We are very pleased to share France-BioImaging Activity Report 2021-2022 with the broad community.
Browse through it and discover France-BioImaging activities, our Nodes, our users’ projects, our governance and our achievements in 2021-2022.
You can also view and download the document as a PDF here.
The previous activity report is also available right here, check it out!
Have a great reading!
France-BioImaging primary mission is to develop, promote, disseminate and provide access to innovative instruments and imaging technologies in the field of bioimaging to scientists. Fostering the technological transfers is at the heart of this mission, and for this France-BioImaging relies on a strong association of leading R&D research teams with core facilities.
However, several bottlenecks exist and often hamper or prevent successful technology transfer:
As a way to tackle these bottlenecks, France-BioImaging launched in January 2021 its first “FBI Internal Call 2021: Technology transfer from the R&D teams to the core facilities” to promote the transfer of new technologies (instrumentation, probes, staining methods, software, data analysis or data visualization) from the R&D teams to the facilities of France-BioImaging, for access and service to end-users. The outcome of the transfer project had to ensure for the prototype to be usable by the end-users until the interpretation of the data. The project had also to include a sustainability plan and a training plan to guide both facility staff and end-users toward autonomy.
The project selection was organized by the National Coordination of France-BioImaging and applications were assessed according to the following evaluation criteria:
For the first edition of the “FBI Internal Call 2021: Technology transfer from the R&D teams to the core facilities”, 5 projects were selected:
The call was renewed for another edition in 2022! Here are the 7 laureates:
Each selected project was awarded with a 80k€ grant for salary and/or equipment, and several positions are currently available: https://france-bioimaging.org/jobs/
This event, organized by the Bioimaging axis and the Image analysis working group of Biogenouest, will take place at Pôle Numérique Rennes Villejean, on October 4th, 2023.
It will be divided into 4 parts:
Three lectures:
Two small-group workshops followed by plenary feedback sessions
A pitch session to present image processing issues on your platform
A poster session over lunch
Please register before September 15th, 2023 on the following link: docs.google.com/forms/d/e/1FAIpQLSfkyXjNvYInLjU0v0WPOd10PFsufjDy3uoVpnhr9avNMVJZzw/viewform
Our National Coordination visited 2 of our 9 nodes in one week: the Montpellier node and the Ile-de-France Sud node!
This visit was the perfect occasion to have a look on the broad range of technologies and expertise both nodes are providing in open access to their users. They cover a multitude of imaging techniques in electron microscopy, light microscopy and cytometry and working on various models going from the single cell to small animals. Besides, they both provide excellent services in – of course – imaging expertise, but also in sample preparation and bioimage analysis.
Furthermore, we discussed about the future of the nodes and their promising perspectives. The core facilities and R&D teams are working towards novel innovative imaging technologies that, we hope, will be in open access very soon!
Thank you to all of the following core facilities and R&D teams for the warm welcome:
We were happy to meet everyone! Until next time!
Photos from our visit at the Montpellier node:
Photos from our visit at the Ile-de-France Sud node:
We are happy to announce that our 1st Africa-France Joint Initiative for Biological Imaging calls, in coordination with the African BioImaging Consortium and Imaging Africa, is funding 11 projects!
As a reminder, these two calls (“External access” and “Twinning exchange”) have been primarily designed to strengthen collaboration between African and French researchers and engineers in all fields in biology, health and agro-ecology, where the contribution of the rapidly expanding technologies of digital imaging has become essential. The ambition of these calls is in line with the anticipation of bilateral research funding programs between Europe and Africa in the framework of the Horizon Europe Program.
Multiple scientists from the entire African continent have responded to the calls, covering 8 countries: Senegal, Togo, Nigeria, Ivory Coast, Burkina Faso, Morocco, Uganda and South Africa. Besides, we are very glad that 5 of our nodes (Paris-Centre, Montpellier, Bordeaux, Ile-de-France Sud and Bretagne-Loire) are going to work in the framework of the Africa-France Joint Initiative for Biological Imaging.
Finally, the projects have been selected for the need to access imaging resources in response to key challenges that African researchers are facing. Among them, scientists tackle issues in several topics going from infectious diseases to marine biology, but also cancer research, plant biology and climate change.
