ACCESS Geneva was establish in December 2015 at the University of Geneva in the Biochemistry department within the ACCESS framework of the NCCR Chemical Biology. The facility provides state-of-the-art equipment, technology and methodology for image-based screening (High Content Screening – HCS) and high-throughput screening (HTS). Our goal is to provide infrastructure and know-how support to screening projects from Swiss academia or industry.
Image-based screening allow the precise identification and quantification of very diverse phenotypes from most of current biological models. Screening projects involves, several types of models perturbations such as RNA interference, small molecules or mutations, to study very diverse biological processes. The technology allow then a very fast and robust identification of unpredicted phenotypes.
At ACCESS Geneva, we provide a complete solution to scientists interested in pursuing HCS projects with advice on experimental design, one-to-one training and a strong guidance every step of the way, from assay development to data acquisition and data analysis. The platform expertise is based on a long experience in systems biology and high-throughput screening technology. Moreover, we constantly leverage our efforts toward new directions and development in the field.
The facility also supports postgraduate training via formal workshops and seminars.
We are fully equipped to run any high-throughput project. Our premices offer full support from assay designing to image and data analysis.
Experimental design and procedure
The assays and the samples can be run and prepared at the facility, using our dedicated tools: Agilent Bravo® liquid dispenser (compound printing), Multidrop reagent/cell automated dispenser, sterile hood, incubator, automated pipettes, plate washer (Biotek EL406®).
|Cell culture room: ACCESS Geneva is equipped with all tools needed for your cell-based experiment in a P2 lab. You will have access to a sterile cell culture hood, incubator, cell-counter, centrifuge (for plate and tubes), micropipettes, fridge/freezer, consumable plastic and liquid (excepted culture media).
|We have recently acquired a FACS cell sorter Sony SH800, equipped with 4 collinear lasers and 6 detectors, 2-way or plate sorting (6- to 96-well). It is enclosed in a P2 sterile hood. The SH800 allows sorting of a wide range of cell sizes using the 70 μm, 100 μm and 130 μm microfluidics sorting chips. This is the ideal tool for any clone sorting. Its usage can be combined with our automated microscope to be very rapidly able to check the quality of sorted clones or cell populations. More info about this equipment
To allow extremely rapid and precise dispensing of micro-volume of compound, we use the Agilent Bravo® liquid handler (Compound printing in assay plate). The robot is enclosed behind a Plexiglas shield to avoid any contamination of the sample. New dispensing methods can be programmed and tested extremely rapidly. The pipetting head is using disposable tips to avoid any cross-contamination.
A Multidrop Combi® is available to dispense very precisely reagents or cell suspensions in assay plates. The automatisation of cell dispension is a mandatory feature for any screening project.
A Plate washer Biotek EL406® is used for sample preparation, antibody dispensing and sample washing. This is the mandatory tool to stain the sample in 96- or 384-well plates. This washer allows very robust and consistent preparations of the sample which is of crucial importance for a screening project.
Within our premices, we offer an automated microscope Molecular Devices™ IXM-XL®, which allows acquisition of thousands of images per hour, in different colors or magnification.
The PRIMO® Photopatterning sytem is an optical system, directly docked on an inverted microscope, allows to project patterns of UV-light with very high resolution (1 μm). The UV-light, shaped on demand, can be used for multiple purposes, among them, micropatterning of biomolecules (ECM proteins, antibodies…), photolithography of UV-curable resins, or precise photopolymerization of hydrogels. Any labware (including 96/384 well plate) and surface can be used for those application. The micropattern can be coated with one or more biomolecules in an homogenous way or with gradient.
ACCESS Geneva provides all aspects of data storage, archive, back-up and analysis resource for scientists.
|We use Molecular Devices™ ImageXpress Micro XL®, an automated microscope, with bright field, led light source, 5 fluorescence cubes, 8 objectives, for fixed or live imaging, and Z-stack capacity. This microscope allows the user to acquire a large amount of high quality images. It can handle any type of culture plates, but the facility recommends a specific one which has been tested and fully set up on the instrument. It has a fast connection to our remote server to allow image transfer and storage on a secured support. After a short training on the acquisition software, any user should be rapidly independent. Originally dedicated to screening projects this tool has become now more widely used for every day experiment which involves several test conditions.|
|We’ve recently purchased and installed the latest automated microscope from Molecular Devices™. The ImageXpress Micro Confocal® is a spinning disc microscope, with 7 colors, 5 objectives (4X to 60X) and the latest sCMOS camera. This new microscope acquire very sharp images in a very fast mode. New applications from our previous system can be considered, like fast live or Z scan of 3D objects. The microscope can scan any kind of imaging pates (24, 96, 384 well), but also regular slide. The microscope is connected to our database, making the data available from anywhere through our 5 virtual machines.
