesicles align with ER exit coatomer function. Super-resolution microscopy reveals compartment consists regularly assembled punctate elements cluster progressively larger spherical...
Cancer metastasis depends on cell survival following loss of extracellular matrix attachment and dissemination through the circulation. The metastatic spread can be enhanced by clustering detached cancer cells increased antioxidant defense. Here, we link these responses describing how limits reactive oxygen species (ROS). Loss causes mitochondrial perturbations ROS production. formation clusters induces a hypoxic environment that drives hypoxia-inducible factor 1-alpha (Hif1α)-mediated...
Additional studies are required to identify risk factors for hepatitis C virus (HCV) transmission health care workers after occupational exposure HCV.We conducted a matched case-control study in 5 European countries from 1 January 1991 through 31 December 2002. Case patients were who experienced seroconversion percutaneous or mucocutaneous HCV. Control subjects HCV-exposed did not experience and with case center period of exposure.Sixty 204 control included the study. All exposed...
Fluorescence microscopy of GFP-tagged proteins is a fundamental tool in cell biology, but without seeing the structure surrounding cellular space, functional information can be lost. Here we present protocol that preserves GFP and mCherry fluorescence mammalian cells embedded resin with electron contrast to reveal ultrastructure. Ultrathin in-resin (IRF) sections were imaged simultaneously for signals an integrated light scanning microscope. We show, first time, stable active vacuo. applied...
The processes of life take place in multiple dimensions, but imaging these even three dimensions is challenging. Here we describe a workflow for 3D correlative light and electron microscopy (CLEM) cell monolayers using fluorescence to identify follow biological events, combined with serial blockface scanning analyse the underlying ultrastructure. encompasses all steps from culture sample processing, strategy image processing/analysis. We demonstrate successful application studies, each...
Autophagy is important in a variety of cellular and pathophysiological situations; however, its role immune responses remains elusive. Here, we show that among B cells, germinal center (GC) cells exhibited the highest rate autophagy during viral infection. In contrast to mechanistic target rapamycin complex 1-dependent canonical autophagy, GC cell occurred predominantly through noncanonical pathway. stimulation was sufficient down-regulate transiently while triggering autophagy. Genetic...
Somatic mutations commonly occur in hematopoietic stem cells (HSCs). Some mutant clones outgrow through clonal hematopoiesis (CH) and produce mutated immune progenies shaping host immunity. Individuals with CH are asymptomatic but have an increased risk of developing leukemia, cardiovascular pulmonary inflammatory diseases, severe infections. Using genetic engineering human HSCs (hHSCs) transplantation immunodeficient mice, we describe how a gene CH, TET2, affects neutrophil development...
Metastasis involves dissemination of cancer cells away from a primary tumour and colonization at distal sites. During this process, the mechanical properties nucleus must be tuned since they pose challenge to negotiation physical constraints imposed by microenvironment tissue structure. We discovered increased expression inner nuclear membrane protein LAP1 in metastatic melanoma cells, invasive front human tumours metastases. Human express two isoforms (LAP1B LAP1C), which differ their amino...
Entosis is a form of epithelial cell cannibalism that prevalent in human cancer, typically triggered by loss matrix adhesion. Here, we report an alternative mechanism for entosis cells, driven mitosis. Mitotic regulated Cdc42, which controls mitotic morphology. Cdc42 depletion enhances deadhesion and rounding, these biophysical changes, depend on RhoA activation are phenocopied Rap1 inhibition, permit subsequent entosis. occurs constitutively some cancer lines index correlates with primary...
The small Rho GTPase Cdc42, known to interact with Wiskott–Aldrich syndrome (WAS) protein, is an important regulator of actin remodeling. Here, we show that genetic ablation Cdc42 exclusively in the B cell lineage sufficient render mice unable mount antibody responses. Indeed Cdc42-deficient are incapable forming germinal centers or generating plasma cells upon either viral infection immunization. Such severe immune deficiency caused by multiple and profound abnormalities, including early...
Vascularization is driven by morphogen signals and mechanical cues that coordinately regulate cellular force generation, migration, shape change to sculpt the developing vascular network. However, it remains unclear whether vasculature actively regulates its own properties achieve effective vascularization. We engineered tissue constructs containing endothelial cells fibroblasts investigate mechanics of Tissue stiffness increases during morphogenesis resulting from emergent interactions...
The functions and morphology of cellular membranes are intimately related depend not only on their protein content but also the repertoire lipids that comprise them. In absence in vivo data lipid asymmetry endomembranes, it has been argued motors, scaffolding proteins or integral membrane rather than non-lamellar bilayer such as diacylglycerol (DAG), responsible for shaping organelles, local curvature fusion. effects direct alteration levels remain predominantly uninvestigated....
Super-resolution light microscopy, correlative and electron volume microscopy are revolutionising the way in which biological samples examined understood. Here, we combine these approaches to deliver super-accurate correlation of fluorescent proteins cellular structures. We show that YFP GFP have enhanced blinking properties when embedded acrylic resin imaged under partial vacuum, enabling vacuo single molecule localisation microscopy. In conventional section-based experiments, specimen must...
Abstract YAP1 gene fusions have been observed in a subset of paediatric ependymomas. Here we show that, ectopic expression active nuclear (nlsYAP5SA) ventricular zone neural progenitor cells using conditionally-induced NEX/NeuroD6-Cre is sufficient to drive brain tumour formation mice. Neuronal differentiation inhibited the hippocampus. Deletion YAP1’s negative regulators LATS1 and LATS2 kinases NEX-Cre lineage double conditional knockout mice also generates similar tumours, which are...
Hematopoietic progenitor kinase 1 (HPK1) is implicated in signaling downstream of the T cell receptor. Its non-catalytic, C-terminal half contains several prolinerich motifs, which have been shown to interact with different SH3 domain-containing adaptor proteins vitro. One these, Mona/Gads, was also bind HPK1 mouse cells vivo. The region that binds Mona/Gads domain has mapped and shows only very limited similarity a recently identified high affinity binding motif SLP-76, another T-cell...
Metazoan cell death mechanisms are diverse and include numerous non-apoptotic programs. One program called entosis involves the invasion of live cells into their neighbors is known to occur in cancers. Here, we identify a developmental function for entosis: clear male-specific linker C. elegans. The leads migration shape gonad removed facilitate fusion cloaca. We find that cleared manner involving cell-cell adhesions cell-autonomous control uptake through actin. Linker generates lobe...
ABSTRACT A variable (GT) n repeat in the 5′‐regulatory region of N ‐methyl‐D‐aspartate GRIN2A subtype has recently been identified and associated with psychiatric disorders. In this study, we examined association polymorphism alcohol dependence. Subject–control analysis included 206 alcohol‐dependent 168 control subjects. Average observed numbers genotype distributions were significantly different ( P ‐value = 0.001) subjects versus Short alleles less frequent among (odds ratio 0.58, 7 × 10...
1 The pharmacokinetics of atenolol, after 200 mg orally, were studied in 18 patients with terminal renal insufficiency (creatinine clearance less than 5 ml/min), whom twelve being treated by chronic dialysis. 2 peak plasma level, 1.59 +/- 0.43 mg/l, was reached 4.7 2.1 h. 3 Without dialysis treatment, the apparent half-life atenolol greatly increased (73.4 28.8 /). During dialysis, it dropped to 7.5 3.7 h but returned 51.2 17.3 plot a rising slope for few hours end 4 Renal very low (4.6 1.5...