Developmental Biology Developmental Toxicology
Developmental Toxicology in the 21st Century:
Multidisciplinary Approaches using Model Organisms and Genomics
September 20-22, 2001
NIEHS
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Developmental Toxicology in the 21st Century: Multidisciplinary
Approaches using Model Organisms and Genomics
September 20-22, 2001
NIEHS
Conference Concept
Scope: The conference will bring together three areas:
Genomics/Proteomics in Developmental Biology and Toxicology,
Integration of Signaling Pathways in Development (comparative
inter-species aspects), and Models of Genetically Sensitized Organisms
(genetic susceptibility aspects). The conference is aimed at both
state-of-the-science and forward vision perspectives.
Purpose: The purpose of this conference is to bring together a
multidisciplinary group of research scientists (molecular biologists,
molecular geneticists, toxicologists, developmental biologists,
including transgenic/ mutagenesis/ genomic experts using mouse,
zebrafish, Drosophila, C. elegans and other relevant animal models, in
a joint forum to discuss the current state of emerging
multidisciplinary knowledge relevant to evolutionarily conserved and
shared developmental biology and toxicology mechanisms. The potential
for expanding our understanding of the relationship of developmental
biology and toxicology mechanisms and environmental agent exposure(s)
in originating functional and/or structural developmental defects in
animal models relevant to the human condition will be explored.
Venue: This is a 2 ½ day meeting held September 20th (Thursday) to
the 22nd (Saturday), 2001 at the NIEHS Rodbell Conference Center and
the Radisson Governor's Inn Hotel in Research Triangle Park, NC.
Sponsorship: The meeting is sponsored by the NIEHS, NIH Office of
Rare Diseases, U.S.-EPA and the American Chemistry Council.
Background: Recent advances in developmental biology, molecular
biology and genomics present a unique and timely opportunity to build
research designed to examine the site and mechanism of action of
developmental toxicants and to thereby set the stage for
environmental- based intervention and prevention strategies. The
sequencing of the human and a variety of animal genomes (yeast, fruit
fly, zebrafish and roundworm) is providing fundamental information
about genome organization, evolution (which will aid species
extrapolation) and polymorphisms that will allow for a more complete
understanding of gene-environment interactions. Major discoveries have
recently been made in the areas of components, mechanisms and
processes of normal development at the molecular level in various
models including the fruit fly, zebrafish, frog, and the mouse.
Seventeen signaling pathways are currently recognized which are used
in common during development and differentiation by these species and
it appears that the molecular components of these processes are
substantially conserved among animal phyla, c.f., "Scientific
Frontiers in Developmental Toxicology and Risk Assessment", National
Academy Press, 2000). Since the same signaling pathways exist in the
round worm, fruit fly, zebrafish, mouse, and human, these animal
models could potentially be used to examine the effects of chemical
agents on the expression and function of these fundamental pathways,
to identify chemical agents that are useful tools for both
investigating the molecular mechanisms underlying development, and for
evaluating whether a chemical's impact on these pathways in humans can
be predicted based on the responses in the model organisms. An
example of this is the use of the mutational analysis in the fruit fly
that lead to the discovery of homeobox genes with their subsequent
identification in all other species. In addition there are over 25
zebrafish strains with heart defects in which the defective gene is
known. By examining such data on heart defects it may be possible to
start the process of linking heart defects and (a) defective gene(s)
caused by endogenous or exogenous environmental agent exposure(s).
The principles of integrative developmental biology and toxicology are
undergoing a revolution - a revolution that is being marshaled by
integrative multidisciplinary research and fueled by new strategies
for applying the powerful new "omics" technologies to well
characterized animal models that may generate data translatable to the
human condition. This conference seeks to envision new research
approaches that will lead toward this emerging horizon.
Agenda:
September 20th (Day 1)
8:15- 8:30 A.M. Welcome
8:30- 8:45 Conference Overview
Session 1- Developmental Research in the 21st Century: Looking Up the
Road Ahead
8:45- 9:15 Birth Defects: Rates, Causes and Cost to Society
Louis Holmes (MGH/Boston)
9:15- 9:30 Coffee break
9:30-10:30 A Vision for Developmental Biology Research in
the 21st Century
John Gerhart ( UC-Berkley)
10:30-11:00 A Vision for Developmental Toxicology Research in
the 21st Century
Elaine Faustman (U. Washington)
11:30- 12:30 P.M. Lunch break
12:30- 1:30 Using Genomics to Understand Normal and Abnormal
Development:
From What Baseline(s) forward?
Eric Green (NHGRI, NIH)
1:30- 2:30 Using Proteomics to Understand Normal and
Abnormal
Development:
From What Baseline(s) forward?
Rudy Aebersold (Institute for Systems
Biology, WA)
2:30- 2:15 Coffee break
2:15- 2:45 Capitalizing on Large-Scale Mutagenesis
Screens: Is Mouse the Measure of Man?