|ACCESS Geneva is also equipped with a full mode plate reader Biotek™ Synergy™ H1, enclosed in a temperature controlled cabinet, and linked to a robotic arm for screening plate feeding. The reader is also equipped with two syringes for direct injection of reagent in the test plate.|
In order to facilitate the data storage and analysis to all users, the facility has developed a fully integrated data management system, based on Molecular DevicesTM software environment. All data generated are automatically saved on a secured server, and are easily accessible at any time with no risk of data or metadata lose. Thanks to the installation of dedicated virtual machines, any user can access his data at any time using a direct or VPN connection to the UNIGE network.
|We offer MetaXpress™ Custom Module Editor, a deep image analysis tool, available on the virtual machine. The latest version of MetaXpress analysis software allow the user to develop very complex analysis pipeline. By implementing several segmentation steps, users can fully dissect any image. More than fifty parameters can then be extracted for each mask in each detection channel, which represents more than 200 data points per cell. Overall, this provides a precise phenotypic description of the image. The intensive analysis job is then sent to our calculation server, equipped with PowerCore®, which is able to provide multi-thread processing.
|The large amount of data generated by a complex phenotypic analysis is not easy to handle and requires an appropriate data analysis software. For this purpose, we have installed AcuityXpress®, which helps the user, to annotate their plate, plot the data and run statistical analysis. A full support and software training is provided to cope with the large and complex data set generated.|
To discuss about your project or get information on the facility, fees and prices:
Please contact Dr. Dimitri Moreau, Head of ACCESS Geneva. Tel. 00 41 (0)22 379 61 96.
Special fee policy are applied to the NCCR Chemical Biology labs.
Our sound expertise is validated by a number of published screening work. Below are some relevant examples.
- López-Jiménez A.T., Cardenal-Muñoz E., Leuba F., Gerstenmaier L., Barisch C., Hagedorn M., King J.S., Soldati T., “The ESCRT and autophagy machineries cooperate to repair ESX-1-dependent damage at the Mycobacterium-containing vacuole but have opposite impact on containing the infection“, PLoS Pathog., 14(12):e1007501, doi: 10.1371/journal.ppat.1007501, 2018.
- Vacca F., Vossio S., Mercier V., Moreau D., Johnson S., Scott C.C., Paz Montoya J., Moniatte M., Gruenberg J., “Cyclodextrin triggers MCOLN1-dependent endo-lysosome secretion in Niemann-Pick type C cells“, J. Lipid Res., pii: jlr.M089979, doi: 10.1194/jlr.M089979, 2019.
- Banach-Orłowska M., Jastrzębski K., Cendrowski J., Maksymowicz M., Wojciechowska K., Korostyński M., Moreau D., Gruenberg J., Miaczynska M., “The topology of lymphotoxin &[beta] receptor (LT&[beta]R) accumulated upon endolysosomal dysfunction dictates the NF-&[kappa]B signaling outcome“, Journal of Cell Science, 2018.
- Eren R. O., Kopelyanskiy D., Moreau D., Chapalay J. B., Chambon M., Turcatti G., Lye L.-F., Beverley S. M., Fasel N., “Development of a semi-automated image-based high-throughput drug screening system“, Frontiers in bioscience (Elite edition), 10, 242-253, 2018.
- Moreau D., Gruenberg J., “Automated Microscopy and High Content Screens (Phenotypic Screens) in Academia Labs“, Chimia, Vol. 70, Number 12, December 2016, pp. 878-882(5).
- Wu K.X., Phuektes P., Kumar P., Yen Lin Goh G., Moreau D., Tak Kwong Chow V., Bard F., Jang Hann Chu J., “Human genome-wide RNAi screen reveals host factors required for enterovirus 71 replication“, Nature Communications, 2016.
- Wong H.H., Kumar P., Tay F.P., Moreau D., Liu D.X., Bard F., “Genome-wide screen reveals VCP requirement for coronavirus exit from endosomes“, Journal of Virology, 2015, 89(21):11116-28.
- Kumar P., Goh G., Wongphayak S., Moreau D., Bard F., “ScreenSifter: analysis and visualization of RNAi screening data“, BMC Bioinformatics, 2013, 14(1):290.
- Moreau D., Bard F., “Comprendre et combattre les toxines A/B en décryptant leur transport intracellulaire“, Medecine/sciences, 2012, 28, 1, 28-31.
- Moreau D., Scott C., Gruenberg J., “A Novel Strategy to Identify Drugs that Interfere with Endosomal Lipids“, CHIMIA International Journal for Chemistry, 2011, 65, 846-848.
- Moreau D., Kumar P., Wang S.C., Chaumet A., Chew S.Y., Chevalley H., Bard F., “Genome-wide RNAi screens identify genes required for Ricin and PE intoxications“, Developmental Cell, 2011, 21, 2, 231-244.
- Chia N.Y., Chan Y.S., Feng B., Lu X., Orlov Y.L., Moreau D., Kumar P., Jiang J., Soh B.S., Huss M., Kraus P., Lufkin T., Lim B., Clarke N., Bard F., Ng. H.H., “A genome-wide RNAi screen reveals determinants of human embryonic stem cell identity“, Nature, 2010, 468, 316-320.