Luigi Ravagnan, Head of international affairs

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CBM the Friuli Venezia Giulia Technology
District an introduction
The Italian system meets in Szeged Italian
Institute, Szeged September 25th, 2008

• Luigi Ravagnan, Head of international affairs
• Elia Stupka, Head of Bioinformatics

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The Technology District of the Friuli Venezia
Giulia Region

• WHEN
• October 2004 Framework Agreement between the
  Italian Ministry of Education, University and
  Research and the Regional Government - creation
  of the Technology District of Molecular
  Biomedicine of the Friuli Venezia Giulia Region.
• WHAT
• The Technology District is a geographic area with
  specific economic and social features. Various
  entities join it in order to strengthen research
  and development in the field of molecular
  medicine they also aim at fostering the creation
  and settling down of new entrepreneurship.
• WHO
• CBM Scrl (an SME) has been appointed for setting
  up the development policy of the District. CBM
  also coordinates the Districts activities by
  planning study and research projects as well as
  by fostering new high-tech entrepreneurship

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Mission

• Accelerate the process bringing Research to
  Market (drug discovery, diagnostic a/o
  therapeutic systems)
• Strengthen the interaction and the collaboration
  between public and private sectors
• Support the creation and the development of new
  ventures and valorization of IP/know-how
• Valorize human resources and attract talents
• Establish efficient networks among universities,
  research centers, hospitals, private sector,
  finance and VC, governmental institutions across
  Alpe Adria region

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Consortium shareholders

• PUBLIC SHAREHOLDERS
• AREA Science Park, IRCCS CRO Aviano (Oncology
  Reference Centre), IRCCS Burlo Garofolo Hospital,
  SISSA (International School for Advanced
  Studies), University of Trieste, University of
  Udine, CIB (University Consortium for
  Biotechnologies).
• PRIVATE SHAREHOLDERS
• Assicurazioni Generali SpA, Bracco Imaging SpA,
  Bruker Biospin Srl, Eurospital SpA, Fondazione
  Callerio Onlus, Fondo per lo Studio delle
  Malattie del Fegato Onlus, Friulia SpA, Italtbs
  SpA, Laboratori Diaco Biomedicali SpA,
  Instrumentation Laboratory SpA, Transactiva Srl.

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Human Resources _at_ CBM
42 people, 10 nationalities
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CBM Activities
CBM operates over three fields

• Research Service network
• Competitiveness network
• Knowledge network

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1. Research Service Network

• Technology Platforms with state-of-the-art
  instrumentation available for shared use to
  research centres and companies operating on
  fundamental and applied research.
• Technology Platforms are set up through effective
  collaboration between public and private bodies.
• Highly-qualified staff is available in each
  technology platform.

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1. Research Service Network -Core facilities

• Proteomics and Farmacogenomics
• Genomics
• Bioinformatics
• Optical Imaging
• NMR
• Nano Diagnostics and Analysis

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2. Competitiveness network

• Grants writing and management
• Business Development
• Economic Observatory
• IP Office (in cooperation with AREA Science Park)

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3. Knowledge network
Staff training in the fields of advanced research
and technology transfer

• Training Courses Aimed at strengthening
  technical and managerial know-how in the
  biomedical sector
• Summer School
• Multidisciplinary training activities in the
  fields of molecular biomedicine
• Ingoing and Outgoing Mobility Fellowships
  
• Promotion of advanced training in the sectors of
  biomedicine through the financing of ingoing and
  outgoing mobility fellowships for young
  researchers
• Workshops Events designed for the
  scientific community as well as for a
  non-specialised public

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Coordination activities

• National Committee for Biosecurity, Biotechnology
  and Life Science
• Network of Italian Technology clusters in Life
  Science
• Innovative Medicine Initiative
• ADITE (association of clusters)

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Basovizza Campus today
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Basovizza Campus in the near future
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Core facilities

• Proteomics and Farmacogenomics (CRO Aviano)
  
• Proteomic analysis as well as pre-clinical and
  clinical development of new drugs for
  personalized medicine.
• Genomics (CBM) in collaboration with
  Burlo and SISSA
• Analysis of gene expression and genotyping for
  the comparison of expression profiling between
  healthy and diseased tissues as well as for the
  identification of molecules which act as tumoral
  and genetic markers. Telethon National Genomics
  Service certified.
• Illumina Expression Profiling Service Certified.
• Illumina BeadArray, Affymetrix GeneChip, Taqman
  and Combimatrix platforms for genome wide
  analysis as well as Roche 454FLX and Illumina
  Solexa for deep-sequencing/resequencing are
  accessible through CBM facilities.
• Bioinformatics (CBM)
• Analysis of complexe biomedical data deriving
  from advanced genomics and proteomics
  technologies, with a special focus on customized
  solutions.
• 300GFlops, 7TB storage, DB server, 6
  bioinformaticians

