MICROBIOTA: FROM MICROBIOME TO FUNCTIONS. Atelier «Outils et modèles d étude du microbiote Intestinal» LYONBIOPÔLE/CENS 17 Novembere 2014

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1 MICROBIOTA: FROM MICROBIOME TO FUNCTIONS Atelier «Outils et modèles d étude du microbiote Intestinal» LYONBIOPÔLE/CENS 17 Novembere 2014 Artem Khlebnikov Microbiota The new frontier of biomedicine 2000, Human Genome 2010, Human Microbiome $3,8B investment drove $796B in economic impact 310,000 jobs? Source: Economic impact of the human Genome Project, Battelle Technology, May

2 Next Challenge For every question, a right technology Source: Computational meta'omics for microbial community studies, Segata N et al. Mol Syst Biol 2013;9:666 3 BIOASTER Technology Institute Snapshot The world s first technology institute in infectious diseases and microbiology An open innovation alliance between industry and academic research leaders A unique mission: create disruptive technologies that could radically improve the way people prevent, diagnose and treat microbial-related diseases. A team of experts in life sciences and engineering that conducts crossdisciplinary public-private R&D programs An independent non profit organization that reinvests all its earnings in innovation 4 2

3 Collaborative Approach A comprehensive offer 1 objective 4 targeted areas 5 key assets Solving technology bottlenecks met by industrial partners & SMEs Antimicrobials Vaccines Diagnostics Pre/Probiotics In-house & academic partners scientific expertise Cutting edge technologies Project management Financial leverage Independent meeting place for cross - collaborations 5 Laboratories & Offices A rapid rise PARIS, Institut Pasteur o 600 m 2, (250 m 2 BSL 1 & BSL2 Labs) LYON, Charles Mérieux & La Doua campuses o 820 m2 (390 m2 BSL1 and BSL2 Labs) o Access to the BSL4 Jean Mérieux Lab 2014 BIOASTER 1 o New Facilites in Lyon o 3600 m2 (labs 2200 m2, BSL1, BSL2 and BSL3) o Access to the BSL4 Jean Mérieux Lab Q

4 A New Age of Open Innovation A unique place for collaboration Technology one stop shop Scientific one stop shop Financial one stop shop One point access to technology toolbox 7 technology platforms A highly collaborative and interdisciplinary environment Academic research leaders World class network Expert team combining PhD, MD & PharmD, hundreds of publications and patents Co-investment in R&D projects proposed by partners French government commitment sharing the risk of disruptive innovation Contribution to EU-funded projects 7 Technological Approach For each problem the right combination MULTI-OMICS MULTI-PARAMETRIC DATA INTEGRATION & ANALYSIS The right technology/analysis for each problem faced the development of antimicrobials, vaccines, diagnostics, pre/probiotics PREDICTIVE MODELS 8 4

5 Microbiota Technology focus GENOMICS De novo genome sequencing Targeted/Shotgun Metagenomics TRANSCRIPTOMICS Metatranscriptomics ANIMAL MODELS Controlled rodents MICROBIOTA DATA STORAGE & COMPUTING Multi-parameter data integration PROTEOMICS Top-down & bottom-up proteomics METABOLOMICS Untargeted & targeted metabolomics (fluxomics, lipidomics) 9 Genomics & Transcriptomics TECHNOLOGY APPLICATIONS Genomics & Transcriptomics 454 GS J PGM MiSeq Proton C1 GeneChip System MICROBIAL GENOMICS Small genomes TRANSCRIPTOMICS Qubit DropSense TapeStation Molecular biology 1 Manager 1 Engineer 1 Technician CCIN2P3 StepOne RESOURCES BSL 2 + (100 m 2 ) Biomark ncounter Bioinformatics 3 Engineers Statistics 1 Biostatistician De novo Resequencing Q Assembly/Mapping Variant Calling Variant Annotation Genome annotation Target Metagenomics WGS Q Q Taxonomic annotation Community structure analyses Functional analyses Pathway analyses CONTACT Frederic Reynier, PhD, frederic.reynier@bioaster.org Manager Genomics and Transcriptomics Core facility Phone: +33 (0) / +33 (0) BIOASTER, Domilyon, 321, avenue Jean Jaurès, Lyon Host/ pathogens Q Gene expression analysis Novel transcripts identification Novel isoforms Alternative splice sites Rare transcripts 10 5

