On 1st and 2d February 2016 representatives from the sites of FBI Paris-Centre node met in the Eden Park Hotel of Pont l’Eveque (Normandy, France) to exchange about the implementation of their projects, identify local difficulties and needs, define a strategy and start to work on an action plan for the FBI Paris-Centre node.
For their first global meeting dedicated to the node, engineers and researchers from its different sites (Imagopole-Ultrapole, ImagoSeine, PICT-Curie, IBENS, Institut Curie, Institut Pasteur, ENS, Lab. de Neurophotonique – Univ. Paris Descartes, etc.) were joined by the IPDM team from Pasteur and the FBI national coordination team.

The retreat was organized in two main parts.
The first consisted of scientific and technical presentations of the various projects undertaken by the associated platforms and laboratories FBI, the progress of these projects and their integration into the general schema missions and program of the national distributed infrastructure. Charles Kervrann from INRIA Rennes and one of the responsible of the IPDM Node, was also invited to the retreat and presented the IPDM node (missions and goals of the node, overview of the results of the IPDM survey on-site led by Perrine Paul-Gilloteaux). These various sessions were then followed by informal and fruitful discussions.
The second part of the retreat was organized in workshops and parallel working groups (lead facilitators indicated); the themes were proposed in advance and the reviews were presented “on-the-spot” at the end of the meeting.

Below are some elements of reflections, proposals for action, scientific and technical projects undertaken or proposed during the workshops

WORKSHOP 1: CORE FACILITIES RUNNING (OLIVIER RENAUD)

• Organization of an annual meeting about Core Facilities management in order to optimize equipment management, overcome the saturation of technology, standardize administrative procedures, develop the quality of materials to the new standards (NF-X50-900)
• Creation of a form for tracking collaborations within and between FBI nodes
• Creation of a Data Base “experts”
• Proposals to be transmitted to WP “training”: develop and disseminate e-learning modules for users, development of training certificate room for personal Core Facilities

WORKSHOP 2: TECHNOLOGY TRANSFER (VALENTINA EMILIANI)

• To identify, pool and facilitate the access to existing resources (workshops, 3D printers…)
• To give priority to universal software solutions, develop software for private companies, use appropriate personal and dedicated
• To conduction an “FBI” action with the CS CNRS so as to develop technologies to make it a source of funding (patents)
• Develop training tools and tutorials to make time for platform engineers. Setting priorities with% time between service and R & D
• Solicit bids for systems duplication.

WORKSHOP 3: PARTNERSHIPS, JOINT ACTIVITIES AND OUTLOOK (LUDOVIC JULLIEN)

Action involving developers
• Metrology and benchmarking: reference samples, comparative studies protocols, image analysis procedures
• Thematic Appetizers for scientific foresight (educated biologists, newspaper publishers, guardianship)
• Drafting of collective reviews, comments on articles

Developers and platforms

• Action inventory and good collaborative practices for resource optimization
• Establishment of a generic alias
• Some readability rates platforms
• Inventory sensors and actuators optogenetic. Workshops back experience and foresight (CLEM bimodal probes for example)

Dissemination to non-specialists

• Core facilities: rather a place of advice than a place of technicians
• Short Videos (3 min) for the dissemination of new systems and instruments explaining what biologists could make users

WORKSHOP 4: DATA MANAGEMENT (STEPHANE DALLONGEVILLE & JEAN SALAMERO)

Proposals
• Establishment of a national portal with a Bio-Imaging database. This database will be used first to store data publications from FBI (projects funded or co-financed by FBI). In addition to giving visibility to the FBI inflows, this base is also intended to serve as a “gold standard” for the FBI users, both images themselves and the associated metadata. A reflection should be made on the choice and structure of metadata (OME model?) And the ontology to be used (see http://bioportal.bioontology.org/) to provide a model for the whole community.
• Implementation of the common API interoperability (as a web service) enabling communication between image analysis software and databases (among others). The portal will provide documentation and all necessary details for the implementation of this API for any center or institute may put in place on its own data management system (organization hackatons in this sense).
• Setting up a benchmarking platform for image processing algorithms by exploiting both the hardware “gold standard” of the database and API for accessing it (idea to dig).
• Reflection on storage strategies, choices, sorting, but also the visualization and analysis of its large images.

