Antonio Del Casale. Microbion srl Verona University Spin-off - Italy
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1 Antonio Del Casale Microbion srl Verona University Spin-off - Italy Food Matters Live 19 November 2014
2 Microbion Verona University Spin-off Biodiversity services & products Finds the best performing microbes using innovative DNA-fingerprinting
3 Microbion Verona University Spin-off Technology Transfer Established company in 2011 >200 peer-review research publications >50 Successful industrial case-studies >20 Customers >6 Industrial sectors
4 Microbion Verona University Spin-off What we do? Service provider: Analytical services R&D services Bio-bank service Products developer: Molecular diagnostics Pro-tech microbial strains
5 Microbion Verona University Spin-off What customers need? Innovation: Product development Process optimization Quality control: Safety assessments Regulatory compliance
6 Microbes Biodiversity Microbes: Smallest & most abundant living organisms Biodiversity Who is the good? Can the good s win?
7 Microbes Biodiversity Pro-technologic Make products Health improver Pathogenic Harmful Spoiling Unwanted Anti-pro
8 Microbes Biodiversity Natural occurring microbes Pro-technologic Make products Health improver Industrial microbes - Manufactured - Controlled Food Fermented Health Probiotics Agriculture Bio-fertilisers Bio-pesticides Green Chemistry Bio-fuels Bio-plastics Bio-preservatives
9 Food Microbes Industrial microbes Bacteria (Lactic Acid Bacteria) Yeast (Saccharomyces spp.) +Raw ingredients Benefits: Shelf-life Taste/Flavour Digestibility Nutrition
10 Health Microbes Industrial microbes Bacteria (Lactic Acid Bacteria) Yeast (Saccharomyces spp.) Probiotics Benefit: Competition to pathogens Wellness & Nutrition Immuno-regulator Psychotropics Human Microbiome Top 10 emerging technologies The World Economic Forum (1 September 2014)
11 Health Microbes
12 Advantages of the molecular approach DNA patters Molecular markers Signature sequences Genomes sequence Meta-genomic High discrimination High accuracy High reliability...and OVER the species level
13 Advantages of the molecular approach Intra-specie biodiversity: Same specie Different abilities DNA patters Molecular markers Signature sequences Genomes sequence Meta-genomic High discrimination High accuracy High reliability...and OVER the species level
14 Genre Advantages of the molecular approach STRAIN Specie DNA patters Molecular markers Signature sequences Genomes sequence Meta-genomic Saccharomyces cerevisiae (strain?)
15 Case study: Innovation in traditional winemaking Improved quality wines Cost efficiency Local population study (1000+ yeasts) MASI Yeast Bio-Bank (100+ yeasts) Experimental wine production (10+ yeasts) Scale-up winemaking (2 yeasts) Distinctive flavour Cost saving (and C0 2 ) Seasonal consistency Unique on the market!
16 Genere Case study: Microbes manufacturing Improved quality control Regulatory compliance Patent deposit Intra-specie biodiversity study Strain? Species Molecular Fingerprinting Services Manufacturing: Batch validation Regulatory: Genome stability reference Legal: IP right defensibility
17 Advantages of the molecular approach genus strain species Consumer confusion by intra-species diversity: S. cerevisiae pathogenic, when adapted to human niche (temperature) Enterococcus faecium health promoter or marker for water pollution? Feed additive Bacillus cereus Vs. hemotoxic B. cereus Probiotic Escherichia coli (Nissle 1917) Vs. virulent E. coli
18 Genome analysis Random genome sampling Random Amplified Polymorphic DNA (RAPD-PCR) Whole genome profiling Pulsed Field Gel Electrophoresis (PFGE) Rapid Not unambiguous Unambiguous Time consuming
19 Genome analysis Recent advancement of PFGE methodology: Optical Mapping Linearized genome Genome restriction Fragments detection and measuring Strain specific DNA-barcode Strain tracking Detection of genomic rearrangement Genome sequencing scaffolding
20 Genome analysis Strain specific DNA-barcode Genome sequencing scaffolding L. brevis ATCC 367 (NC ) (in-silico WGM) L. brevis KB290 (NC ) (in-silico WGM) L. brevis ATCC 367 (NC ) (in-silico WGM) L. brevis LMG (4 independent replicates)