6 Animal models & imaging Animal models & imaging Capabilities/Technologies APPLICATIONS Microbiota : Controlled intestinal Malnutrition Obesity Inflammatory Bowel Diseases Q Quantification, virulence, bacterial transformation Infectious diseases mouse models : Nosocomial Infection Zoonosis Q Different Animal models / routes of inoculation: IV IN SC IM Ins: RESOURCES 1 Manager 2Animal Techs, Lyon + 2 Animal Techs, Lyon 1 Engineer, Lyon + 1 Engineer, Lyon BSL2 BSL3 1 Engineer, Paris 1 Animal Tech, Paris CONTACT Andrea Tamellini, DVM, andrea.tamellini@bioaster.org Manager Animal models & imaging Core facility Phone: +33 (0) / +33 (0) BIOASTER, Domilyon, 321 avenue Jean Jaurès, Lyon Q Data storage & high performance computing TECHNOLOGY APPLICATIONS Data storage and high performance computing High throughput analysis Q Machine specific analysis Workflow development Workstation on demand Bioinformatic services RESOURCES 1 Manager Critical services Highly secure computing 1 System Admininistrator, Lyon 1 Support engineer, Lyon 1 Dev. Engineer, Lyon 1 System Administrator, Paris 1 Dev. engineer Paris Q CONTACT Nicolas Sapay, PhD, nicolas.sapay@bioaster.org Support engineer Information technology, bioinformatics & systems biology Phone: +33 (0) / +33 (0) BIOASTER, Domilyon, 321 avenue Jean Jaurès, Lyon 12 6

7 Metabolomics & Proteomics TECHNOLOGY APPLICATIONS Metabolomics & Proteomics Proteomics Partners METABOLOMICS FLUXOMICS Posttranslational Modifications TARGETED UNTARGETED MTA Finger printing Metabolite Profiling LIPIDOMICS Identification RESOURCES 1 Manager PROTEOMICS Quantification Characterization Sample preparation & Automation Proteomics Partners 1 MS Engineer 1 Technician 1 MS lab 1 NMR lab 1 NMR Engineer 1 Bioinformatician Biosafety Environment P2 & P3 (2015) CONTACT Frédéric Béquet, PhD, frederic.bequet@bioaster.org Manager Metabolomics & Proteomics Corefacility Phone: +33 (0) / +33 (0) BIOASTER, ISA, 5 rue de la Doua, Villeurbanne 13 Microbiota profiling Integrated applications in metagenomics, from clinical sample to data analysis Genomics & Transcriptomics Characterized Unknown DNA ISOLATION PROTOCOLS DNA/RNA extraction from stool, blood and saliva samples 16S sample analysis Workflow DATA ANALYSIS 16S sequence data analysis Bioinformatics/statistics specialists Automated pipelines Visualization tools MULTIPLE NGS PLATFORMS 16S sample analysis with MiSeq, PGM or 454 GS FLX COMPUTING INFRASTUCTURE Partnership with CNRS-CCIN2P3 Access to the computer farm and cloud infrastructures Access to the file storage and database clusters DUAL-INDEX SEQUENCING STRATEGY Capable to multiplex up to 384 samples in one MiSeq run 14 7

8 Microbiota profiling Integrated applications in metabolomics, from clinical sample to data analysis Unknown FULLY AUTOMATED SAMPLE PREPARTION Stool, blood samples Characterized Metabolomics Workflow DATA INTEGRATION Metabolite confirmation Structure elucidation Metabolomics & Proteomics GLOBAL METABOLOMICS ANALYTICS NMR,CE-MS,HRMS-MS/MS NMR HRMS MS/MS CE MS Metabolite Profiling Metabolic Fingerprinting COMPUTING INFRASTUCTURE Partnership with CNRS-CCIN2P3 Access to the computer farm and cloud infrastructures Access to the file storage and database clusters DATA ANALYSIS State of the art chemometric tools in house development & analysts Visualization tools 15 PROJECT Controlled Microbiota Lactobacilli probiotic validation Immune system Gut interface Metabolism Probiotic to evaluate NUTRITION INTESTINAL MICROBIOME PROBIOTICS Develop a controlled murine model Provide experimental evidence underlying allegations for the use of Lactobacilli probiotic for nutritional intervention to promote juvenile growth in population at risk of protein malnutrition Reproduction Life Science Company Standard Microbiota Germ free Controlled Microbiota Status: Execution 16 8

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