Birds, Flies and Sea Urchin

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Birds, Flies and Sea Urchin
Moderator Pamela Lein
Rapporteur Holger Knaut
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Birds, Flies and Sea Urchin
1. Summary of Talks
2. Summary of Discussion
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Birds, Flies and Sea Urchin
1. Summary of Talks
2. Summary of Discussion
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Birds, Flies and Sea Urchin
Use of Developing Chick Embryo to
Assess Neurotoxins and Teratogens
Susan Smith
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Birds, Flies and Sea Urchin
Why use chicken in DNT screening?
1. Low cost
- eggs are cheap
- low maintenance
- automation (vaccine production)
- genetic lines available
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Birds, Flies and Sea Urchin
Why use chicken in DNT screening?
2. Neurodevelopment well-characterized
- Detailed Knowledge of Anatomy
- Plethora of Tools
- closest non-mammalian model to humans
- toxicology screening already done
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Birds, Flies and Sea Urchin
Why use chicken in DNT screening?
3. Behavior
- Amenable to Behavioral Studies
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Birds, Flies and Sea Urchin
Drosophila Models of Simple and Complex
Diseases, and their Uses in Therapeutic Screening
Alice Schmidt
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Birds, Flies and Sea Urchin
Why use fly in DNT screening?
1. In-Depth Knowledge of Neurodevelopment
2. Plethora of Tools (Possibility to mimic Human
Diseases by Mis-Expressing Human Disease
Genes)
3. Embryos amenable to High-Throughput Screening
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Birds, Flies and Sea Urchin
Why not use fly in DNT screening?
1. Flies do not absolutely mimic human disease
2. Validation of hits in flies will take a long
time
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Birds, Flies and Sea Urchin
Sea Urchin Embryos and Larvae as Biosensors for
the Study of Teratogens by Pre-Nervous
Neurotransmitter and Retinoic Acid Receptor
Ligands
Jean Lauder
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Birds, Flies and Sea Urchin
Why use sea urchin in DNT screening?
1. Pre-Nervous Neurotransmitter system
crosstalk with Growth Factors
2. Amenable to High-Throughput Screening
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Birds, Flies and Sea Urchin
1. Summary of Talks
2. Summary of Discussion
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Discussing Birds, Flies and Sea Urchin
1. Scientific Validity of the Model
1. Extrapolation of Dosage among Models and
Humans is Difficult
2. Is a Negative a real Negative/Is a Positive a
real Positive?
3. Caveats of Models
Chicken - Neurodevelopment partly different
(no Corpus Callosum) -
Analysis of Behavior not Amenable to High
Throughput
Fly - Evolutionary Distance
- Time Consuming Validation
Sea Urchin - limited to Pre-Nervous System
(Early Development) - limited to Studies of
Neurotransmitter/Growth Factors
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Discussing Birds, Flies and Sea Urchin
2. Integration of Models into DNT Screening
Lower Priority
No
Screening in Alternative Models
Screening Battery (no one Alternative Model will
do it)
Yes
Further Mechanistic Testing
Design Smarter Mammalian Tests
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Discussing Birds, Flies and Sea Urchin
3. The Future (What next?)
1. More Communication among Three Players
(Industry, Regulatory Agencies, Academics)
2. Identify Reference List of Known Positives and
Negatives
3. Identify Endpoints of DNT, Assess which Models
Address these Endpoints Best, Test Reference
List of Positives and Negatives
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Discussing Birds, Flies and Sea Urchin
4. Additional Points
1. Risk Communication (Credibility of in vitro
Testing, Convey to Public)
2. Conundrum/Liability No Animal Use vs. Best
Testing