Call 1 “External Access”:
Call 2 “Twinning Exchange”:
Congratulations to all the laureates! We are eager to welcome you on our core facilities!
Stay tuned to know more about these project’s unfolding!
High-content screening (HCS) is a technology used in drug discovery and research to analyze cell phenotype. HCS has created new opportunities for studying biological phenomena as it combines high-throughput screening methods with automated microscopy on microplate format. Using automated cell manipulations and microscopy platforms, it is possible to easily screen the effects of selected drugs on the model’s phenotype. This technology, available at France-BioImaging at Montpellier Ressources Imaging (MRI), has been used in a recent study identifying therapeutic drugs for a fatal neurodegenerative disorder, the Giant Axonal Neuropathy (GAN). Benoît Bordignon and Cédric Hassen-Khodja, screening experts at the MRI and co-authors in this recent publication, tell you more about the reasons why the HCS technology was essential!
As mentioned before, High-Content Screening uses automated cell manipulations and automated microscopy platforms to easily visualize the modification of the phenotype. In other words, it allows image acquisitions and analysis of a large number of samples, and collects data of biological parameters of interest directly for statistical analysis. Image acquisition and analysis are done in batches and rapidly, which limit potential bias as the process will be identical from one well to another. A huge advantage that prevents issues and saves time!
Giant axonal neuropathy (GAN) is a fatal neurodegenerative disorder for which there is currently no treatment. Affecting the nervous system, GAN starts in infancy with motor deficits that rapidly evolve toward total loss of ambulation. Using the gan zebrafish model that reproduces the loss of motility as seen in patients, scientists conducted the first pharmacological screening for the GAN pathology. They combined behavioral, in silico, and high-content imaging analyses to identify drugs restoring locomotion, axonal outgrowth, and stabilizing neuromuscular junctions in the gan zebrafish.
This is when imaging becomes essential! To validate at cellular level the last 103 selected hits, they have developed a custom-made High-Content Screening method to check if the phenotype was also restored at the cellular level in gan zebrafish, in particular on neuromuscular junction (NMJ) and axonal function. The postsynaptic nature of the drug’s cellular targets provides direct evidence for the pivotal role the neuromuscular junction holds in the restoration of motility.
The results of this study identify the first drug candidates that can now be integrated in a repositioning approach to fasten therapy for the GAN disease.
Scientists working on this study therefore created an automated image analysis protocol using HCS to quantify neuromuscular junctions’ number/size and measure axon length in treated gan zebrafish. Thus, image data treatment had a central place in this study. And this is just an example! This novel high-content imaging methodology represents a useful automated procedure that can be transferred to other neuromuscular conditions for mechanistic studies and drug screening.
Thanks to Benoît Bordignon and Cédric Hassen-Khodja for providing very helpful insights of the study!
You need HCS or another imaging technology or expertise that France-BioImaging provides? To get open access, please login via Euro-BioImaging website! You just have to choose the technology you want to use, then submit your proposal. All applications will be processed by the Euro-BioImaging Hub in close relation with France-BioImaging. And of course, all scientists regardless of their affiliation, area of expertise or field of activity can benefit from open access services! Users whose projects will be validated by Euro-BioImaging will benefit from a waiver for the access cost on France-BioImaging core facilities (france-bioimaging.org/access)
Lescouzères, L., Hassen‐Khodja, C., Baudot, A., Bordignon, B., & Bomont, P. (2023). A multilevel screening pipeline in zebrafish identifies therapeutic drugs for GAN. EMBO Molecular Medicine, e16267. https://doi.org/10.15252/emmm.202216267
COMULISglobe aims at consolidating and extending a collaborative and innovative network that promotes MultiModal Imaging and analysis across scales (MMI) from biological research to clinical diagnostics. To this aim, they will help bridge the gap between biological and clinical imaging, identify, fund, and showcase novel multimodal pipelines, and develop, evaluate, and publish correlation software through dedicated networking activities. COMULIS have two calls and support schemes open:
1. Global Showcases: This call can fund up to 3 showcase projects (with up to 12k Euros each) that tackle an outstanding biomedical research question using two or more imaging modalities across countries. Eligible expenses are travel costs for lab exchanges, consumables, instrumentation access, supplies, or sample mailing fees. Please send your 2-page applications to andreas.walter@hs-aalen.de by July 23rd, 2023. Projects need to take place between September 1st, 2023 and April, 30th,2025.
