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for Not-for-Profit
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Harnessing the potential of model organisms as a discovery
research tool: expediting target identification and validation
16th and 17th September 2004
Hear latest developments in:
Kempinski Hotel Bristol, Berlin
RNAi in vivo
Gain unique insight from our exceptional speaker panel:
Conditional/
Inducible systems
Jan Tornell
Antony Purchio
ASTRAZENECA R&D
Systemic phenotyping
Gerard Dawson
Thomas Rosahl
Lentiviral transgenesis
MERCK, SHARP & DOHME
MERCK, SHARP & DOHME
In vivo imaging
Dave Lewis
Paul Schofield
Zebrafish in drug discovery
MIRUS CORPORATION
UNIVERSITY OF CAMBRIDGE
Bjorn Rozell
Luk Van Parijs
KAROLINSKA INSTITUTE
MASSACHUSETTS INSTITUTE
CONFERENCE CHAIRMEN
Laurence Fiette
OF TECHNOLOGY
INSTITUT PASTEUR
Jan Tornell
AstraZeneca R&D
Sponsored by
Johannes Beckers
Institute of Experimental
Genetics, GSF - National
Research Centre for
Environment and Health, GmbH
SCIENTIFIC ADVISOR
Supporting Association
Mohamed Slaoui
Aventis Pharma
INTERNATIONAL MAMMALIAN GENOME SOCIETY
To register call +44 (0) 20 7878 6888.or fax +44 (0) 20 7878 6885.
or visit our website at www.C5-Online.com/invivo
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In Vivo and Transgenic Models
Aventis Pharma, Merck, Sharp & Dohme,
AstraZeneca, MIT, Institute Pasteur, Cambridge
University, and many other key industry players.
improved optimisation andmore effective target The conference will provide first-hand experience and feedback on how companies and academia are harnessing the potential of in vivo models: production of customised, humanised, conditional Lentiviral-based transgenesis and RNAi in vivo models is rising to meet the needs of researchers inboth academia and industry. Conditional and inducible transgenic systems This C5 conference brings together the latest
technologies and examples of models being utilised and developed for screening and functionalanalyses. This highly focused and intensive conference will be examining how specific and Zebrafish and customised, humanised rodent complex in vivo modelling and transgenesis is being achieved with respect to knock-in/out, ENUmutagenesis, RNAi and lentiviruses in zebrafish and In two information-packed days, gain invaluable insight rodents. Experts in the field will discuss how they into the top issues for all functional geneticists, have developed these models and the future pathologists and those involved in target validation and drug discovery seeking to develop the next generationof medicines. Attend this conference and hear from animpressive group of experts working in the field of Register today to reserve your place at this in vivo and transgenics, including speakers from: SPONSORSHIP AND EXHIBITION OPPORTUNITIES AT THIS EVENT
This event will provide an excellent opportunity for companies to promote their services and products to senior level decision makers. Get information about promotional packages which best suit your company's objectives, including networking and pre-arranged, face-to-face meeting opportunities, branding and sponsorship. For more information contact: Pete Mitchell on +44 (0) 20 7878 6875 or email [email protected]
To register call +44 (0) 20 7878 6888.or fax +44 (0) 20 7878 6885.
or visit our website at www.C5-Online.com/invivo
Role of conventional gene knock-out and transgenic Thursday 16 September 2004
Drug binding site alterations in vivo (knock-in mice) Registration and Coffee !
Target validation for anxiety and anaesthesiafranchise using knock-in mice Chairman's Opening Address
Recombineering for efficient transgenesis Jan Tornell, M.D., Ph.D.
Director, AstraZeneca R&D
Proof of Concept for a Novel Technological
TARGET VALIDATION
Approach for Producing Genetic Rat and
Mouse Models on an Industrial Scale
The Role of Transgenics in the
Discovery of New Medicines —
Klaus Dembowsky, M.D., Ph.D.
Past, Present and Future
Vice President of Drug Discovery
Ingenium Pharmaceuticals
Jan Tornell, M.D., Ph.D.
Knock-out models in mice are time consuming and estimates indicate that as many as one third of animals do not display AstraZeneca R&D
a phenotype. There is a clear need for alternate animalmodel technologies, both to produce genetic rat models and Areas where transgenic technology has been to provide alternative methods to rapidly produce genetic mouse models. Industrial use of ENU mutagenesis can meet both these needs. Examples will be given how this technology can improve and accelerate target validation.
