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High Throughput Screening for Biological Systems
16 March - 17 March 2009
High Throughput Screening for Biological Systems
The aim of this conference is to enable detailed investigation of high throughput systems for those dedicated to using primary or stem cell sources as biologically relevant models. Whether the aim is drug target discovery, toxicology testing, or histological analysis, this event will explore advances in technology and new strategies to acheive maximum results.
With the right approach, advances in automation and cell culture techniques can be utilized to access and vizualise biological events.  This is a “purpose-built” event to convey information that is specific and valuable to those engaged in automated cell screening.  Emphasis on imaging, including new ways to identify cellular activity, data analysis and applications will provide researchers the tools they need to progress. 
The majority of techniques currently employed to interrogate a biomolecular interaction require some type of radio, enzymatic or fluorescent labelling to report the binding event. However, there is an increasing awareness of novel techniques that do not require labelling of the ligand or the receptor, and that allow virtually any complex to be screened with minimal assay development. Our expert line-up of speakers will provide proof-of-concept studies for these novel technologies.

                                                                     

  • Andy Tee, Head of Reagent Provision for the HTS group, Pfizer

          

Conference agenda

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8:30

Registration & Coffee

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9:00

Chairman's Opening Remarks

Simon MacKenzie

Simon MacKenzie, Head of Laboratories, Scottish Biomedical

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9:10

ADVANCES IN PROTEIN AND ANTIBODY STRUCTURAL MODELLING

  • Use of a rich rotamer library and a Unary Quadratic Optimisation algorithm to address protein sidechain predictions in homology modelling

  • Specific techniques for homology modelling of antibody structures; knowledge-based domain-specific libraries and canonical methods; loop grafting to produce chimeric templates

  • Validation examples

  • Susan Boyd

    Susan Boyd, , Chemical Computing Group

    Steve Maginn

    Steve Maginn, Director, Scientific Services, Chemical Computing Group

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    10:00

    ADDRESSING PROTEIN-PROTEIN INTERACTIONS FOR GPCR, KINASE & NHR DRUG TARGETS USING A COMPLEMENTATION-BASED TECHNOLOGY SUITABLE FOR CELL-BASED HIGH THROUGHPUT SCREENING

    Keith Olson

    Keith Olson, Vice President R&D, DiscoveRx

  • The use of enzyme-based complementation
    assays versus conventional methods
  • Protein-protein interactions, directly addressing
    cellular events at the target protein of interest
  • GPCR targets, directly measuring receptor activity
  • NHR targets, a focus on nuclear translocation
    and binding to co-regulator proteins
  • Receptor tyrosine kinases, using the protein
    interaction between the active RTK and SH2-
    domain containing proteins
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    10:50

    Morning Coffee

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    11:20

    TARGET VALIDATION TO SMALL MOLECULE BLOCKER IDENTIFICATION: NOVEL APPROACHES TO PROTEIN-PROTEIN INTERACTION DRUG DISCOVERY

    Simon MacKenzie

    Simon MacKenzie, Head of Laboratories, Scottish Biomedical

  • Assessment of protein-protein interaction
    target validation approaches
  • Assay development first steps, is the target
    interaction druggable?
  • Defining successful assay strategies
  • Comparing cell free and cell based approaches
  • Hit confirmation and deconvolution
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    12:10

    DISCUSSIONS, QUESTIONS AND PROBLEMS FROM THE AUDITORIUM

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    12:30

    Close of Workshop

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    8:30

    Registration & Coffee

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    9:00

    Chairman's Opening Remarks

    Andy Tee

    Andy Tee, Head of Reagent Provision for the HTS group, Pfizer, Pfizer Global R&D

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    9:10

    USE OF LABEL-FREE CELL BASED ASSAYS IN DRUG DISCOVERY

    Frank Stuhmeier

    Frank Stuhmeier, Senior Principal Scientist, Discovery Biology, Pfizer

  • Improving the physiological correctness of assays. 
  • Evaluating several plate based label free assay technologies
  • Outline the advantages and disadvantages of the different label free systems
  •  Potential benefits of label free technologies, as well their integration into the drug discovery process.
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    9:50