Training

• Train users to image analysis tools such stand-alone (Icy, Fiji, ImageJ …)
• Train users of analysis tools distributed cluster-type / grid computing (OpenMole, Galaxy / Mobile)
• Educate users to databases, provide a vision of the possibilities offered by these systems

On March 9th 2016 was held in Rehovot the kick-off meeting of the INFRADEV preparatory phase II (PPII) European project that aims at bringing EuroBioImaging to a functional European infrastructure (ESFRI) under the status of an ERIC. In that project, France (through FBI) is coordinating the WP7 « Training » that aims at preparing the organization and procedures of training activities, identification of training sites and portfolio of training courses and e-learning, for both users and core facility staff.
France presented the WP7 objectives, working plan, activities already under process: the creation of specific working groups on community surveys, interaction with industry and e-learning.
The next steps is to draft the surveys to analyse the needs and resources for training, and the organization of meetings of heads of EuroBioImaging node candidates as well as core facility staff to gather feedback on training organization.

This project runs for two years with a 1.5 M€ funding and will develop close ties with other projects in which EuroBioImaging is involved such as the Global BioImaging project or linked to, such as the “Neubias” COST action.
Through these projects, France continues to reinforce its position in EuroBioImaging by the demonstration of its capacity to organise, structure and provide training activities.

Paris, January 22, 2016

Over the case studies presented by the three infrastructures, it appears that the life-science data deluge and in particular Image Data, causes processing and management issues in terms of volume, formats and numbers of parameters to integrate. However, the challenge to find ways to share and analyze the diversity of Biological Data will unquestionably lead, to scientific and medical advances previously impossible. Indeed, the trans-dimensional understanding of the living organisms that such a “Big Data” approach should bring, will allow a multi-scale view of biological mechanisms and provide new tools for the prevention and diagnosis of diseases.

Organization, integration, description and harmonization are essential for the best use, comparison and interoperability of the heterogeneous and large data sets produced by the different fields of Biomedical Sciences. It is therefore necessary to have standards in all stages of processing and validation in a context where most of the formats are not suitable for very large and/or complex data. For this purpose, it was decided to set up inter-INBS think tanks with the aim to develop common projects:

(1) To explain the specific locks and identify means to solve them
(2) To Illustrate on “study case” projects the added value of a joint work
(3) To make recommendations for Big Data management in the Life Sciences Area

 

For the second time since their creation, the National Infrastructures laureate of the PIA 2011 and 2012, met in November 2015, under the auspice of the ANR. After short introductions on the evaluation modalities of the INBS by ANR (D. Boujard) and presentation of the new National and European Roadmaps for Research infrastructures (E. Guittet), this one day meeting was organized around four Round Tables: Implementation and monitoring of evaluation indicators, inter Infrastructures cooperation, Communication policy: towards a common portal ?, Pricing: common calculation modalities.

Ministry of High Education and Research (MESR) recently nominated France-BioImaging as the unique French Node for the European ESFRI project, Euro-BioImaging. FBI was already evaluated as a “Highly Recommended” primary node for EuBI by an international and independent Evaluation Board. FBI is thus candidate as one of the First generation Nodes, part of the European Infrastructure. EuBI is now entering in a very intense consultation and negotiation step. Both MESR and CNRS are deeply involved and their representatives actively participate to EuBI Interim Board meetings, side by side with FBI.

This last Year, France BioImaging was deeply involved in the building of H2020 infrastructure projects, within the context of the Euro-BioImaging ESFRI project. D. Choquet (Bordeaux) and PF. Lenne (Marseille) are our official representatives at the EuBI Interim Board, with Daniel Boujard for the CNRS (see previous article). However, FBI does not restrict its International and European activity to EuBI.

France-BioImaging will represent the CNRS partner of the H2020 Infra-Dev Supp II Project recently funded by EU, and proposed by EuroBioImaging (EuBI). In coordination with other national networks and international partners, France BioImaging will actively participates in diverse WPs and in particular will lead the WP7: Technical preparation for coordination of training activities.