Understanding mechanisms underlying toxicity Proof-of-concept results for using ENU to generate genetic rat models on an industrial scale techniques enhance translation of finding Limitations of ES-cell technology in the mouse: Do mouse models provide predictive power for Use of ENU to produce genetic models based on point defining a good target for drug development? mutations as opposed to complete gene knock-outs Importance of genetic models based on point Customised, Conditional
mutations as opposed to complete gene knock-outs Genetically Modified Mouse
Applications in drug target validation, drug discovery Generation for Drug Discovery
and disease research for ENU-generated geneticmouse models, including knockouts and beyond Paul Rounding, Ph.D.
Luncheon
Managing Director, Business and Operations
Artemis Pharmaceuticals GmbH
Use of Genetically Modified Rodent Models
ArteMiceTM allows the generation of adult conditional for Target Validation and Lead Optimisation:
KO mice, ready for use in experiments, within seven New Approaches to Overcoming
months. Our expertise in construction of large vectors, Limitations of Current Technologies
and our ES cell expertise allows us to generatecomplex humanised mouse models for drug discovery.
We have generated adult RNAi knock down Kader Thiam, Ph.D.
ArteMiceTM in three months that show 80% knock down of gene expression in all tissues. We will Head of Business Development, GenOway
describe how these techniques can be used to Genetically modified animal models have been intensively used in biomedical research. Nevertheless the outcome of these experiments could be uncertain based on model design. GenOway has developed a Tools and reagents for and utility of conditional wide range of strategies allowing the development of evolving models fulfilling specific needs.
Humanising of mouse genes, rapid generation of sophisticated custom models for drug discovery In vivo RNAi, reliable conventional and conditional Morning Refreshments
and gene knock-down (safe knock-out and safe RNAi transgenesis) Beyond Conventional Gene
Knock-outs and Transgenics
Thomas Rosahl, Ph.D.
in vivo pharmacological models (humanisation) Merck, Sharp & Dohme
In vivo follow up of effector's mechanism Gene knock-out and transgenic mice have been employedextensively to identify and validate potential drug targets.
Production and Characterisation of
However, gene targeting can also be used to introducespecific alterations into drug binding sites on receptors, Mouse Mutants for Inherited Diseases
which allows a sophisticated analysis of the drugmechanism in an animal model. Moreover, conditional Johannes Beckers, Ph.D.
transgenic technologies may simulate acute changes in disease state resembling aspects of drug intervention.
GSF - National Research Centre for Environment
and Health, Institute of Experimental Genetics
Friday 17 September 2004
Most functional properties of biological molecules are stillunpredictable from in silico sequence analysis. Systematic Re-registration and Coffee !
gene invalidation and gene activation experiments have tobe performed using various mutagenesis strategies in Chairman's Opening Address
particular in mammalian model organisms. Suchmutagenesis strategies have been established for the Johannes Beckers, Ph.D.
mouse and are currently used at the GSF in large-scale, Head of Expression Profiling & Gene Regulation Group genome-wide mutagenesis and gene-specific projects.
Institute of Experimental Genetics
GSF - National Research Centre for
Environment and Health, GmbH
Goals of the International Mouse Mutant Consortium Large-scale chemical mutagenesis using the mouseas model for disease RNAI IN VIVO
Standardised and comprehensive phenotyping ARCHAEAEXPRESS: Regulated
of mouse models: The German Mouse Clinic.
Expression of Specific mRNAs in the
Afternoon Tea and Networking !
Mouse Induced by the Expression of
an Archaeal Endonuclease
Panel Discussion
Glauco Tocchini-Valentini
This interactive Q&A session will enable delegates to raise any specific questions directly to our expert ISTITUTO DI BIOLOGIA CELLULARE, CNR
panellists, and other members of the audience. Areas for discussion include: We generated a new system for manipulating geneexpression at the post-transcriptional level by Are knock-outs and transgenic mice the most expressing an archaeal endonuclease that excises small valuable for target validation or for providing tRNA introns (Deidda et al.; Nature Biotech., 21:1499- 1504, 2003). Archaea encode an RNA ligase that joins the resulting exonic fragments created by this action, The pitfalls of technology: Do they live and it turns out that mouse cells have an endogenous ligase with equivalent activity. The only requirement ofthe archaeal endonuclease is a bulge-helix-bulge Panellists:
recognition motif in its target RNAs, that is, a structure Jan Tornell, M.D., Ph.D.
rather than a specific sequence; this allows great freedom in creating and presenting diverse targets in AstraZeneca R&D
mRNA as well as structural RNA. We designedexperiments to show the operation of this in vivo cis and Johannes Beckers
trans splicing scheme in mouse cells and in mice.