    APPLICATIONS FOR PRIMARY CELLS IN HTS

    Oliver Nayler

    Oliver Nayler, Director, Actelion

  • Primary vs. recombinant cells as biological model systems
  • Are pathway predictions possible?
  • Comparison of assay formats
  • Examples from GPCR drug discovery programmes
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    10:30

    Morning Coffee

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    11:00

    DEALING WITH THE BOTTLENECKS IN HIGH THROUGHPUT CELL SCREENING

    Andy Tee

    Andy Tee, Head of Reagent Provision for the HTS group, Pfizer, Pfizer Global R&D

  •  Manual and robotic (SelecT) provision of cells for HTS
  •  Logistics involved
  •  Possible use of ‘paused’ cells
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    11:40

    OPTICAL LABEL-FREE IDENTIFICATION OF GPCR

    Isabel Coma

    Isabel Coma, Investigator, GlaxoSmithKline

  • Plate-based label-free biosensors as a versatile platform
  • Detection of cell mass redistribution upon activation of a particular GPCR
  • Simplifying hit identification strategies
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    12:20

    Networking Lunch

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    13:30

    STREAMLINED ANALYSIS OF LARGE MULTIPLEXED CELLULAR ASSAYS

    Stephan Heyse

    Stephan Heyse, Head, Screener Business Unit, GeneData

  • Data analysis from a process perspective
  • Intelligent integration of kinetics and label-free assays
  • Systematic processing of high-content screens
  • Optimizing qualification and quantification of biological activity
  • Managing complexity, increasing hit quality
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    14:10

    A HUMAN TOPONOME PROJECT DECIPHERING THE PROTEIN NETWORK CODE (TOPONOME) OF HUMAN DISEASES FOR IMMEDIATE PHARMACOLOGICAL AND CLINICAL APPLICATIONS

    Walter Schubert

    Walter Schubert, Head, Molecular Pattern Recognition Research Group, University Of Magdeburg

  •  Illustrating all the steps from toponome data generation to data analysis and functional annotation of interlocked protein clusters, including the detection of lead proteins, which exert control over protein network topology and function in tumor cells
  • Evidence will be provided showing  that toponome analysis using the TIS technology (i) leads to detection of disease specific protein networks, (ii) new key target proteins (lead proteins) and treatment strategies,  (iii) new biomarkers, and (iv) sensitive Tox assays with protein networks as read out
  • TIS is the first ultra-high content / high throughput technology with very short detection times of up to few weeks or months, and apparently with very low error rates
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    14:50

    A CELL BANKING PROCESS FOR THE PROVISION OF CRYO-PRESERVED, “ASSAY-READY” CELLS FOR DRUG DISCOVERY PROGRAMMES

    Jim Cooper

    Jim Cooper, Senior Project Manager, European Collection Of Cell Cultures (ECACC)

  •  Cell culture process optimisation – use of metabolite analysis and live cell imaging techniques
  •  Establishment of a process that produces pilot material to the exact specification and methodology of the production material
  • Quality control - criteria and release
  •  Functional performance
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    15:20

    Afternoon Tea

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    15:40

    A MULTIPLEXED APPROACH TO HIT FINDING

    Thomas Hesterkamp

    Thomas Hesterkamp, SVP Discovery Biology, Evotec

  • Synergistic applications of HTS, Fragment based screening, virtual screening and high content screening
  • Selection of the best possible readout
  • Sensitivity screening for low-affinity interactions
  • Orthogonal / counter screening readouts
  • Mechanism of action studies (activators / inhibitors)
  • Eliminating falses e.g. false –ves and false +ve
  • Multiple / allosteric binding site interactions
  • Case studies
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    16:20

    FROM IMAGING AND DETECTION TECHNOLOGIES FOR ION CHANNELS DRUG DISCOVERY

    Sabrina Corazza

    Sabrina Corazza, Enabling Technologies Group, Axxam

  • generation of cell based assays for ion channels
  • application of luminescent and fluorescent technologies for functional studies of ion channels
  • screening examples
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    17:00

    IMAGING –BASED ASSAYS FOR NEUROSCIENCE

    Kalpana Patel

    Kalpana Patel, Investigator, GlaxoSmithKline

  • Learn about plate-based cellular assay to measure dendrite spine number in neuronal cultures, with automated imaging and analysis   capability
  • Development of an assay to measure growth cone area with automated image analysis capability.
  • 2 relevant assays for neuroscience drug discovery, in addition to the well described neurite outgrowth assay
  • Assays deployed for target identification and validation
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    17:40

