Team 4 of the Inserm research unit 1245 aims to characterize the contribution of neurovascular dysfunction in the pathophysiology of neonatal brain lesions while keeping in mind brain immaturity. Thereby, research projects paid attention to molecular, cellular and integrated processes leading to angiogenesis defects and neurodevelopmental consequences such as vessel-associated migration. The team’s research activity is deeply committed into translational research validated by patents and clinical protocols with the objective to develop diagnosis tools and neuroprotection strategies. To reach these objectives, the research team developed mouse perinatal models of white matter injury, in utero gain and loss of functions, and environmental models of fetal toxicity such as FASD. Endothelial and neuro-vascular dysfunctions are apprehended in the developing brains and retinas by imaging approaches (light sheet, FLIM-STED, time-lapse migration, in situ zymography, OCT) on ex vivo tissues (brain organotypic slices, cultured retinas). Image processing and analysis through notably machine learning is developed in partnership with several members of the Normandy FBI node.
3D-electron microscopy approaches and correlative microscopies at different scales, from single molecules to tissues. Strong expertise in molecular imaging by cryo-EM and single particle analysis
The team develops original systems to fluorescently label and track DNA (ANCHOR technology – NeoVirtech SAS) in real time at nanoscale resolution to understand physical principles underlying regulation of gene expression and DNA repair, in cellular plasticity and tumorigenesis.
As part of the Integrated Structural Biology platform at the Centre for Integrative Biology (hosting the national and European Infrastructures FRISBI, Instruct-ERIC and iNEXT-Discovery), and our research group at CBI/IGBMC we have recently done a series of developments in super-resolution fluorescence microscopy to facilitate single molecule localization microscopy (SMLM) analysis with the aim of integrating structural data generated through crystallography, cryo-EM, cryo-ET and FIB towards the cellular level (Biol Cell., 2017). We developed an integrated software for image reconstruction, drift & chromatic aberration correction, co-localization, resolution estimation (SharpViSu; Bioinformatics 2016), segmentation & clustering of labeled complexes [ClusterViSu;4], including 3D analysis and segmentation of SMLM data using Voronoi diagrams [3], as summarized in a book chapter [1]. Our latest development comprises a spectral demixing method which facilitates co-localization of proteins in SMLM (https://doi.org/10.1101/2021.12.23.473862).
The QuESt imaging facility combines the microscopy resources of the Institut de Génétique et Biologie Moléculaire (IGBMC) and the Laboratoire de Bioimagerie et Pathologies (PIQ). The two laboratories are located on the Illkirch bio-campus, just 10 minutes’ walk from each other. QuESt has held the IBiSA label since 2014. QuEst offers a range of instruments for multi-scale imaging, from the molecule to the whole animal. The ICI (Imaging Center IGBMC) component located at the IGBMC specialises in imaging the dynamic processes of living organisms at the molecular, cellular and whole organism levels. Researchers can analyse, in an integrated manner, their study models at different resolutions, ranging from the finest cellular structures to the complex functioning of organs in vivo. The PIQ (Plateforme d’Imagerie Quantitative – Quantitative Imaging Platform), located in the Faculty of Pharmacy, has a specific focus on quantitative molecular microscopy methods. In addition to commercial instruments, the PIQ-QuESt develops its own state-of-the-art instruments.
Microscopy systems available @QuESt
The microscopy facility was the first technology platform established in the IBMP in 1998. Its scientific programme aims at understanding the expression of plant or animal genes over space and time at various levels. Microorganisms or biomaterials studied by partner research units are other topics of interest. Our facility follows official guidelines for « Plates-Formes Technologiques du Vivant » and has received RIO 2001, 2004 and 2006 labels. It’s part of the larger PIC.sc Strasbourg Centre Cell Imaging Facility that allows sharing devices and knowledge from several research units from CNRS, INSERM, UNISTRA. Our missions include assisting research from IBMP and partner research units, developing and implement new imaging technologies, training our user base and beyond, getting involved in microscopy education and science popularization.