21 Genome analysis Genomic DNA restriction fragment (PFGE, ribotyping) Profiling PCR-amplified DNA (RAPD-, ERIC-, REP-PCR) PCR-amplification of restriction fragments (AFLP) Restriction analysis of DNA fragments (PCR-RFLP) DNA Multi-Locus Sequence Typing (MLST) House-keeping Multi-Locus Sequence Analysis (MLSA) Amplified Ribosomal DNA Restriction Analysis (ARDRA) rrna gene sequencing analysis (SSU, LSU) Genomic DNA-DNA Hybridisation (DDH) Genomic DNA mol% G+C Whole genome sequencing analysis
22 Genome analysis Tremendous advancement of DNA sequencing = Next Generation Sequencing Reduced time and lower cost Improved downstream analysis Regulatory authorities suggest or require state-of-the-art-technology = genome sequencing: FDA Guidance for Industry: Early Clinical Trials with Live Biotherapeutic Products: Chemistry, Manufacturing, and Control Information Strain-specific diagnostics and tracking EFSA Guidance on the safety assessment of Enterococcus faecium in animal nutrition Safety assessment
23 Genome analysis All molecular markers become available (also currently unknown) development of specific diagnostic methods Gene copy number and regulators of health claims relevant genes Adaptation to the intestinal niche Genes involved in the interactions with the host Probiotic factors (e.g. serpin) able to suppress inflammatory responses Antimicrobial compounds for pathogen inhibition Assessment of health risks Biogenic amine production Virulence genes Antibiotic-resistance gene
24 Genome analysis Antibiotic-resistant strains Comparative Genomics the study of the relationship of genome structure and function across different biological species or strains (EFSA, 2012)
25 Team Antonio Del Casale CEO MSc Biotechnology Tech Transfer Open Innovation Fabio Fracchetti COO PhD Biotechnology Molecular Microbiology Patents Valter Carturo CFO MEc Business Administration Chattered Accountant Start-up Operations Sandra Torriani Scientific Adv. Full Professor Microbiology Food-tech Innovation 150+ Peer review publications Giovanna Felis Scientific Adv. Associate Professor Microbiology Lactic Acid Bacteria Taxonomy & Genomics
26 The leading microbiology innovation provider (micro-organisms making mega-impact) Antonio Del Casale Meet us at:
27 Milestones & Use of funds Seed 10K Spin-off First 10K customer Veneto Region grant First commercial partner First EU-H2020 project First strain licensed University grants First tech partner First conference invitation Impresa per Impresa ConfindustriaProgramme First patent First patent licensed Spin-out from University facilities Second patent licensed Royalties > Sales Marketing team Second patent SME Instrument EU-H2020 project Third patent Microbion Agro Microbion Health Microbion Food-tech Microbion Energy
28 Golden standards for identification: Multi-locus sequence typing Within a species, ribosomal subunit are not discriminant Actinobacteridae putative proteomes All vs All BLASTp In-silico selection One copy in every genome Dinucleotide frequencies, GC content and codon usage consistent with genome Core genes of Bifidobacteria 18 High resolution between species Discriminate strains of same species 7 Molecular markers typing scheme (Ventura et al. 2006) 9 Candidate markers analysis (partial sequences) Vitafoods Europe 2013
29 ROI Strategy Potential acquisition paths: A Management buy-back B Partial asset sale C Diagnostic brand co-development Lactic Acid Bacteria ID Yeasts ID Acquisition examples benchmark: Lumora Cambridge Spin-off R&D of BART tech raised $2.1M by Tate&Lyle now licensed to 3M
30 ROI Strategy Potential acquisition paths: A Management buy-back B Partial asset sale Diagnostics patents Microbial Strains Acquisition examples benchmark: BioFire sold FilmArray asset to biomérieux s for $450M BioGaia receive 10M/year for L. reuteri from Nestlé infant nutrition
31 Key Advantages Service and Products 20+ Customers success cases 6 Industries Unique advantage: 2013 Sales 50+ collective years of experience Market needs & solutions Unique microbes bio-bank Non-patented trade secrets Open innovation network Consumer products Agri-food Dairy Wine Universities Probiotics
32 Key partners Business Scouting Institutional
33 Genome analysis Definition of Species: Group of strains sharing high level of genomic and phenotypic similarity Foundations for microbial characterization Exchange of information among scientific community Laws regulations and guidelines FDA Generally Regarded As Safe (GRAS) EFSA Qualified presumption of safety (QPS)
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