Head of Expression Profiling & Gene Regulation Group Induced trans-splicing results in the production of fusion- anel Discussion Institute of Experimental Genetics, GSF - National
proteins. This emergent technology can be used to P Research Centre for Environment and Health, GmbH
Dr. Gerard R. Dawson
Performing RNAi in Adult Mammals
Senior Director & Head of In Vivo Neuroscience
Merck Sharp & Dohme Research Laboratories
Dave Lewis, Ph.D.
Senior Scientist - RNA Interference
The Role of Zebrafish in Drug Discovery
Mirus Corporation
Paul Goldsmith, M.D., Ph.D.
In order to use RNAi in adult mammals, methods forefficiently delivering siRNAs or siRNA expression constructs are required. This presentation will focus on Daniolabs Ltd
the development of non-viral delivery technologies in By combining relevant, high quality disease models in large and small model mammalian species. Applications zebrafish with gradable, scalable assays, Daniolabs including target validation and evaluation of chemically has conducted compound screens across several therapeutic areas and identified both lead compoundsand novel targets. This talk will build on this work to illustrate how and where most value can be obtained from zebrafish in vivo disease modelling.
Impact of siRNA modifications on activity and longevity in mice How they may be utilised in drug discovery Morning Refreshments
Chairman's Closing Remarks
Close of Day One
7878 6888. or fax +44 (0) 20 7878 6885. or visit our website a Application of Stabilised
In Vivo Biophotonic Imaging:
siRNA in Mouse Models
Applications for Oncology
and Gene Expression
André Lochter
Director Business Development
Antony Purchio, Ph.D.
Atugen AG, Berlin, Germany
Vice President and Chief Scientific Officer RNAi using siRNA-mediated gene silencing is a Xenogen Corporation
powerful tool for gene function analysis. The short Gene knock-out and transgenic mice have been bio-availability of conventional siRNA molecules is, employed extensively to identify and validate however, an impediment for functional in vivo potential drug targets. However, gene targeting can applications. Non-modified siRNA molecules are rapidly also be used to introduce specific alterations into degraded by nucleases in serum and other body fluids.
drug binding sites on receptors, which allows a Atugen has processed towards in vivo applications of sophisticated analysis of the drug mechanism in an siRNA molecules by the development of novel stabilised animal model. Moreover, conditional transgenic siRNA structures, which differ significantly from the technologies may simulate acute changes in disease conventional siRNA molecules in terms of nucleotide state resembling aspects of drug intervention.
composition, length of the molecules and covalentmodifications. This advancement opens the potential Tracking and monitoring primary tumours and metastases in vivo Afternoon Tea and Networking !
Where do Transgenic Mice make a
DISEASE MODELLING
Difference in CNS Drug Discovery
Computing on Pathology: Approaches
Dr. Gerard R. Dawson
to the Coding of Complex Phenotype
Senior Director & Head of In Vivo Neuroscience Data and Database Resources for the
Merck Sharp & Dohme Research Laboratories
Discovery of Gene Function
Target identification and drug optimisation with transgenic animals Paul Schofield, Ph.D.
Senior Lecturer in Anatomy, Department of Anatomy University of Cambridge
Relative success of transgenic mice in developingnew therapeutic approaches to neurological diseases A key aspect of mutant mouse phenotyping is systematic Challenges of developing transgenic models pathological analysis. In order to enable computers to use pathology data as part of the investigation of genefunction we have developed an ontology for mousepathology, MPATH, which may be used as part of a Desirable Alterations of the Genome
larger description framework for overall phenotype. in Mice for Drug Discovery by the
Exchangeable Gene Trap Method
Description frameworks for mouse phenotype;specifically pathology MPATH; structuring and curating the ontology Ken-Ichi Yamamura
Trans Genic Inc.
Pathbase: The need for a database for laboratorymouse pathology images Chairman's Closing Remarks
Structure and use of Pathbase reference: Resources on Pathbase Close of Conference
Modelling Cancer in Mice
Laurence Fiette DVM, DESAPV, Ph.D.
Veterinary Diagnosis Plateform
UNIVERSITY OF GENEVA
Modelling cancer has been a great challenge for a long Presidents/VP
Drug Discovery
time. First engineered murine models have provided of Research and
scientists
insights into the key pathways of tumourigenesis, butalso shown unexpected results and limits. Recent Development
technological advances (latent alleles, tissue-specific or Chief Scientific
temporally regulated mutations, compound mutants) will Geneticists
Officers
better mimic the in vivo cancer history.
Pharmacogeneticists
Pathologists
Lessons in cancer learnt through mouse models Senior Scientists
Gene Expression
Scientists
Heads/VPs of R&D
Luncheon
C5, 2004
(Please photocopy for additional delegates)
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Source: http://www.transgenic.co.jp/en/pressrelease/pdf/20040916.pdf