A5010221188- Genetic and Kidney Cyst Diseases
- Microtubule and mitosis dynamics
- Protist diversity and phylogeny
- Retinal Development and Disorders
- Renal and related cancers
- Retinal Diseases and Treatments
- Retinal and Macular Surgery
- Advanced Electron Microscopy Techniques and Applications
- MicroRNA in disease regulation
- Developmental Biology and Gene Regulation
- Plant Molecular Biology Research
- Lipid metabolism and biosynthesis
- Micro and Nano Robotics
- RNA Research and Splicing
- Advanced Fluorescence Microscopy Techniques
- Force Microscopy Techniques and Applications
- Congenital heart defects research
- Neonatal Respiratory Health Research
- Retinopathy of Prematurity Studies
- Plant Virus Research Studies
- Cellular transport and secretion
- Amino Acid Enzymes and Metabolism
- Cystic Fibrosis Research Advances
- CRISPR and Genetic Engineering
- Cancer-related molecular mechanisms research
University of Geneva
2021-2024
École Normale Supérieure - PSL
2018-2023
Inserm
2018-2019
Centre National de la Recherche Scientifique
2015-2019
Institut de Biologie de l'École Normale Supérieure
2018-2019
Université Paris Sciences et Lettres
2018-2019
Institut de Pharmacologie Moléculaire et Cellulaire
2015-2018
Université Côte d'Azur
2015-2018
Université de Tours
2015
Centre Val de Loire
2015
Expansion microscopy (ExM) is a highly effective technique for super-resolution fluorescence that enables imaging of biological samples beyond the diffraction limit with conventional microscopes. Despite development several enhanced protocols, ExM has not yet demonstrated ability to achieve precision nanoscopy techniques such as Single Molecule Localization Microscopy (SMLM). Here, address this limitation, we have developed an iterative ultrastructure expansion (iU-ExM) approach achieves...
Inherited retinal degeneration due to loss of photoreceptor cells is a leading cause human blindness. These possess photosensitive outer segment linked the cell body through connecting cilium (CC). While structural defects CC have been associated with degeneration, its nanoscale molecular composition, assembly, and function are barely known. Here, using expansion microscopy electron microscopy, we reveal architecture demonstrate that microtubules together by inner scaffold containing POC5,...
Cilia and flagella are specialized eukaryotic organelles projecting from the surface of cells that play a central role in various physiological processes, including cell motility, sensory perception, signal transduction. At base these structures lies ciliary transition zone, pivotal region functions as gatekeeper communication hub for activities. Despite its crucial role, intricacies architecture remain poorly understood, especially given variations organization across different types...
Abstract Multiciliated cells (MCCs) harbor dozens to hundreds of motile cilia, which generate hydrodynamic forces important in animal physiology. In vertebrates, MCC differentiation involves massive centriole production by poorly characterized structures called deuterosomes. Here, single-cell RNA sequencing reveals that human deuterosome stage MCCs are the expression many cell cycle-related genes. We further investigated uncharacterized vertebrate-specific division cycle 20B ( CDC20B ) gene,...
Abstract For 15 years, gene therapy has been viewed as a beacon of hope for inherited retinal diseases. Many preclinical investigations have centered around vectors with maximal expression capabilities, yet despite efficient transfer, minimal physiological improvements observed in various ciliopathies. Retinitis pigmentosa-type 28 (RP28) is the consequence bi-allelic null mutations FAM161A, an essential protein structure photoreceptor connecting cilium (CC). In its absence, cilia become...
Abstract Vertebrate multiciliated cells (MCCs) contribute to fluid propulsion in several biological processes. We previously showed that microRNAs of the miR-34/449 family trigger MCC differentiation by repressing cell cycle genes and Notch pathway. Here, using human Xenopus MCCs, we show beyond this initial step, later promote assembly an apical actin network, required for proper basal bodies anchoring. Identification targets related small GTPase pathways led us characterize R-Ras as a key...
Despite the importance of mucociliary epithelia in animal physiology, mechanisms controlling their establishment are poorly understood. Using developing Xenopus epidermis and regenerating human upper airways, we reveal BMP signalling for construction vertebrate epithelia. In Xenopus, attenuation activity is necessary specification multiciliated cells (MCCs), ionocytes small secretory (SSCs). Conversely, required proper differentiation goblet cells. Our data suggest that Notch pathways...