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Genomics Lab

• The CBM, IRCCS-Burlo Garofolo, SISSA team boasts
• a long-term experience in SNPs (single nucleotide
  
• polymorphisms) genotyping.
• The use of at least three different technology
  platforms (Taqman, Illumina, Affymetrix) enables
  CBM to provide services specifically targeted to
  customer needs these range from processing a few
  samples for a small number of polymorphisms to a
  big amount of samples and/or polymorphisms.
• a) A wide range of Affymetrix GeneChip Mapping
  arrays, covering from 10,000 to one million SNPs
  in humans and in many other species
• b) The Illumina system, able to analyze from 96
  to 1536-plex custom SNPs, as well as
  high-density arrays (up to one million SNPs)
• c) Analysis of a reduced number of polymorphisms
  (even single ones) with Taqman technology
• These technology platforms can be used for
  association, linkage and case-control studies as
  well as in molecular karyotyping, identification
  of copy number variations, studies in the field
  of pharmacogenetics, etc.

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Bioinformatics Lab _at_ CBM
Research Service

• Design of custom arrays (Combimatrix and
  Nimblegen tech.)
• Analysis of expression profiling data
• Consultancies in Functional Genomics
• Expertise on handling, analysis and expression
  profiling from archive tissues
• Expertise in the analysis of non-coding elements
  of the genome, such as
• microRNAs
• Non-coding RNAs
• Enhancers
• Insulators
• Verification of large-scale experiments by
  Real-Time, cell-based assays, etc.
• Consultancies for data management, organization
  and analysis
• ERP, LIMS, Web-based services
• Services to health IT companies

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Bioinformatics - Results

• Healthy publication performance, five papers
  papers published in leading international
  journals in less than a year involving the
  facility
• Genome Research, July 2007 (IF 10.25)
• EMBO J, September, 2007 (IF 8.1)
• Nucleic Acids Research, 2008 (IF 6.3)
• Journal of Investigative Dermatology, 2008 (IF
  4.5)
• Genome Research, in press (IF 10.25)
• Ongoing projects and collaborations
• European FP6 Transcode Project coordinated by
  CBM, concluded in March 2008
• FP7 Health in negotiation phase,
  collaboration between SISSA, CBM and
  international partners
• FP7 People / IAPP in negotiation phase,
  collaboration between Wien, Gottingen, CBM and UK
  
• Several FP7 projects still pending involving the
  facility RoK project

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Core Facilities (2)

• Molecular Imaging (CBM)
  in collaboration with Bracco
• Studies aimed at visualizing molecular and
  cellular in-vitro and in-vivo processes both for
  the understanding of biological and pathological
  events within the organism, and for the
  development of innovative therapeutic approaches
  at a molecular level.
• NMR (CBM) in collaboration
  with Bruker and Bracco
• High resolution analysis of liquid and
  semiliquid (tissues) samples by means of NMR
  spectroscopy aimed at metabolomic studies.
• Nano Diagnostics and Analysis (CBM) in
  collaboration with
• SISSA,
  Sincrotrone TS, CNR-TASC
• Development of technologies for the
  manipulation and characterization of single cells
  as well as for high-sensitivity revelation of DNA
  and proteic biomarkers hybridization through the
  use of nanotechnologies.

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Optical Imaging Lab _at_ CBM
? Imaging laboratory for fluorescence and
bioluminescence images acquisition and
analysis ? Molecular biology laboratory for
fluorescent tracer synthesis ? Cell culture
laboratory ? Animal housing and preparation
room ? Gaseous anaesthesia apparatus
Pre-clinical optical imaging system eXplore Optix
GE Healthcare. Developed by ART Advances Research
Technologies Inc.
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NMR Laboratory Metabolomics _at_ CBM
Equipment
Applications

• Characterisation of organic molecules
• Drug discovery
• Drug and receptor interactions
• Analysis of complex mixtures
• Metabonomics
• Food research
• Three-dimensional structure determination of
  molecules and small soluble proteins in solution
• Protein dynamics
• Mapping of protein-protein binding interfaces
• Semi-Solid and tissues characterization
• Heteronuclear NMR
• Characterization of inorganic chemical complexes

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LaNaDA

• 2) Optical Tweezer
• The lab is equipped with a fluorescence
  microscope with optical tweezers capability.
• The combination of fluorescence signals with
  optical tweezers allows the manipulation of
  single molecule and analysis in vitro and in
  living cells. At the same time it is possible to
  apply and measure force in the pN range. For
  instance we have measured the force exerted by
  cellular structures and living neurons.
• Our custom made Optical Tweezers use a laser
  light at 1064-nm wavelength of a 5W single-mode
  CW fiber laser (IPG Photonics YLM-10). For Force
  Spectroscopy and measure displacements in the nm
  range, the Hamamatsu S5981 position-sensing
  quadrant photodetector (QPD) is used. All
  hardware (including peripheral devices) is
  synchronized by an extremely precise real-time
  control board. This ensures the greatest accuracy
  for experiment timing and the experiments can be
  done by remote control.