Objectives:

1. Preparation for coordination of user training in EuBI (EMBL, CNRS)
2. Preparation for coordination of core facility staff (CFS) training in EuBI (CNRS)
3. Prepare CFS online training and exchange resources

 
There is two other H2020 projects where France–BioImaging is involved. The first concerns a more “international network activity” on training and exchange activities, still in the context of EuBI. This project will be apparently funded, but is still under negotiations with the European Commission. The, last but not least, project is a “Cost” on BioImage Analysis, defended by 45 individuals from 17 different countries, with a strong participation of FBI members (pending decision,next October).

The 3rd France BioImaging Annual Meeting was held at the Institut Curie (PARIS), the 17th and 18th of September 2015. It gathered more than 200 attendees from all the FBI community and beyond. This year, the FBI-AM started by a few hours Community Meeting. During this session the national coordination (M. Coppey and J. Salamero) made a short report of the last year and an half, on main activities performed by and within FBI. A more general and open debate with the audience and in particular with representatives of the National Advisory and National User committees, followed. A number of crucial issues concerning next steps in FBI building and sustainability, its transparency, as well as information on a number of governance adjustments made over the last year, were evoked. Now that FBI entered in its functioning part (since end of 2014), a stronger effort should be made to the operation of the Infrastructure. This morning session was completed the day after by a short presentation (D. Choquet) of FBI participation to H2020 calls (Europe Group) and involvement in the Euro BioImaging ESFRI project. Then, the Scientific part of the Meeting started with an exciting and fascinating conference by E. Betzig (Laureate of the Nobel Prize of Chemistry 2014), mainly covering the latest progresses in High Space-Time Resolution microscopy and emphasizing the power to combine Light Sheet and Structured Illumination Microscopy (Lattice Light Sheet Microscope)
 

Clemens Kaminski (Cambridge, UK) was the external invited speaker of this session. His work and presentation focused on the use of nanoscopy approaches to decipher molecular mechanism of disease and in particular on protein misfolding and aggregation in neurodegeneration. One WP1a Group in Bordeaux node showed that using well-designed optical lattices for depletion together with wide-field excitation and a fast camera for detection, large parallelization of STED nanoscopy is achievable (700 doughnuts). In this context polarization effects were thoroughly studied. Another one showed how a single high numerical aperture objective can be used to produce an excitation light sheet perpendicular to the optical axis for optimal sectioning and high background rejection (soSPIM for single objective Selective Plane Illumination Microscopy). soSPIM imaging applications, from whole drosophila embryos down to the single cell level with single molecule detection sensitivity up to 30 µm inside the sample, illustrated the performance of this new technology. The final presentation covered the mechanisms of DNA segregation in bacteria, which is a critical process for the faithful inheritance of genomic information for all life forms. The positioning, organization and transport of the underlying molecular components were revealed by super-resolution microscopy techniques including 3D SIM, PALM and optical deconvolution.
 

After a quick presentation of the group, this session hosted guest speaker Gerard Marriott (UC Berkeley) who presented new developments of fluorescent probes optimized for fluorescence anisotropy and FRET microscopies. He emphasized on the advantages of using fluorescence anisotropy to detect biomolecular interactions in live cells thanks to its ability to report associated changes in protein complexes rotational diffusion. His talk was followed by three short talks from WG1 b members describing recent study of G-protein coupled receptors GABA(B) oligomerization using multiphoton scanning imaging coupled with Number & Brightness analysis method, advances and applications of polarization-resolved microscopy to unravel structural information in live cells and results on the molecular mechanisms of rigidity sensing at focal adhesions using fluorescence fluctuation spectroscopy and FLIM-FRET imaging.
 

The session was introduced by Y. Schwab, Group Leader and EM-facility Head at EMBL, Heidelberg. During his talk he described, among other approaches and applications, the “full-Correlative Light Electron Microscopy” strategy his team developed to image single tumor cell within living animals and how to correlate it at the EM scale with the contextual environment. Members of the WP1c then showed diverse ongoing developments and applications on CLEM approaches, emphasizing the interest 1) of Focus Ion Beam-SEM technique 2) to automate sample preparation and preservation 3) to introduce BioImage Informatics in the CLEM workflow 4) and to enlarge the “bottle neck” of the massive data sets generated by high resolution 3D EM.
 

