Accelerating research through access to technology platforms Meeting of the Institut Pasteur International Network American Region – July 3, 2019 1 | C2RT/C2RA – RIIP-America – July 3, 2019
Progress in science depends on new techniques, new discoveries and new ideas, probably in that order. Sidney Brenner 2 | C2RT/C2RA – RIIP-America – July 3, 2019
Progress in science depends on new techniques, new discoveries and new ideas, probably in that order. Sidney Brenner Core Facilities 3 | C2RT/C2RA – RIIP-America – July 3, 2019
Outline • Organization of the core facilities and technology offer at Institut Pasteur, Paris • How to improve technology networking within the Institut Pasteur International Network? 4 | C2RT/C2RA – RIIP-America – July 3, 2019
Progress in science depends on new techniques, new discoveries and new ideas, probably in that order. Sidney Brenner Core Facilities Center for Technological Resources and Research (C2RT) Center for Animal Resources and Research (C2RA) Units for Technology and Services (4) Technology Platforms (13 + 2) 5 | C2RT/C2RA – RIIP-America – July 3, 2019
Missions of the C2RT and C2RA Research Resources • • Next generation of equipment and Structuration and organization of the methods facilities, upgrade of instruments • • Interactions with institutes of technology, Advanced technology and animal engineering schools, and industry partners resources for biological research • • Services at the highest level (speed and Collaborations between research units and facilities quality) • • Technology watch User input and satisfaction • • Support of innovation Proper recognition of personnel in facilities Dissemination • Training in technologies • High level network of infrastructures and core facilities within the IPIN and beyond 6 | C2RT/C2RA – RIIP-America – July 3, 2019
The C2RT and C2RA 209 employees (90% IP) 14 Scientists 79 Engineers 56 Technicians 23 Zootechnicians 6 Postdocs 5 PhD students 11 Trainees 8 Cadres administratifs 7 Assistants Center for Technological Resources and Research (C. d’ Enfert/A. Kehres) PAD (A. Kehres) Center for Animal Resources and Research ( C. Joubert ) 7 | C2RT/C2RA – RIIP-America – July 3, 2019
Structures of the C2RT and C2RA Genomics Proteomics Flow cytometry Multiscale imaging (light – cryo) Nanobody discovery Protein production Molecular Biophysics and Structural Biology Center for Technological Screening Resources and Research Microfluidics (C. d’ Enfert/A. Kehres) and organ-on-chips PAD (A. Kehres) Animal research Center for Animal Genome engineering Resources and Research Parasite production ( C. Joubert ) 8 | C2RT/C2RA – RIIP-America – July 3, 2019
Recent technology advances at the C2RT and C2RA • Long-read sequencing (PacBio, Nanopore) • Light-sheet imaging • High-content screening • Correlated light and eletron microscopy (CLEM) pipelines • Cryo-EM • MaMuT: handling of large, multi-view, multi-modality images • Sorting of nanoparticles • Experimentation under hypoxia • Single cell pipelines • Automation and miniaturization (Ab identification and protein production) • Quality assesment and optimization of protein samples • Analytical centrifugation • Organ-on-chip • Germ-free and gnbotobiotic mice (oligo-MM12) • Mouse/rat models using CRISPR-cas9 technology • Anopheles mass production 9 | C2RT/C2RA – RIIP-America – July 3, 2019
High-throughput sequencing: Increasing autonomous access Shared room (Biomics / IP users) Users Benefits - Free training (MOOCs + IRL) - Simple booking (PPMS) Trained user 243 (28 in 2019) 47 (24 in 2019) - Per-use invoicing - Project accelerator 900 800 Biomics Benefits 700 Utilization 600 (hours) - Contributes to the maintenance contracts 500 - Reduces workload 400 300 a. 62 projects in autonomy in 2019* 200 - Response to criticism on the process duration 100 - Saves time on complex projects 0 janv-19 f é vr-19 mars-19 avr-19 mai-19 juin-19 *estimation based on sequencing runs Biomics IP users 10 | C2RT/C2RA – RIIP-America – July 3, 2019
Exploring biology at different resolutions Viruses Atoms Tissue Cells Proteins Small molecules CONTEXT Light Microscopy Super Res Fluorescence Microscopy Cryo-electron tomography Single Particle cryo-TEM Mass-spec NMR X-ray crystallography (XRD) Structure size 1 mm 100 µ m 10 µ m 1 µ m 100 nm 10 nm 1 nm 1 Å RESOLUTION 11 | C2RT/C2RA – RIIP-America – July 3, 2019
