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EquipEx : ImagInEx BioMed

Imagerie innovante d’excellence dans le domaine biomedical : plateforme de criblage à haut-débit et à très haut-contenu

The proposal consists in setting up a new Facility dedicated to the screening and analysis based on functional high content screening microscopy. Although some HCS system are already in place in France, our project is unique in the integration of the techniques, in the confinement zones (S1,S2,S3) where the systems will be located, and the cross-comparison of the results between different fields in order to find different applications for selected hits increasing their value. This will establish a highly competitive Facility at the international level. High content microscopy depends on a variety of techniques aiming at the study, at different scales, of dynamic molecular interactions in living cell either healthy or suffering from physiopathological disorders. This Facility will be supported by the BioImaging Center Lille-Nord de France ( headed by F. Lafont, which holds the local cellular and tissue imaging platforms and expertise in imaging techniques used in biophotonique, atomic force and electron microscopy, and cytometry. The BioImaging Center Lille is supported by the Sciences and high Education Cluster (PRES) Lille-Nord de France (http://www.univ-lille-nord-de-franc...) which include notably the Universities Lille 1 (Science & Technology) and Lille 2 (Medicine), and also by the DRRT [1] , CNRS, INSERM, INRA and ANSES, the “Institut Pasteur de Lille”, The “Région Nord Pas-de-Calais”, the Canceropole, and three industrial clusters (nutrition-health-longevity ; Matériaux et applications pour une utilisation durable ; Aquimer). This is a multi-sites Facility. Because all the scientific partners belong to the PRES, it will be the administrative supervisor of the project. The BioImaging Center Lille has been recognized by the French national organization GIS-IBiSA [2] that gives its label to first ranked R&D facilities also providing services to academics and industrials in several fields including cell imaging. The project proposed for this label application was mainly that presented herein.

Thanks to the arrival in Lille of P Brodin, a worldwide expert in the field and project emerging (F Lafont), we had to acquire HCS equipment. Instead of only buying this equipement, we decided to identify needs of several groups, including leaders in their field (M Chamaillard, F Lejeune, C Locht, JC Michalsky, B Pot, N Prevarskaya, B Staels), to launch an original Facility based on integrated approach and which will fill technological and methodological gaps. The project should also be understood as a taking part of the major effort in the North of France Region towards specific global health problems as the Region will support the activities of candidates for Centers and Laboratories of Excellence (European Genomics Institute for Diabetes), Center of Infection and immunology of Lille ; Metabolomic-Glycoproteomic Laboratory and the University Hospital Institute for personalized Medicine. To extend the valuable expertise in genomics and proteomics in Lille, the Facility will increase the support capacity of the BioImaging Center Lille Nord-de-France to be applied to the biomedical themes developed locally.

One technological cleft is to provide a continuum of techniques allowing, once the first screen is performed, to go towards very high-content screening (HCS) and high-resolution analysis for the selected hits. We want to perform this technological flow in one single Facility to optimize the interactions between the experts involved. Thus, the functional HCS facility will become the core of the BioImaging Center Lille. Technological transfer and high-resolution techniques will be put in the pipeline of the investigations. Another cleft resides in the cross-comparison of the outputs in between scientific projects. By establishing a working group with chemists (B Deprez), biologists of different fields, microscopy experts (L Héliot), biophysicists and biocomputing people, we want to be able once a drug has been validated in one assays (e.g. in cancer) to directly test its efficiency in others (e.g. inflammation, metabolic diseases….). This project will provide an ambitious boost in the scientific themes developed locally. At the national and international level, this multidisciplinary facility will couple the different aspects of research related to the characterization of biomolecules with therapeutic features and the analysis by screening of genes involved in physiopathological disorders. Moreover, the project proposes to set-up a high technology continuum from the dynamic screening to the analysis of selected hits at the nanometer scale of intermolecular interactions at the cell surface. We propose an integrated facility from the screening to the characterization of the functional dynamic molecular interactions, using atomic force microscopy, biophtonic multimodal techniques (FLIM/SLIM, FCCS [3]) to the electron microscopy.

During the first phase (36 months), we aim at having settled the complete facility. Related directly to HCS, the plan is the first year to install systems in S1, S2 and S3 environment, which would be unique in France, and then to go for the transfert of high content analysis module (FLIM and FCCS) the following two years. Some high-resolution systems are currently under test (AFM-PALM [4]) and others would have to be installed rapidly since commercially available (AFM-BioMat, TEM, MEB [5]). Finally, one system will be built, tested and validated in house –the second and third year of this first phase. During the second phase that will end 5 years after the phase 1 the complete corpus of the scientific projects will be achieved. During this second phase, the establishment of specific validated systems will lead to industrial developments especially because some partnerships are already established with manufacturers related to the project. We also envision development towards diagnostics use with the benefit of the local expertise in diabetes (genomics, proteomics, cohorts of patients, drug discovery). The idea thus is to take benefits from our relationships with specific industrial clusters to develop new diagnostic tools and therapeutics drugs.

Based on the transversal management of the BioImaging Center Lille Nord-de-France, the project will be developed on several sites with reinforced synergies thanks to technological transfer and exploitation of the expertise present on each site bringing a multidisciplinary dimension to the global effort. These sites are : the University of Lille 1 (Sciences & Technologies)-Interdisciplinary Research Institute and the Institut Pasteur de Lille campus (High security laboratory, Lille Biology Institute). The management will follow that of the BioImaging Center Lille with a scientific and instrumentation managers plus the increasing value given by the multidisciplinary working group in charge of cross-comparing the data. The technological support of the BioImaging Center will offer expertise in atomic force, biophotonic and electronic microscopy as well as in cytometry (complementary to the screening microscopy technique) with 18 people dedicated to imaging (incl. staff scientists and engineers). In addition, appointment of human resources specifically dedicated to this project is also planed with the support of our regulator authorities. Importantly, 14 research teams are involved in the development of these technologies. For those Teams involved in the project proposed herein, they were evaluated in 2009 by international committees and were all ranked among the top (A+ and A quotes) in France and many of them are placed amongst the top ranked at the international level.

Thanks to this alliance between high-throughput screening, very high-content analysis and supra-resolution, our local experts with leading research teams in their respective field will develop a coherent and competitive resource, unique in France, targeting highly relevant medical and scientific questions in global health. Finally, our project, aiming at the development of HCS as a diagnostic tool, will open new avenues for future developments and possible patents.

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