www.vtt.

fi/mbt

VTT Technical Research Centre of Finland

VTT Technical Research Centre of Finland

Medical Biotechnology

Lila Kallio, Ph.D. Specialist, New Business Development

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VTT Technical Research Centre of Finland

VTT IS a globally networked multitechnological applied research organisation a not-for-profit and impartial research centre VTT HAS extensive cross-disciplinary technological and business expertise unique research infrastructure comprehensive global partnership networks in business, industrial and research communities VTT CREATES new technology and science-based innovations in co-operation with domestic and foreign partners

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VTTs status as performer of R&D work

Basic research

Applied research

VTT

Development

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VTT on map

Berkeley and Washington, USA

Saint Petersburg, Brussels, Russia Belgium Seoul, South Korea Shanghai, China Tokyo, Japan

Finland
Sodankyl

Turku

Kuopio Jyvskyl Tampere Rajamki Helsinki Espoo

Rovaniemi

Oulu Raahe Kajaani

So Paulo, Brazil

Outokumpu

Lappeenranta

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VTT Group in brief

Turnover 307 M (2011) Personnel 3,187 (31.12.2011)

Customer sectors
- Biotechnology, pharmaceutical and food industries - Electronics - Energy - ICT - Real estate and construction - Machines and vehicles - Services and logistics - Forest industry - Process industry and environment

Focus areas of research

- Applied materials - Bio- and chemical processes - Energy - Information and communication technologies - Industrial systems management - Microtechnologies and electronics - Services and the built environment - Business research

VTTs operations
- Research and Development - Strategic Research - Business Solutions - Business Development - Group Services

VTTs companies
- VTT Expert Services Ltd (incl. Labtium Ltd, Enas Ltd) - VTT Ventures Ltd - VTT International Ltd (incl. VTT Brasil LTDA) - VTT Memsfab Ltd

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VTTs research projects

1 Commercial activities
Commercial activities performed according to direct demand from customers. Impact: Building competitiveness for VTTs customers through world-class research and innovation services

2 Joint projects

3 Self-financed research
Technology-based strategic research projects

Research projects jointly funded by VTT, companies, research financers (*) and/or other research parties. Impact: More efficient technology transfer Foundation for new innovations and political decision-making

Impact: Developing VTTs own competitiveness and acquiring knowledge and expertise to meet future customer needs

(*)

R&D funding possibilities for example Tekes (The Finnish Funding Agency for Technology and Innovation) EU projects

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VTT Medical Biotechnology (MBT)

The VTT-MBT in Turku was established in 2002 Critical mass of talented scientist/staff members (>60), state-of-the-art instrumentation and modern infrastructure Over 40 peer-reviewed publications annually Research projects with top Pharma companies, SMEs, and universities We provide cost-efficient preclinical research services using versatile cell, molecular biology and protein biochemistry techniques Drug target discovery and validation Hit discovery and hit-to-lead confirmation Drug effect and MoA studies Ready-to-use and customized high-throughput and high-content screening platforms
Cell biology OMICS/HTS Immunotech Engineering Informatics Translation

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In vitro Cell Biology for H&W

In Vitro Cell Biology
Technology development (next-gen biochips, 3-D models) Drug target discovery and validation at genetic and protein levels Identification of new therapeutics + drug repurposing Cell division and signalling research + metabolomics Instrumentation HT-robotics core Versatile imaging facility Modern laboratories Biacore T-200 Reagent Libraries 70K LMW compounds +140 human cell lines Genome-wide RNAi Genome-wide miRNA (antimiR and pre-miR)

Focus on cell-based assays Functional drug assays (MoA, EC50) Toxicity and safety (chemical / material) In vitro cell-based metabolomics Target identification and validation Bio-informatics In-depth knowledge of cell signalling pathways Immunotechnologies for cell research

Research Services

Enabling Technologies HT-robotics platforms In vitro biochips Protein arrays 3-D organotypic models Immunotechnologies Imaging platforms In-silico tools and software

Bio-Informatics Data analyses (from genes to proteins and pathways) Development of solutions and software Data visualisation and navigation

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Applications of VTTs in vitro cell biology technologies

Cancer cell, mitosis and cell adhesion signaling RNAi and gene overexpression phenotyping High-throughput and high-content screening Proteomic profiling with lysate microarray

Organotypic 3D cell models State-of-the-art live cell microscopy Recombinant antibody development Metabolomics platforms

We also develop novel technologies together with our customers.

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What can we offer you

Drug target discovery and validation, hit discovery and hit-to-lead confirmation, drug mechanism-of-action studies using VTTs proprietary technologies Individual technologies or technology combinations depending on customers specific needs Cost-effectiveness through streamlined work processes Scientific data interpretation Combination of in-depth knowledge on cell signaling and cancer biology with modern research methodologies Detailed information on the compounds cellular mechanism-of-action in cells Hit identification with ready-to-use or customized high-throughput screening platforms Generation and development of recombinant antibodies based on customers needs combined to various technology platforms Bioinformatics services to complement the result analysis

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Added value for the customer

Flexibility: tailor-made projects Project content and schedules depending on customers needs Individual VTT technologies can easily be combined to larger entities Combination of scientific know-how and world class technologies VTT proprietary technologies such as the Cell Spot Microarray and 3D cell culture models Professional ISO 9001:2008 certified project management and trustworthiness through rigorous quality control We will perform a full bio-informatics analysis and scientific interpretation of the obtained results as agreed with the customer, instead of providing raw screening data Our valued customers include e.g. Bayer HealthCare, Roche, and Santen