This working group invited Prof Dan Oron from the Weizmann Institute of Science (Rehovot, Israel) that gave a presentation on semiconductor nanocrystals as new probes for nonlinear imaging in deep tissues. These new crystals show promising properties and can lead to new contrast mechanism such as upconversion. Four highlights have been presented by WG1d group leaders on fast imaging in brain using acousto-optics, multicolor multi-photon imaging in brain and the use of fibers for single and multiphoton imaging. Although the WG1d is still active in multiphoton nonlinear developments, it is working on a new direction to develop fiber probes and endoscopes to provide ultra-short pulses at the sample plane and to collect the backscattered nonlinear signals. Applications are foreseen primarily in neurobiology for deep brain investigation.
 

In this session, two external speakers were invited to give talks. First speaker of the session was Rafael Carazo Salas, group leader at Cambridge University, and a major figure in the European HCS landscape. He spoke about his efforts to systematically study fundamental cellular processes in yeast, such as cell division, regulation of the cytoskeleton and morphogenesis, with a focus on the link between these processes. He also presented a very recent study on using HCS for pathway reconstruction by specifically probing for the influence of gene knockouts on protein localization. Second speaker was Xavier Gidrol, director of research at CEA Grenoble, where he leads the Biomics lab. He spoke about more translational aspects of High Content Screening, focusing on the study of proliferation / differentiation balance in carcinogenesis, for which he uses “lensfree” imaging.
The session was completed by three short talks from the WG2 presenting the RUSH system, which is a scalable assay design for the study of protein trafficking andan application of this system for the identification of chemical inhibitors of protein transport, strategies for large scale studies in the field of spatial transcriptomics, i.e. the study of transcript localization in cells and Bioimage Informatics approaches for phenomics, i.e. tools for the computational analysis of HCS data.
 

The purpose of the session was to provide an overview of the current activity covered by the chemists of the WP3. Eleven speakers from both inside or outside of the FBI INBS gave flash presentations focused on one specific work, from development on new fluorescent proteins for Super Resolution Localization Microscopy up to the use of lanthanides for NIR imaging in animals. This “Chemist in Action” speed dating is summarized in a small booklet (see the Booklet WP3).
 

As an external lecturer, Erik Meijering (Erasmus Univ, Rotterdam) presented the “community effort” made in the “BioImage Analysis” area over the last years. He described different types of “challenges” aimed at comparing tracking image processing and analysis methods, on simulated data sets and also on real data sets. The comparative results using a number of criteria are made publically available some are published in peer reviewed journals and provide the backbone of future integrated methods for image analysis. Three groups of FBI WP4 speakers followed who 1) illustrated new developments in Bioimage-Informatics aimed at quantifying dynamic activities in single cells, 2) presented concerns on the “Image Life Cycle” in the FBI community and an “Icy community” report. Finally 3), two “user-cases” of the software and analysis tools provided through the FBI infrastructure, were presented.
 

Working Group 5 is now separated in two parts. “Dissemination and communication” are primary responsibilities of the coordination, while “training and education” actions should be shared and promoted by the overall community. Following comments from our Scientific Advisory Board ( March 2014), FBI was very active this last year and an half, as testified by an increasing number of FBI presentation, participation, organization and support of conferences, workshops, training courses in our area of interest (MIFOBIO, RTs, FBI-AT, SMLMS, EuBIAS, QBI…) and beyond (SBCF, FEBS-EMBO, ITMO-TS…). Multiple examples illustrating these past and future activities were presented by FBI members. A “technology transfer” strategy will have to be defined in the near future through the rules of the “Consortium Agreement” (signed by all Parties in summer 2015).

Since September 2015, the National Coordination of France BioImaging is identified as an official UMS entity, called “CEMIBIO” (UMS 3714) and retroactively created for the 1st of January 2015. At this stage it is simply a small support structure created between CNRS and Institut Curie. Jean Salamero was nominated as the director, Corinne Tessier, who was hired in June 2015, is our Administrative officer, and Juliette Gallois our webmaster & communication officer. A good start for the opening of the operational phase of France BioImaging !
 

