THE FRENCH NATIONAL RESEARCH INFRASTRUCTURE FOR BIOLOGICAL IMAGING 1 • Funded through the « Investissements d’Avenir 26M€ through 2019 • Objectives • EXPAND THE FRONTIERS OF KNOWLEDGE IN LIFE SCIENCES • STRENGTHEN ATTRACTIVENESS AND COMPETITIVENESS OF FRANCE • BRING TOGETHER RESEARCH AND INNOVATION • SUSTAIN TRAINING AND DISSEMINATION FRANCE-BIOIMAGING.ORG - [email protected] 2 France BioImaging The French National Research Infrastructure for Biological Imaging Scientific results already obtained and published Promoting active WGs as an operational task force Scientific Innovation COORDINATING TRAINING & DISSEMINATION  Enhance Expertise in Biological Imaging PROGRESS IN TECHNOLOGY ACCESSIBILITY: SERVICE OFFERING To the National & International Community Global Scientific Progress Technol. Innovation Positioning in Europe RESEARCH & DEVELOPMENT In partnership with industry  Creation of innovative tools to study Life  Creation of Companies  Creation of Employment Societal Innovation To the Industry  Innovations in the Therapeutic, Cosmetic, Agronomic, (...) fields  for the benefit of the Society France BioImaging, a multi-sited node in the EuroBioImaging ESFRI project FOUNDATION Industrial partners IBiSA Infrastructures Cellular imaging From molecules to whole organisms Super resolution, Dynamics, Interactions, Multiscale imaging IBiSA CRITERIA Training & Dissemination TEACHING & DISSEMINATION RESEARCH & DEVELOPMENT R&D teams State of the art technologies Optique, Microscopy, Spectroscopy, Chemical probes, Image processing National & International networks OPENING Academic & Industrial users Research applications In physiology, cellular biology, developmental biology, pathologies (neurology, immunology, cancer) EquiPex Labex 4 FRANCE-BIOIMAGING INFRASTRUCTURE 5 LOCAL NODES & 1 TRANSVERSAL NODE Paris Centre, Ile de France Sud, Bordeaux, Marseille, Montpellier Inria (Rennes) / Institut Pasteur 10 IMAGING CORE FACILITIES IMACHEM INSTITUTIONAL PARTNERS CNRS - leading partner Inria, INSERM, Institut Curie, Institut Pasteur, Ecole Normale Supérieure, Ecole Polytechnique, Université Aix-Marseille, Bordeaux, Montpellier 1 & 2, Paris Descartes, Paris Diderot, Paris Sud Continuum between Cell biology Imaging and Medical Imaging From single molecules - to cells - to tissues - to organs - to animals and humans Embryo & small animal models FBI FLI 6 5 WORK PACKAGES WP2 High Throughput & High Content Screening E. Bertrand; T. Walter WP3 Probe Development, Optomanipulation & Optogenetics L. Julien; M. Sainlos WP1 Instrumentation & Methods WP4 Bioimage Informatics Image Processing & Data Manipulation WP5 Training, Dissemination & Technological Transfer JC Olivo-Marin; C. Kervrann L. Heliot; C. Poujol; J. Salamero 7 5 WORK PACKAGES – WP1 SUPER RESOLUTION IN LIGHT MICROSCOPY WP 1a: Super Resolution & Single Molecule Tracking L. Cognet; M. Dahan; V. Nägerl PhotoActivated Localization Microscopy (PALM), STochastic Optical Reconstruction Microscopy (STORM), Structured-Illumination Microscopy (SIM), STimulatedEmission-Depletion (STED), Single Particule Tracking-PALM (SPT-PALM) … FUNCTIONAL IMAGING WP 1b: Functional Imaging N. Borghi; D. Marguet; E. Margeat WP 1c: CLEM & Super CLEM P. Moreau; G. Raposo; B. Satiat-Jeunemaitre Alternating-Laser Excitation-Fluorescence Resonance Energy Transfer (ALEX-FRET), Fluorescence-Lifetime Imaging Microscopy (FLIM), Fluorescence Anisotropy Imaging Microscopy (FAIM), Fluorescence Correlation Spectroscopy (FCS), Fluorescence Cross-Correlation Spectroscopy (FCCS), Image Correlation Spectroscopy (ICS) … MULTISCALE AND MULTIMODAL IMAGING Correlative Light-Electron Microscopy (CLEM) & Super resolution CLEM LABEL & LABEL-FREE NEW CONTRASTS WP 1d: New Contrast & InDepth Imaging E. Beaurepaire; V. Emiliani, H. Rigneault Second-Harmonic Generation (SHG) microscopy, Third-Harmonic Generation (THG) microscopy, Coherent Anti-stokes Raman Scattering (CARS) microscopy … IN DEPTH OPTICAL IMAGING 8 Two/Three-Photon Excitation (2/3-PE) microscopy, Optical Parametric Oscillator (OPO), Single Plane Illumination Microscopy (SPIM) … Paris Centre (141) Salamero, M Coppey-Moisan TJECHNOLOGICAL OVERVIEW Institut Curie / PICT J. Salamero Institut Curie Physics M. Dahan Institut Jacques Monod / ImagoSeine M. Coppey-Moisan O. Faklaris IBENS / ImaChem Institut Pasteur / ImagoPole S. Shorte A. Triller ENS Chemistry L. Jullien Paris Descartes V. Emiliani Multi scale, multi modal & multi organism imaging - Cell biology & cancerology BioImage informatics - Image Processing and Data Manipulation (28) JC. Olivo-Marin (Institut Pasteur), C. Kervrann (Inria, Rennes) Image and signal processing, analysis, quantification and modeling Bordeaux (78) D. Choquet Super resolution & CLEM – Neuronal pathologies & plant physiology Montpellier (27) M. Nollmann Super