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High-throughput and high-content screening

Chemical compound libraries Genome-wide siRNA and miRNA libraries o Focused sets of epigenetics, cell cycle, and cancer gene targeting sub-libraries o Custom siRNA libraries can be designed based on the customers needs Functional screens with selected technologies and endpoint HTS for cancer cell growth suppressive novel LMW molecules HTS for drug repositioning (from other indications towards anti-cancer purposes) Toxicity assays A variety of different assays can be optimized to HTS on customers demand Compound and RNAi HTS in 3D cultures and in primary cells

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Cell Spot Microarrays (CSMA)

Discovery and validation of drug targets with highly miniaturized platform for cell-based RNAi screening Genome-wide ultra HT RNAi screening (28.000 siRNA species in a single microtiter plate) Rapid testing of subgenomic RNAi sets according to customers interests (e.g. kinases and phosphatases, GPCRs, druggable genome, epigenetic regulators) High-content screening for multiparametric phenotypes designed according to the customers needs Can replace conventional 384-well plate-based screens Proprietary technology developed by VTT

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Principle of CSMA
1. siRNA molecules as spotted as microarrays 2. Cells are added on top 3. Cells adhere on spots and take up siRNA 4. In each spot one gene of the genome is silenced individually 5. Multiparametric assays for gene silencing effects

Ultra-high-throughput assays

150m

Samples from 120 x 384-well plates with robotically made siRNA transfection mixtures 46.000 transfections with spots150m in diameter and 375m spacing in single plate

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Applications of CSMA

A functional genomics tool for drug discovery and development with applications in Drug target discovery and validation in high-content with multiple parameters Compound screening (miniaturization enables screening also when the amount of compound or other reagents is limited) Testing of the gene/drug sensitization effect in ultra HT manner Modulation of drug efficacy by siRNA-mediated synthetic lethal gene-knockdowns Mechanism-of-action studies
CSMA is validated with over 90 different cell lines (Rantala et al. BMC Genomics 2011, 12:162)

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Benefits of using Cell Spot Microarray

Multiparametric phenotype analysis Long term cell culture possible
More information

All samples with up to 28.000 siRNAs are analyzed in a single chip -> No interassay variability
Reliable and reproducible

Miniaturization enables HTS also when cells or other material (e.g. compounds) are limited
Rapid and costeffective

Fully compatible with microarray scanners -> Readout for genomescale screen with four markers in <20 min
Very fast results

20x less cells required -> Compatible with rare cell types e.g. primary or patient-derived cells
Less cells needed

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The Protein Lysate Microarray

Proteomic profiling of a large number of biological samples with specific antibodies Biomarkers, diagnosis, clinical prognosis, prediction of therapeutic responses (personalized medicine)
RNAi

Drug

Clinical samples

Cultured cells Printing of lysates into arrays on slides

Multiple copies of the array slide enable multiple different analyses from same sample

Endpoint analysis for protein profiles

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3D Models for complex biology

Enabling platform: miniaturized 3D organotypic cell model Recapitulates the key aspects of solid cancers Multicellular tissues Complex cell-cell interactions 3D cell model is an important validation step between conventional cell studies and animal testing VTT's 3D cell model enables characterization of dynamic phenotypic features in a complex tissue microenvironment Integrated solution that covers the whole package from cell culture to image analysis

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Applications of 3D organotypic cell model

non-invasive spheroids

invasive spheroids

High content screening for drug target discovery and drug effect validation, MoA studies: Compound screening with various endpoints
proliferation apoptosis and cell death differentiation growth dynamics invasion

Time courses and dose-response relationships Drug sensitization and synthetic lethality screens Toxicity assays

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Benefits of using VTT's 3D organotypic cell culture platform

Improved efficiency: VTT's 3D platform facilitates experiments in low (miniaturized) volume in multiplex Miniaturization reduces material (e.g. reagents, 3D matrix) costs per experiment Multiplexing through miniaturization saves time as many assays can be done in parallel All-in-one assays (several endpoints) Tumor cell invasion can be credibly studied AMIDA software for dynamic imaging Statistics Quality control

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Competitive advantage
VTT's 3D model enables studies in more natural tumor microenvironment Co-cultures of different cell types Based on biologically relevant semisolid matrices (e.g. laminin-rich ECM Matrigel) Supports complex morphological differentiation processes such as acinar morphogenesis and invasion Automated image analysis by AMIDA VTT's proprietary integrated software package Morphological classification Quantitation of dynamic effects VTT's 3D culturing system enables real-time live cell monitoring for up to 4 weeks Essential when testing cells having complex biological processes Ideal for studying dynamic morphological processes and responses, such as invasive transformation 3D cell culture can also be performed in high-throughput 384-format for certain endpoints (e.g. proliferation)

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Multiplex diagnostics with Arrays-in-wells (AIW)

A microarray platform and a reader device for multiplex diagnostics of samples in small quantity Applications Rapid viral diagnostics Analyte panels for e.g. cardiovascular diseases Pathogen diagnostics Autoimmune disease Allergy Genotyping Diagnostics for animal diseases, food borne pathogens and environment

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VTT - 70 years of

technology for business and society