Monica Justice (Baylor College of Medicine)
2:45- 3:15 Integrating Retinoids, Embryonic Development,
and the Zebrafish Genome
Elwood Linney (Duke University)
3:15- 3:45 Genomic Approaches to Understanding Methyl Mercury
Developmental Toxicity
Thomas Knudsen (Thomas Jefferson
University Medical College)
3:45- 4:15 Genomic Approaches to Understanding Phenytoin
Teratogenicity
Richard Finnell (University of Nebraska)
4:15- 6:00 Poster Session
6:00 - Free evening
September 21st (Day 2)
Session 2- Signal Transduction Pathways and Development: Modeling
Regulatory
Intersections and Outcomes
8:15- 9:00 A.M. Comparative Human/Mouse Genomic Sequence
Analysis: Insights into Functional
Interpretations and Annotations
Terry R Magnuson (UNC School of Medicine)
9:00- 9:45 Systematic Analysis of Human Disease-Associated
Gene Sequences in Drosophila melanogaster:
Morphogens and "A Unity of Opposites" in
Developmental Biology?
Ethan Bier (UC-San Diego)
9:45-10:00 Coffee break
10:00-10:30 Integration of Signaling Pathways in Development
(pending confirmation)
10:30-11:00 Cyclopamine and Shh Signaling
Henk Roelink (University of Washington)
11:00-11:30 Teratogen-induced Apoptotic Signaling
Philip Mirkes (University of Washington)
11:30-12:30 P.M. Lunch break
Session 3: Model Organisms: What they Tell Us About Development
12:30- 1:30 Models for Cell Type Activation and Repression:
Genetic Models of Signaling Pathways
Responsible for Gene Induction
William Wood (University of Colorarado)
1:30- 2:30 Using Genetically "Sensitized" Model Organisms
to Understand Normal and Abnormal Development
Mark Fishman (Harvard Medical School)
2:30- 2:45 Coffee break
2:45- 3:15 Regulatory Pathways of Morphogenesis
in a Zebrafish Model
Randy Peterson (MGH/Charlestown)
3:15- 3:45 Regulatory Pathways of Morphogenesis
in a Drosophila Model
Carl S. Thummel (University of Utah)
3:45- 4:15 Gestatational Toxicant Exposure Effects
on Organogenesis in the Mouse
Richard Peterson (University of Wisconsin)
4:15- 4:45 Using Model Organisms to Screen for Low Dose
Chemical Induced Dysmorphogenesis
Geoffrey Dyuk (Exelixis, Inc.)
6:00- 7:00 Catered Conference Dinner (Radisson Governor's
Inn)
7:00- 9:00 Concurrent Breakout Groups (Radisson Governor's
Inn)
I. Genomics/Proteomics
II. Signaling Pathways
III. Model Organisms/Genetically
Sensitized
Model Organisms
September 22nd (Day 3)
Session 3 - From Molecules and Pathways to Tissues and Organs
7:15- 8:15 A.M. Catered Breakfast (NIEHS Conference Center)
8:15- 9:15 Genomic Information Management Systems in
Embryos: A Sea Urchin Genome's View of the
Developmental and Evolutionary Regulatory
Systems for Designing Animals.
Eric H. Davidson (California Institute of
Technology)
9:15- 9:45 From Mechanisms to Histogenesis:
The Potential of Embryonic Stem Cells
Roger Pedersen (University of
California-San Francisco)
9:45-10:15 From Mechanisms to Morphogenesis:
Heart Development
Eric Olsen (University of Texas
Southwestern Medical Center)
10:15-10:30 Break
10:30-11:00 From Mechanisms to Morphogenesis:
Central Nervous System Development
Gary Schonenwolf (University of Utah)
Session 4 - Challenges and Opportunities for Applying the New
Developmental Biology and Toxicology to Public Health Risk Assessment
11:00-11:45 Developmental Biology: The Potential for
Multidisciplinary Integrative Developmental
Biology and Toxicology Research
Virginia Papaioannou (Columbia University
College of Physicians and Surgeons)
11:45-12:15 Developmental Toxicology: The Potential for
Integrative Contribution to Public Health and
Risk Assessment Research
Elaine Faustman (University of Washington)
12:15- 1:00 P.M. Conference Summary Report: Research Prospectus for
Genomics/Proteomics, Signaling Pathways and
Potentials for Genetically
Characterized/Sensitized Model Organisms
Robert Kavlock (U.S.-EPA)
1:00 P.M. Adjourn
Shuttles to RDU Airport (6 mi.) for afternoon
flights
Michael E. McClure, Ph.D.
Chief, Organs and Systems Toxicology Branch
Tele: 919-541-5327
Division of Extramural Research and Training
Fax: 919-541-5064
National Institute of Environmental Health Sciences, NIH
E-Mail: mm461n at nih.gov
111 T.W. Alexander Drive
Courier: 79 T.W. Alexander Dr
P.O. Box 12233, Mail Drop EC-23
Bldg. 4401, Rm. 3417
Research Triangle Park, North Carolina 27709
RTP. NC 27709
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