Jean SALAMERO (PhD)
FBI National Coordinator
Dir. of UMS 3714 – CEMIBIO, CNRS – Institut Curie
jean.salamero@france-bioimaging.org

Corinne TESSIER
Administrative Officer
UMS 3714 – CEMIBIO, CNRS – Institut Curie
corinne.tessier@france-bioimaging.org

Juliette GALLOIS
Communication Manager
UMS 3714 – CEMIBIO, CNRS – Institut Curie
juliette.gallois@france-bioimaging.org

Three INBSs, FRISBI (Integrated Structural Biology), Phenomin (Mouse phenogenomics) and FBI (Bio-Imaging), laureates of the “Programme Investissement d’Avenir” in 2011, previously decided to explore possible common activities (see article). The idea, that our INBSs could better interact, think of common projects or services and organize joint actions, was now extended at the FBI Annual Meeting (17th- 18th of September, Institut Curie, Paris) during a dedicated “Inter INBS” session. Bruno Klaholz (IGBMC, Illkirch), the Coordinator of FRISBI, briefly presented the diverse activity of its infrastructure, including operational modality and more importantly, complementary or common technological approaches with FBI. Possible transverse activities aimed at integrating multi-scales data appear obvious. This should lead to common actions notably with the WP1c (CLEM/super-CLEM), WP1a (High Resolution) and WP4 (Bioimage Informatics-IPDM). In her talk, Emilie Audran (IGBMC, Illkirch), explains the mission of Phenomin. To improve the knowledge of the mammalian genome, identify and understand its variations and discover new opportunities for therapies and drugs. Imaging is an obvious technology in this context, and clear connections are possible with the FBI WP1d (New contrast and In-Depth Imaging). Beside these technological and scientific common interests, these three INBS also share concerns about their future and sustainability, beyond the end of the PIA program. Next step is now to develop common programs and actions as defined by the obvious overlaps and complementarity above.

The 1st of July, the national coordination was invited to give a general presentation of FBI to the Advisory Committee of the ITMO-TS (Technologies pour la Santé). A number of members of the INBS FLI (France Life Imaging) were present. Following the presentation both parties agreed that we should finally start to engage common “building sites”. A first one will be a common meeting held in Paris the 30th of September, between FBI, FLI and l’IBF (Institut Français de Bioinformatique (another INBS of the PIA 2012) which topic will be the organization of a more general workshop on:

1) Which IT infrastructures for Imaging Data?
2) Ethical (and security) issues in the context of data management, sharing, dissemination
3) Business Plan prospective and PIA 2016/H2020 common actions.

The development of an “out-reaching” strategy, is a strong recommendation of our international Scientific Advisory Board. The last year and an half, FBI was thus particularly active in promoting the French BioImaging Community and in particular FBI activities to a broad scientific community (FEBS-EMBO satellite symposium, SBCF meeting, in many international conferences, organized or co-organized by FBI …). Next date in the FBI agenda, FBI will be presented to the scientific Board of the ITMO-BCDE (Biologie Cellulaire , du Développement et Evolution) at Aviesan.

The first Annual Meeting of the Infrastructures Nationales en Biologie Santé (INBS) was hold at CNRS, 9th December 2014. The aim of this meeting was to prepare the actualization of the Research Infrastructures road map defined in the National Strategy of the Research Infrastructures 2012-2020 by the DGRI (Direction Générale de la Recherche et de l’Innovation, National Ministry).

 

The general policy of the National Strategy of the Research Infrastructures 2012-2020 is to:

• be leader in the construction of European Infrastructures
• increase French participation in advanced international programs
• assist the needs of research community in all activity domains
• reinforce partnerships between economical suppliers and users

 

23 INBS are recognized:

• ANAEE (Analyse et expérimentation sur les écosystèmes-Service)
• BIOBANQUES
• CONSTANCES (Infrastructure épidémiologique ouverte pour la recherche et la surveillance)
• CRB ANIM (Réseau de centres de ressources biologiques pour les animaux domestiques)
• E-CELL France (Infrastructure nationale de médecine régénératrice basée sur les cellules souches mésenchymateuses)
• EMBRC France (Centre national de ressources biologiques marines)
• E-RECOLNAT (Valorisation de 350 ans de collections d’histoire naturelle : une plateforme numérique pour l’environnement et la société)
• F-CRIN (French Clinical Research Infrastructure Network)
• FLI (The French National Research Infrastructure for Medical Imaging)
• France BIOIMAGING (The French National Research Infrastructure for Biological Imaging)
• France GENOMIQUE
• France HADRON (Hadronthérapie)
• FRISBI (Infrastructure Française pour la biologie structurale intégrée)
• HIDDEN (Infrastructure de recherche dédiée aux maladies hautement infectieuses)
• IDMIT (Infrastructure nationale pour la modélisation des maladies infectieuses humaines et les thérapies innovantes)
• IFB (Institut Français de bioinformatique)
• INGESTEM (Infrastructure nationale d’ingénierie des cellules souches pluripotentes)
• METABOHUB (Infrastructure nationale en métabolomique et fluxomique)
• NEURATRIS (Infrastructure de recherche translationnelle pour les biothérapies en neurosciences)
• PHENOME (Centre Français de phénomique végétale)
• PHENOMIN (Infrastructure nationale en phénogénomique de la souris)
• PROFI (Infrastructure Française de protéomique)
• TEFOR (Transgenèse pour les études fonctionnelles sur les organismes modèles)

