for Not-for-Profit Discount Organisations 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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We are C5 … because on every business day, executives and professionals from 5 Continents are meeting somewhere in the world at a C5 Conference. 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
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
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
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
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
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
mRNA as well as structural RNA. We designedexperiments to show the operation of this in vivo cis and
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
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 aApplication 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
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
technological advances (latent alleles, tissue-specific or
temporally regulated mutations, compound mutants) will
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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ARTICULO COMPLETO TRADUCIDO AL IDIOMA ESPAÑOL SETIEMBRE DE 2006 DISPERSION NOSOCOMIAL DE ENTEROCOCUS FAECIUM RESISTENTE A LA VANCOMICINA (ERV) Y AL LINEZOLID EN UN CENTRO MEDICO DE ALTA COMPLEJIDAD Thomas E. Dobbs, Mukesh Patel, Ken B. Waites, Stephen A. Moser, Alan M. Stamm, and Craig J. Hoesley Journal Of Clinical Microbiology, Set. 2006, p. 3368-3370. R
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