Find more info here: https://www.comulis.eu/comulisglobeshowcase-projects
2. Lab Exchanges/Mobility Grants: These lab exchange fellowships are aimed at supporting individual mobility, strengthening the existing networks and fostering collaborations by allowing PhD students, Early Career Investigators (ECIs), facility staff and experienced researchers in the field of MultiModal Imaging to visit an institution, laboratory or industry in another country. The lab exchange will be offered on regular competitive calls throughout the duration of the CZI grant.
Find more info here: https://www.comulis.eu/comulisglobe-lab-exchange
Atomic Force Microscopy (AFM) is a scanning probe microscopy technique that relies on measuring the interaction forces between a sharp tip and the surface of a sample to generate high-resolution images of its surface features and mechanical properties. A very broad range of sample types can be imaged with this technique at a very high resolution – at sub-nanometer level for some of them! Discover the AFM at the Montpellier node of France-BioImaging with Christine Doucet from Integrative Biophysics of Membranes team of the Centre de Biochimie Structurale.
AFM provides images in physiological conditions, in liquid, over a length-scale ranging from few nanometers (single biomolecules) to tens of micrometers (living cells). In fact, the resolution depends on the tip radius and sample properties. For some of them, you can routinely obtain a nanometer lateral resolution and Angstrom axial resolution!
You want a video-rate version of the biological samples you are imaging? The High-Speed AFM, permits the acquisition of movies at approximately 10 images per second, enabling the visualization at nanoscale of dynamic biological processes involving biomolecular interactions, diffusion or conformational changes. It delivers nanometric resolved images typically at the same speed as conventional fluorescence microscopes!
AFM in ambient conditions and in liquids has a key limitation in that it does not directly provide chemical information about the sample being imaged. However, this limitation can be overcome by combining AFM with other techniques to obtain additional information about the sample’s composition.
One commonly used technique in correlation with AFM is fluorescence microscopy. This combined approach of fluorescence labeling and AFM provides valuable insights into the chemical and biological properties of the sample. It was recently used on the Montpellier custom-made correlative AFM / fluorescence setup to observe the sublocalization of proteins in HIV-1 budding sites 1. They also used it to unambiguously attribute some unexpected configurations of the nucleoplasmic sides of Nuclear Pore Complexes 2. In these two cases, fluorescently-labeled proteins were imaged by dSTORM (direct STochastic Optical Reconstruction Microscopy). Of note, the lateral resolution of dSTORM and AFM are both in the 20 nm range with such samples, which makes their combination ideal!
In addition to fluorescence microscopy, AFM can also be correlated with other complementary techniques to obtain chemical information about the sample, such as Raman spectroscopy, Infrared Spectroscopy, X-Ray spectroscopy, microscopy and scattering.
Here are 2 studies where Atomic Force Microscopy were essential:
Combining mechanical and superresolution measurements to reveal the plasticity of the Nuclear Pore Complexes
Nuclear pore complexes (NPCs) are the only gateways between the nucleus and cytoplasm in eukaryotic cells, facilitating the transport of selected cargoes of size from a few up to hundred nanometers. This versatility implies an important pore plasticity. Here, by combining atomic force microscopy (AFM) and single molecule localization microscopy (SMLM), a group led by France-BioImaging R&D team members Christine Doucet and Pierre Emmanuel Milhiet revealed that the NPC basket is very soft and explores a large conformational landscape: apart from its canonical basket shape, it dives into the central pore channel or opens, highlighting how this structure can adapt, and let morphologically diverse cargoes shuttle through NPCs.