Leber congenital amaurosis (LCA) is a group of inherited retinal diseases (IRDs) characterized by the early onset and rapid loss photoreceptor cells. Despite discovery growing number genes associated with this disease, molecular mechanisms cell degeneration most LCA subtypes remain poorly understood. Here, using retina-specific affinity proteomics combined ultrastructure expansion microscopy (U-ExM), we reveal structural defects underlying type 5 (LCA5) nanoscale resolution. We show that...
Summary Cellular communication is critical for anti-cancer immunity, with tumor cell killing occurring at immunological synapses (IS) formed between effector immune cells and target cells. While optical super-resolution microscopy (SRM) has enlightened the spatial organization of IS mostly in regular cells, visualizing nanoscale architectural features its native state, including 3D receptor distribution ultrastructural details lytic granule release remains challenging. Using cryo-expansion...
Abstract Reproductive and respiratory organs, along with brain ventricles, are lined by multiciliated epithelial cells (MCC) that generate cilia-powered fluid flows. MCC hijack the centrosome duplication pathway to form hundreds of centrioles nucleate motile cilia. In these cells, large majority procentrioles formed associated partially characterized organelles called deuterosomes. We recently challenged paradigm deuterosomes de novo providing data, in MCC, suggesting they nucleated from...
Abstract Expansion microscopy is an approach of super-resolution fluorescence that does not yet achieve the precision nanoscopy techniques such as single-molecule light (SMLM). Here, we developed iterative ultrastructure expansion (iU-ExM), which now matches SMLM resolution demonstrated using standard references nuclear pores. Applicable to both cells and tissues, iU-ExM allows a broad research community access high microscopy.
Merkel cell polyomavirus (MCPyV) is the first clearly associated with a human cancer, i.e. carcinoma (MCC). Polyomaviruses are small naked DNA viruses that induce robust polyclonal antibody response against major capsid protein (VP1). However, VP1 epitopes have not been identified to date. The aim of this study was identify neutralizing MCPyV capsid. For goal, four mutants were generated by insertional mutagenesis in BC, DE, EF and HI loops between amino acids 88-89, 150-151, 189-190,...
Abstract Centrioles are essential microtubule-based organelles organizing cilia and centrosomes. Their mode of biogenesis is semi-conservative: each pre-existing centriole scaffolds the formation a new one, process coordinated with cell cycle. By contrast, multiciliated progenitors two centrosomal centrioles massively amplify to support nucleation hundred motile transport vital fluids. This occurs through type-specific called deuterosomes, composed centrosome-related elements, regulated by...
Abstract Multiciliated cells (MCCs) harbour dozens to hundreds of motile cilia, which beat in a synchronized and directional manner, thus generating hydrodynamic forces important animal physiology. In vertebrates, MCC differentiation critically depends on the synthesis release numerous centrioles by specialized structures called deuterosomes. Little is known about composition, organization regulation Here, single-cell RNA sequencing reveals that human deuterosome-stage MCCs are characterized...
Abstract Centriole number must be restricted to two in cycling cells avoid pathological cell divisions. Multiciliated (MCC), however, need produce a hundred or more centrioles nucleate the same of motile cilia required for fluid flow circulation. These are produced by highjacking cycle and centriole duplication programs. However, how MCC progenitor handles such massive finally organize them an apical basal body patch is unclear. Here, using new cellular models high-resolution imaging...
Abstract The stereotypic structure of microtubules, assembled from conserved α/β-tubulin dimers is subject to a complex diversity Post-translational Modifications (PTMs). PTMs are predicted fine-tune microtubule properties and interactions with other proteins, thus allowing microtubules perform specific functions. Cilia accumulate several types tubulin PTMs, such as polyglutamylation, polyglycylation, detyrosination acetylation, whose functions not yet fully understood. Recently, mutations...
Centriole number must be restricted to two in cycling cells avoid pathological cell divisions. Multiciliated (MCC), however, need produce a hundred or more centrioles nucleate the same of motile cilia required for fluid flow circulation. These are produced by highjacking cycle and centriole duplication programs. However, how MCC progenitor handles such massive finally organize them an apical basal body patch is unclear. Here, using new cellular models high-resolution imaging techniques, we...
Centriole number must be restricted to two in cycling cells avoid pathological cell divisions. Multiciliated (MCC), however, need produce a hundred or more centrioles nucleate the same of motile cilia required for fluid flow circulation. These are produced by highjacking cycle and centriole duplication programs. However, how MCC progenitor handles such massive finally organize them an apical basal body patch is unclear. Here, using new cellular models high-resolution imaging techniques, we...