resolution, Functional Imaging & HTS/HCS - Genome function analysis IdF Sud (24) N. Peyriéras In-Depth Imaging & IPDM – Morphogenesis analysis Marseille (35) PF. Lenne Super resolution, Functional & In-Depth Imaging Developmental biology & immunology 9 Aims of WP 1A Extending superresolution microscopy to 3D imaging • Multi-plane imaging, astigmatism, double-helices PSF,… Pushing further the spatial & temporal resolution • Development of bright probes, advanced computational tools, … Allowing long-term (> min) single molecule tracking • Gold nanoparticles, carbon nanotube imaging,… Extend superresolution & SMT capabilities beyond cultured cells • single plane illumination strategies, multi Gaussian beam, NIR imaging,… Enhancing color contrast and spectral flexibility • PALM, STORM, uPAINT,… Combine superresolution and EM, patch-Clamp, Photocontrol, … 10 Aims of WP 1B Extending biosensors capabilities • development of FRET-based biosensors: biochemical activities, tension, post-translational modifications, metabolites ,… Pushing further the spatial & temporal resolution of FLIM for monitoring transient interactions • Development of bright probes, multi focal excitation, time-resolved detector, single molecule FRET ALEX… Extend spectroscopy beyond cultured cells • single plane illumination FCS, NIR imaging,… Enhancing sensitivity of fluctuations based spectroscopy • Spot variation FCS, plasmon resonnance, STED-FCS,… Combine FRAP, Fluorescence fluctuations based spectroscopy and FLIM • ms to sec range of macromolecules dynamics and turnover… 11 Aims of WP 1C Correlate Multiscale Imaging data (Light and Electron Microscopy) to explore biological processes « in situ » Mastering methods to preserve fluorescent signals through the different steps of specimen preparations for Transmission Electron Microscopy Studies (TEM) : very different specimens, different probes …….. Improve the CLEM worflow to handle simultaneous observations at different scales: creating novel tools and equipements Develop Super-CLEM Image registration methods – improve correlation between images recorded at different scale Handling the data flow generated by such approaches SIM 2µ m SEM 2µ m 12 To develop innovative photonic tools to perform in depth imaging in microscopy and endoscopy. Axis 1: study of novel contrast mechanisms that do not rely on conventional refractive, absorption or fluorescence contrast mechanisms Axis 2: developing new methodologies and instruments that can extend the imaging depth of current techniques WG1d is ahead of available commercial systems and therefore relies on the physical/engineering core expertise of FBI Laboratories. Probing lipid orientation with THG. Polytechnique LOB. Phys Rev X 2013. 13 SERVICE OFFERING France-BioImaging.org  USE OF SYSTEMS General ALM Technologies Superresolution microscopiy Fluorescence spectroscopy (macromolecules dynamics and interactions in live organisms) Multimodal microscopy (CLEM) In depth &new contrast Imaging  DATA STORAGE & IMAGE ANALYSIS  BIOPROBES  TEMPORARY DISPOSAL OF PREMISES & EQUIPMENTS 14 ADDED VALUE - INNOVATIVE TECHNOLOGIES 33% OF INNOVATIVE TECHNOLOGIES ARE FUNDED BY FBI Innovative Technologies Instrument number 17 ADDED VALUE - TECHNOLOGY OPENING Instruments number PROGRESS IN INNOVATIVE TECHNOLOGY ACCESSIBILITY 18 ADDED VALUE - SCIENTIFIC AND SOCIO-ECONOMIC PRODUCTION Ye a r N u m be r of use r s N u m be r of pe r sons t r a in e d on sit e Ut iliza t ion r a t e of t h e in fr a st r u ct u r e N um be r of pu blica t ion s ( FBI cit e d ) N u m be r of pa t e n t s ( FBI cit e d ) by users by FBI members for developments or maintenance from FBI members from users from FBI members from users 2012 2078 1064 38,3% 41,5% 1 0 0 0 2013 3515 1586 46,2% 42,2% 40 3 3 0 Publications: 36 + 2 (IINS) distinct publications in which FBI is acknowledged Patents: 2 deposited (Institut Fresnel) & 3 under review (CIML, Pasteur) Creation of a Start-Up CRYOCAPCELL by Xavier Heiligenstein (“Prix Creation Innovante CREACC 2013” and “Lauréat Tremplin Entreprise 2013” ) 19 ADDED VALUE - DISSEMINATION FBI SPECIALS EXTERNAL EVENTS FBI Kick-Off meeting, MiFoBio 2012, FBI-AT 201 ELMI 2013, EMBO Course on Super Resolution, Assises du RTmFm FRANCE BIOIMAGING ADVANCED TRAINING FBI-AT - 2013 ◎ 3D+time imaging of developing model organisms ◎ Membrane proteins imaging in plant cells Superresolution imaging ◎ ◎ ◎ Bioimage informatics Molecular dynamics ◎ Biosensors IMAGIF Gif-sur-Yvette - France December 9th to 13th + MicroCOR Winter School, CLEM Days, RUE 2013, EuBI Worskshop on Training… 20 EXPAND THE FRONTIERS OF KNOWLEDGE IN LIFE SCIENCES STRENGTHEN ATTRACTIVENESS AND COMPETITIVENESS OF FRANCE BRING TOGETHER RESEARCH AND INNOVATION SUSTAIN TRAINING AND DISSEMINATION FRANCE-BIOIMAGING.ORG - [email protected] 21