Vial et al., Nanoscale, 15, 5756-5770 (2023)
Structural Biology meets Correlative Imaging
Huntington’s disease is a neurodegenerative disorder caused by an extended polyglutamine (poly-Q) tract in huntingtin. Here, using NMR, the team of Pau Bernado (CBS Montpellier) demonstrated that this poly-Q tract adopts long α-helical conformations. By adding correlative Atomic Force Microscopy and Fluorescence Microscopy data obtained in the FranceBioImaging facility PIBBS in Montpellier, they could demonstrate that the stability of this α-helix is a stronger signature than the number of glutamines, in defining the aggregation kinetics and the structure of the resulting fibrils, potentially linked to their pathogenicity.
Elena Real et al., Nature Structural & Molecular Biology, 30, 309–320 (2023)
Atomic Force Microscopy is open to collaborations under Proof-of-concept studies via Euro-BioImaging webportal (www.eurobioimaging.eu/service)! At the Montpellier node of France-BioImaging, you will be in contact with Dr Luca Costa (costa@cbs.cnrs.fr) with whom you will talk about the feasibility and the inherent experimental constraints linked to the technique. The collaboration procedure is discussed on a case-by-case basis, depending on the duration and technicity of the required experiments. Feel free to submit your project!
Thanks to Christine Doucet and Emmanuel Margeat for providing helpful information!
FBI opens a call for the recruitment of its next Deputy Director for International Affairs
Deadline: June 1st, 2023
The Deputy Director for International Affairs will oversee a key strategic mission: develop France-BioImaging’s international activities. This includes enabling France-BioImaging to expand and enhance its engagement in the international community and within targeted communities, with a focus on Europe and Africa. The three primary goals for this position are to increase FBI’s participation in Horizon Europe programme; aid in developing FBI’s approach to international outreach; and build a long-term engagement with FBI’s international partners. The Deputy Director will work closely with the Manager of External Affairs to tailor specific cooperation activities, prepare strategic decision-making and prioritize needs for future international initiatives.
France-BioImaging is a national research infrastructure distributed throughout France that provides researchers with access to the latest innovations in biological imaging and aims to accelerate the transfer of technological and methodological innovations in biological imaging to the 22 platforms that constitute the infrastructure. The Deputy Director for International Affairs will contribute to the development and strengthening of France-Bioimaging international relations and outreach activities.
The Deputy Director for International Affairs will work within the national coordination of the France-BioImaging infrastructure. He/she will work within a team distributed between Montpellier and Bordeaux, composed of 4 people: the Scientific Director and the Deputy Director for International Affairs, the Internal Affairs Manager, and the External Affairs Manager.
Time commitment: 20% of his overall working time
Mandate duration: 5 years
More details and information in the pdf below
Entry into function is planned as soon as possible, September 1st, 2023 at the latest.
If you are interested,
please send a short CV and a motivation letter (2 pages) at direction@france-bioimaging.org
BEFORE the 1st of June
Age-related macular degeneration (AMD) affects more than 150 million people worldwide (early AMD) and 10 million of patients suffer from debilitating late stage AMD. Blurring central vision, this eye disease progresses over time, usually beginning when people are around their 50s or 60s by causing damage to the macula, in the retina. Researchers from the Institut de la Vision (Sorbonne Université, INSERM, CNRS, UMR_S 968) recently published about the AMD. Thanks to Serial Block-Face Scanning Electron Microscopy (SBF-SEM) experiments carried out at the ImagoSeine core facility (Institut Jacques Monod / FBI Paris-Centre node), they describe in this new study melanophages as a disease-progression marker.
Early or intermediate AMD is characterized by pigmentary changes and lipoproteinaceous debris accumulation between the photoreceptors and the melanosome-rich retinal pigment epithelium (RPE) or below the RPE. Later, AMD can be complicated by central choroidal neovascularization or by an expanding lesion of the photoreceptors. Even though patients with early or intermediate AMD can progress and develop late AMD, a large part of patients stay stable for years, underlining the potential usefulness of progress.
AMD is associated with the appearance of hyperreflective foci, with reflectivity comparable to melanocyte-containing RPE cells. Thbs1 and CD47 are both important for the elimination of these cells. In the absence of either of them, melanocyte-containing RPE cells would then accumulate. The goal was to determine the origin of these cells in the retina, and the main question was: are these cells RPE migrating to the wrong place, or melanosome phagocytes cells having ingested melanosomes?
