Zebrafish has been developed as a model for drug characterization. As zebrafish have similar brain chemistry to humans, especially the neurochemistry underlying their rest/wake cycles, they can be used to screen compounds affecting behavior. In addition, using zebrafish instead of mice for drug profiling greatly reduces animal costs. The Schier lab has developed an automated screening technique for monitoring sleep/rest cycles in zebrafish, allowing the study of the effects of drug candidates on behavior. The effects of novel drugs can be compared to known drugs and side effects can be deduced from behavioral profiling.

The genetic tractability of zebrafish also allows them to be used for genetic screens. Dr. Schier has developed a model of insomnia in zebrafish that is based on hypocretin (Hcrt) overexpression. Hcrt is a known mammalian sleep/wake regulator, and the Schier lab has found that the expression pattern and activity of larval zebrafish Hcrtis similar to those in mammals. As a result, Hcrt overexpression affects zebrafish waking cycles, promoting wakefulness and inhibiting rest. This zebrafish insomnia model can be used for the investigation of drugs to combat insomnia.

• Using zebrafish as a model system to investigate the genes and circuits that regulate sleeping.
• Screening sleep-altering drugs for human use.
• Genetic and pharmacological screens to isolate sleep regulators.
• Electrophysiological approaches to dissect sleep circuits.
• Developing in vivo imaging techniques for analyzing the neural circuits regulating sleep.
• Using human stem cell technology to generate hypocretin neurons from narcoleptic subjects to determine the molecular basis of neural degeneration in these patients.

• Zebrafish as a drug profiling model
• Hypocretin overexpression as insomnia model
• Automated zebrafish screening
• Behavior model
• High throughput screens
• Human stem cells
• Image analysis and in vivo imaging
• Zebrafish models
• High throughput screening
• In vivo small molecule screening

http://news.harvard.edu/gazette/story/2010/01/zebrafish-point-the-way/

The Schier lab has developed assays and large-scale screens for measuring sleep and wakefulness in zebrafish. Awake zebrafish can be distinguished from sleeping fish based on behavioral analysis, and zebrafish have similar brain chemistry to humans, making them ideal for studying human sleep disorders. They are also developing in vivo imaging techniques for analyzing the neural circuits regulating sleep. Dr. Schier is also using human stem cell technology to generate hypocretin neurons from narcoleptic subjects to determine the molecular basis of neural degeneration in these patients.

Biological Mechanisms and Pathways

• Central Nervous System (CNS) •
• Circadian clock •
• Developmental biology •
• Genetics •
• Hypocretin (Hcrt) •
• Nervous system •
• Networks •
• Neural circuits •
• Sensory neuron •
• Signal transduction •
• Sleep
•  

Central Nervous System

• Cognition •
• Hypocretin (Hcrt) •
• Neural circuits •
• Sensory neuron •
• Sleep
•  

Disease Mechanisms

• Insomnia
•  

Research Tools and Instrumentation

• Automated zebrafish screening •
• Behavior model •
• Genetic screen •
• High Throughput Screening •
• Image analysis •
• In vivo imaging •
• Insomnia model •
• Zebrafish models
•  

Therapeutic Discovery Tools and Assays

• High Throughput Screening •
• In vivo small molecule screening
•