An analysis is conducted by AVIESAN (http://www.aviesan.fr/) and ARIIS (http://www.ariis.fr/) about an outline of good practices of different types of service offer in the context of public-private partnership.

The C-CRAFT software for segmentation of particles and estimation of background fluorescence in 2D and 3D live cell imaging, was developed by the Serpico Team at Inria de Rennes, a member of the FBI-IPDM ( Bioimage informatics-Image Processing and Data Management) transversal node . See also http://mobyle-serpico.rennes.inria.fr/

ICY is an open community platform for bioimage informatics developped at Institut Pasteur in the frame of “FBI-IPDM” projects. It gathers software ressources to visualize, annotate and quantify bioimaging data.

A team work, dear to the policies and objectives of France-BioImaging !

 

The 30th of January 2015, coordination staffs of 3 INBSs, laureates of the “Programme Investissement d’Avenir” in 2011 (FRISBI, Phenomin and FBI), get together for an informal meeting at IGBMC, Illkirch. The idea, that our INBSs could better interact, think of common projects or services and organize joint actions, was born during the INBSs meeting organized at the CNRS, in December 2014. Although at a very early stage, cooperation is definitively foreseen between FRISBI (Integrated Structural Biology), Phenomin (Mouse phenogenomics) and FBI (Bio-Imaging). Complementary or common technological approaches appear obvious. A shared session between the 3 Infrastructures will be organized during the next FBI Annual Meeting (17th- 18th of September, Institut Curie, Paris) with the goal to consider possible transverse activities.

 

 

The French Infrastructure for Integrated Structural Biology (FRISBI) provides an infrastructure for integrative structural biology approaches, from the molecular to the cellular level, integrating multi-resolution data from X-ray crystallography, small angle X-ray scattering, NMR, Cryo-EM and functional data including development for protein expression and crystallization. Opened to structural and molecular and cell biologists from both academia and industry from France and Europe FRISBI will reinforce technology transfer between national and international academics and industry for technological developments and therapeutically applications. FRISBI comprises strong component for training in integrative structural biology by the organization of congress, workshops & practical courses, and national and international master degree program.

PHENOMIN is devoted to serve the French community for the usage of mouse models. This National Infrastructure constitutes a unique distributed resource for the creation, the care, the phenotyping, the distribution and archiving of animal models for academics and private corporations. Its scientific goals are to improve the knowledge of the mammalian genome, identify and understand its variations and discover new opportunities for therapies and drugs. PHENOMIN will also participate to the International Mouse Phenotyping Consortium (IMPC) and plans to contribute to Infrafrontier and to ESFRI-identified pan-European infrastructure for functional genomics. PHENOMIN will be a key item of the the National Alliance for life sciences and health (AVIESAN).

France-BioImaging (FBI) gathers several biological Imaging Centers associated with R&D teams with the aim to cover recent advances in microscopy, spectroscopy, probe engineering, signal processing and BioImage Informatic. It is a pluridisciplinary project with participants in Biology, Physics, Chemistry, Computer science and engineering. The consortium brings together the efforts to overcome technological barriers persisting at different levels of Cellular Imaging and breaks the frontiers between research and innovation thanks to collaborative projects with industry. France Bioimaging is strongly involved in the strategy of the ITMOs BCDE of Aviesan through the French Networks of the CNRS (GDR-MIV) and directly linked to the “Euro-BioImaging” project of ESFRI.