The time for « single particles » is now 90 ’ s huge, highly symmetric helical Massive, highly symmetric Cryo-EM maturation Large, asymmetric 52kD 3.2 Å small, low symmetric 10 ’ s Intermediate, symmetric 12 | C2RT/C2RA – RIIP-America – July 3, 2019
Understanding function inside native environment SPA Dock Into Cell Subtomogram Averaging native COPI coat structure Images and Movie from Bykov et al., eLife 2017 13 | C2RT/C2RA – RIIP-America – July 3, 2019
A building dedicated to cryo-EM • Acquisition of 4 cryo-electron microscopes including Titan Krios allowing single particle imaging and cell tomography • A dedicated building • Hiring of two PIs (D. Hanein, N. Volkmann) and creation of a dedicated core facility • An investment budget of ~15 M € Aquilos Vitrobot Titan Krios G3 financed by Institut Pasteur, the Investment for the future Program (Equipex Cacsice) and public generosity Sample preparation for imaging of single particles Sample preparation for cellular imaging HR SC Glacios Cellular imaging and high resolution imaging of single particles High resolution imaging of Sample screening/Training single particles 14 | C2RT/C2RA – RIIP-America – July 3, 2019
The Biomaterials & Microfluidics core facility Organ-on-Chip Bioengineering Services Technology 1. Microfabrication 2. Custom Chips Gentile et al. 2014 4. HTS/ 3D cell culture 3. Cell confinement … Ranga et al. 2014 emulate™ Gut -on-Chip Yennek et al. 2014 MeningoChip Future Services / Developments 3. Complex Patterning 1.Organoids 2. Disease-on-Chip 15 | C2RT/C2RA – RIIP-America – July 3, 2019
Strategic plan 2019-2023: Provide a favorable technological environment • Expand our nanoimaging initiative by acquiring additional electron microscopes to optimize our use of the Titan KriosTM for atomic resolution in vitro or in cellulo protein imaging. • Develop optical imaging methods for the multi-scale study of host-pathogen interactions : light sheet fluorescence microscopy, planar/cross-sectional imaging microscopy, magnetic resonance imaging, super-resolution microscopy, etc. • Optimize our crystallography, nuclear magnetic resonance (NMR), hydrogen exchange mass spectrometry and biophysics facilities to strengthen our expertise in structural biology . • Set up a metabolomics platform and/ or research unit to provide a shared infrastructure and pool our expertise in sample preparation and analysis using mass spectrometry and NMR. • Develop new single-cell analysis pipelines for transcriptomes, proteomes, metabolomes and other components of the host and microbes. Establish a new infrastructure for simultaneous analysis of the host, the vector and • the pathogen under biosafety level 3 containment conditions (animal facility, insectarium, imaging capabilities). • Boost our ability to identify novel diagnostic and therapeutic solutions : high-content imaging, organ-on-a-chip, microfluidics, miniaturization, point-of-care testing, etc. • Develop high-throughput approaches for antibody identification and production . 16 | C2RT/C2RA – RIIP-America – July 3, 2019
Developments for 2020 • Creation of a metabolomics core facility • Creation of a humanized mice core facility • Reinforcement of our screening capabilities 17 | C2RT/C2RA – RIIP-America – July 3, 2019
Scientific animation and contribution to training • Open Desks (PBI/HAI; Protein-pole) • User training (MOOCs) • Technology Seminars • Technology Workshops • Pasteur Courses • Advanced Imunology, Genome analysis, Protein biochemistry, Mouse Genetics, Fluorescence microscopy ,… • Pasteur network • Licence, Master,… • Continuous education • Host facility for European Core Facility Management University Diploma • CTLS workshops: Building a succesful carreer in a Core Facility 18 | C2RT/C2RA – RIIP-America – July 3, 2019
Outline • Organization of the core facilities and technology offer at Institut Pasteur, Paris • How to improve technology networking within the Institut Pasteur International Network? 19 | C2RT/C2RA – RIIP-America – July 3, 2019
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