    Chairman’s Closing Remarks and Close of Day One

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    8:30

    Registration & Coffee

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    9:00

    Chairman's Opening Remarks

    Martin Stoter

    Martin Stoter, Scientist, High Content Screening, Max Planck Institute of Molecular Cell Biology and Genetics

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    9:10

    ALLOSTERIC MODULATORS OF TRKB:BDNF ACTIVATION: DISCOVERY OF ACTIVE, NON-PEPTIDIC, SMALL MOLECULES AGAINST A PREVIOUSLY INTRACTABLE TARGET

    Stephen Ashman

    Stephen Ashman, Investigator, Biological Reagents and Assay Development, GlaxoSmithKline

  • Introduction and target validation
  • Screening strategy
  • Novel HTS format and summary of HTS output
  • Hit characterisation/pharmacology
  • Novel HTS format and summary of HTS outputs
  • Secondary pathway assays
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    9:50

    SOFT SPOT ID: IN VITRO SCREENING FOR METABOLIC STABILITY TO PROVIDE CHEMISTRY ALTERNATIVES

    Alfred Zimmerlin

    Alfred Zimmerlin, Head of Metabolism, Novartis Pharma

  • More than 25% of research compounds are metabolically unstable in vitro and many fail   for this reason in-vivo
  • Pathway elucidation (soft spot identification) is performed too late to really impact chemistry
  • In Silico softspot prediction is not good enough to be used first line
  • When in silico predictions can be supported by experimental evidence rationale chemistry efforts can be initiated
  • New technologies and improvements in analytical science will allow compound optimisation for ADME at the very same time as for pharmacological activity
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    10:30

    Morning Coffee

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    11:00

    TRANSIL BRAIN ABSORPTION: A NOVEL IN VITRO TEST FOR PREDICTING CNS PENETRATION

    Hinnerk Boriss

    Hinnerk Boriss, CEO, Sovicell

  • The TRANSIL Brain Absorption assay kit is used to predict plasma/brain equilibrium distribution (logBB) and the compounds’ free fraction in brain as well as the compounds' ability to CNS+ and CNS- compounds.
  • The prediction error for the plasma to brain distribution is less than 0.22 logBB units.
  • The predicted free fraction in brain correlates highly with in vivo free fractions (r2=0.94).
  • Reliable classification of compounds entering the brain is based on availability in brain and the speed at which compounds pass the blood brain barrier.
  • The assay not only predicts CNS penetration not only for compounds targeting the brain but also side effects of compounds in other indication areas.

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    11:40

    HIGH-CONTENT CELL-BASED ASSAYS AND RNAi TECHNOLOGY USED TO STUDY FUNCTIONAL GENOMICS

    Martin Stoter

    Martin Stoter, Scientist, High Content Screening, Max Planck Institute of Molecular Cell Biology and Genetics

  •  Multi-parametric image analysis
  • Over 60 parameters extracted
  • 3-colour system
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    12:20

    Networking Lunch

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    13:20

    FROM THE GRAMMAR OF DRUG DISCOVERY TO PROBING THE SYNTAX OF BIOLOGICAL PATHWAYS:

    Christian Parker

    Christian Parker, Research Investigator, Novartis Pharma

  •  Phenotypic assays ,successfully in use for discovery of many most successful drugs in use.
  • The advent of reductionism biochemical approaches strategies using phenotypic responses,' fallen out of favour'.
  • Screening approaches:Reduced applications of phenotypic screens for drug discovery.
  • The development of phenotypic, cell based, assays suitable for HTS
  • Novel methods available for screening natural products and target deconvolution
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    14:00

    ALLOSTERIC MODULATORS AT G-PROTEIN COUPLED RECEPTORS: A MEANS OF INCREASING THE TRACTABILITY OF INTRACTABLE GPCR

    Stephen Brough

    Stephen Brough, Principal Scientist, GlaxoSmithKline

  • Ligand-receptor interactions – GPCRs as “allosteric proteins”
  • The return of functional screening and its role in improving tractability
  • Practical considerations in modulator screening:Case study with family C GPCR mGluR5
  • Advantages of modulators for poorly tractable targets
  • Successes, challenges and opportunities afforded by modulator ligands
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    14:40