• 1) Scanning Probe BioNanoAnalysis
• The facility provides for a complete imaging of
  living samples with spatial resolution at a
  nanometric level. The unique combination of
  optical and fluorescence microscope together with
  scanning force microscopy and raman spectroscopy
  allows a complete characterization of structural,
  mechanical, molecular and chemical properties of
  biological sample at a subcellular level.
• Services offered
• Advanced scanning probe microscopy (SPM)
• SPM in vivo
• SPM in combination with high resolution optical
  microscopy
• SPM in combination with fluorescence microscopy
• 3D metrology with 1nm resolution
• Measurement of mechanical properties
• force spectroscopy
• elasticity mapping
• elasticity mapping in vivo
• Micro-Raman spectroscopy
• Micro-Raman spectroscopy on individual cells in
  vivo

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LaNaDA (2)

• 3) Laser Cell Manipulation and Chemical Analysis
  (LCM-CA) Station
• The goal of this project (run in collaboration
  with CNR- Istituto Nazionale per la Fisica della
  Materia, Laboratorio Nazionale TASC, Trieste) is
  to setup a flexible microscope based station and
  run advanced cell biology experiments.
• The system accomplishes the following functions
• cell manipulation by means of IR laser
  tweezers
• cell microsurgery using pulsed UV laser
• cell chemical analysis by means of micro-Raman
  spectroscopy
• cells imaging - visible light and fluorescence
  microscopy.

• 4) NanoBioMed unit
• The NanoBioMed unit of LANADA is able to offer
  their facilities for drug development and
  characterization also for third parties and
  providing a service for particle preparation,
  quality control, and analysis of bound drug
  molecules.
• Quality control of nanoparticle preparation by
  Nanosizer NS (Malvern), size determination down
  to 0.5 micrometer, surface charge determination
  for particle up to 6 mm
• Long-term stability of colloidal preparation by
  Malvern Turboscan LabExpert
• HPLC (high pressure liquid chromatography,
  Agilent 1100 Series) analysis of complex matrices
• For cell investigation and other imaging
  problems we can offer high quality confocal
  fluorescence microscopy solutions in vivo and on
  long-terms.
• High quality fluorescence microscopy imaging with
  advanced fluorescence techniques
• Spectral analysis of emission
• Advanced fluorescence technique
• Multiphoton excitation

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BioNanoAnalysis Lab _at_ CBM

• Equipment
• Bio-AFM
• Topographical images with lt1nm lateral and
  vertical resolution
• Mechanical characterization of biological
  tissues
• microscopy in vivo (incubator at 37C)
• Optical microscopy
• Zeiss axiovert 200
• Fluorescence
• Spectroscopy
• two DPSS lasers (532nm and 473nm) with lt 30MHz
  bandwidth
• Spectrograph 750mm 3 gratings best energy
  resolution lt 1cm -1
• EM-LT CCD
• Tip enhanced Raman
• Bottom ilumantion

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NanoBioMed - Collaborations
Collaborations
This advances have opened dynamic pathways
between public research organizations and the
Optical Imaging laboratory, based on long term
co-operation programmes with a high potential for
increasing knowledge-sharing

• University of Göttingen (Germany), Department of
  Hematology and Oncology Diagnostic Radiology
• Medizinische Universität Wien (Austria),
  Department of Dermatology, Immunodermatology,
  Experimental Allergy
• University of Trieste (Italy), Department of
  Pathology and Physiology
• Institute of Child Health IRCCS Burlo Garofolo,
  Trieste (Italy), Department of Pediatric Surgery
• Mario Negri Institute, Milan (Italy)
• ADIENNE srl, Bergamo (Italy)
• Bracco Imaging S.p.A., Ivrea (italy)

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Information and contact details

• CBM s.c.r.l.
• AREA Science Park
• Strada statale, 14 - km 163,5
• Basovizza 34012 TRIESTE
• ITALY
• www.cbm.fvg.it
• info_at_cbm.fvg.it
• Tel. [phone]
• Fax [phone]

Knowing is not enough we must apply Willing is
not enough we must do Goethe