SBF-SEM: the key to answer this question
The Serial Block-Face Scanning Electron Microscopy (SBF-SEM) is a 3D electron microscopy imaging technique, where an ultramicrotome is placed inside a SEM. Biological samples are beforehand stained with heavy metals and embedded in a plastic resin block. Inside the microscope, a thin-section is cut at the surface of the block and discarded. Then, an image of the surface of the block – therefore inside the sample – is made, using back-scattered electrons. The process of cutting and imaging is repeated automatically as many times as necessary to produce a 3D stack of images inside the sample, as it is progressively imaged and destroyed.
This technique allows 3D imaging of large samples for Electron Microscopy standards (up to several hundred microns in each of the X,Y,Z direction) at high resolution. This technique is often used to image whole cells, or even small pieces of tissues in 3D. The two major domains of application are to:
The benefits of bioimaging in this study
In the study, SBF-SEM was essential. As previously mentioned, AMD is associated with the appearance of hyperreflective foci, with reflectivity comparable to melanocyte-containing RPE cells. In the images produced by SBF-SEM, the retinal pigment epithelium (RPE) surrounding the melanophages in mice, where CD47 was inhibited, were markedly less pigmented and deformed compared to those where Thbs1 was blocked. This suggests that melanosomes have been transferred by phagocytosis from the RPE to nearby melanophages because they lack CD47. Finally, authors have shown that CD47 acts as a “don’t eat me” signal. The SBF-SEM was a great addition to this study where understanding the 3D spatial organization of the structure of interest was key.
Thanks to Jean-Marc Verbavatz for providing very helpful insights of the study!
Augustin, S., Lam, M., Lavalette, S. et al. Melanophages give rise to hyperreflective foci in AMD, a disease-progression marker. J Neuroinflammation 20, 28 (2023). https://doi.org/10.1186/s12974-023-02699-9
You need SBF-SEM or another imaging technology or expertise that France-BioImaging provides? To get open access, please login via Euro-BioImaging website! You just have to choose the technology you want to use, then submit your proposal. All applications will be processed by the Euro-BioImaging Hub in close relation with France-BioImaging. And of course, all scientists regardless of their affiliation, area of expertise or field of activity can benefit from open access services! Users whose projects will be validated by Euro-BioImaging will benefit from a waiver for the access cost on France-BioImaging core facilities (https://france-bioimaging.org/access/)
Deadline: April 21th, 2023
The three national infrastructures ProFi, France-BioImaging and FRISBI along with the GIS IBiSA are pleased to announce a call for a funded access to IBiSA-labelled facilities.
Our aim is to promote IBiSA facilities networking through interdisciplinary research projects.
Applications should request access to at least two different IBiSA facilities from two disciplines (structural biology, Biological imaging and proteomics). The call is open to any academic laboratory.
The amount of the financial support will be up to 5000 € per application to cover facility costs.
Applications should be submitted to: Call-IBISA-FBI-FRISBI-PROFI@i2bc.paris-saclay.fr
using the template document https://mycore.core-cloud.net/index.php/s/VNLU2jgfcP4o0NN
The deadline for this inter-infrastructure access call is April 21, 2023.
All submitted proposals will be peer-reviewed by independent experts and the final funding will be approved by a committee comprising 2 representatives from each infrastructure as well as representatives
from GIS IBISA. We advise the project PI to contact the chosen facilities in order to set-up the optimal experimental design.
The second workshop of Holotomography microscopy will be held from April 12th to 14th on the PFIC microscopy facility.
You will test the HT-2H microscope which has more resolution than his bigger brother HT-X1.
The key features are: No label needed, High resolution with one single lens 60X NA 1.2 water immersion (120 nm XY resolution, 356 nm Z resolution, 150 fps T resolution ), quantifiable data, Low phototoxicity, fast imaging.
The microscope has both 3D Holotomograms and 3D fluorescence capabilities in one single unit.
To better prepare your samples for imaging the Tomocube will give us some mounting chambers.
Registrations are mandatory here.