    MEASURING ELECTRICAL IMPEDANCE AS A MEANS OF LABEL-FREE, NON-INVASIVE DETECTION

    Anker Jon Hansen

    Anker Jon Hansen, Principal Scientist, Novo Nordisk

  • Cell electrical impedance, theory and practice
  • Impedance can measure several vital cell parameters, like adhesion and proliferation
  • Screening for cellular antigens and mediators of NK-cell mediated killing
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    15:20

    Afternoon Tea

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    15:40

    PREDICTING FOR TARGETS AND ANTI-TARGETS WITH IN SILICO MEDICINAL CHEMISTRY

    Nathan Brown

    Nathan Brown, Group Leader, In Silico Medicinal Chemist, Institute of Cancer Research

  • High-throughput QSARs
  • Global and local models
  • Maximising the impact of all our data
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    16:20

    COMPUTATIONAL TOXICOLOGY AND IT'S APPLICATIONS IN LIBRARY DESIGN AND LEAD OPTIMISATION.

    Cédric Merlot

    Cédric Merlot, Head Knowledge Management & Computational Chemistry, GenKyoTex

  • Learn what are the benefits of following-up predictions with in vitro and in vivo testing.
  • Conversely, why it is important to complement in vivo experiments and in vitro assays with in silico predictions.
  • From theory to practical applications
  • Case study: Learn how the combination of predictions and in vivo follow up has prevented big issues that would have risen during clinical development
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    17:00

    Chairman’s Closing Remarks and Close of Conference

    Copthorne Tara Hotel

    Scarsdale Place
    Kensington
    London W8 5SR
    United Kingdom

    Copthorne Tara Hotel

    The Copthorne Tara Hotel London Kensington is an elegant contemporary four-star hotel in prestigious Kensington, located just a two minutes walk from High Street Kensington underground station, making exploring easy. The hotel offers well-appointed and comfortable guest rooms combining Standard, Superior and Club accommodation. Club rooms offer iconic views over the city and include Club Lounge access for complimentary breakfast and refreshments. Guests can sample the authentic Singaporean, Malaysian and Chinese cuisine at Bugis Street, traditional pub fare at the Brasserie Restaurant & Bar or relax with a delicious drink at West8 Cocktail Lounge & Bar.

    The Copthorne Tara Hotel boasts 745 square meters of flexible meeting space, consisting of the Shannon Suite and the Liffey Suite, ideal for hosting conferences, weddings and social events. Facilities include access to the business centre 24 hours a day, fully equipped fitness room, gift shop, theatre desk and Bureau de Change. With ample onsite parking outside the London congestion charge zone and excellent transport links via Heathrow Airport, the hotel is the perfect location for business or leisure stays. The hotel is within close proximity to the shops of High Street Kensington, Knightsbridge and Westfield London, Olympia Conference Centre, Royal Albert Hall, Kensington Palace and Hyde Park.

     

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    WHAT IS CPD?

    CPD stands for Continuing Professional Development’. It is essentially a philosophy, which maintains that in order to be effective, learning should be organised and structured. The most common definition is:

    ‘A commitment to structured skills and knowledge enhancement for Personal or Professional competence’

    CPD is a common requirement of individual membership with professional bodies and Institutes. Increasingly, employers also expect their staff to undertake regular CPD activities.

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    CPD AND PROFESSIONAL INSTITUTES

    There are approximately 470 institutes in the UK across all industry sectors, with a collective membership of circa 4 million professionals, and they all expect their members to undertake CPD.

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    CPD Schemes often run over the period of a year and the institutes generally provide online tools for their members to record and reflect on their CPD activities.

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    As a formal provider of CPD certified activities, SAE Media Group can provide an indication of the learning benefit gained and the typical completion. However, it is ultimately the responsibility of the delegate to evaluate their learning, and record it correctly in line with their professional body’s or employers requirements.

    GLOBAL CPD

    Increasingly, international and emerging markets are ‘professionalising’ their workforces and looking to the UK to benchmark educational standards. The undertaking of CPD is now increasingly expected of any individual employed within today’s global marketplace.

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