High-throughput Drosophila sleep and circadian drug screening platform

Overview

This offering is a high-throughput preclinical screening platform that uses Drosophila melanogaster to evaluate candidate compounds for sleep-modifying, circadian, and metabolic effects across the lifespan. Developed and refined over more than 15 years, the platform can process up to 1,000 flies per week, enabling evaluation of approximately 100 compounds per screening cycle. By combining automated behavioral monitoring with downstream assays for feeding, arousal threshold, metabolism, and longevity, the platform distinguishes true sleep-promoting effects from nonspecific changes in feeding or activity—a common limitation of conventional compound screens. The approach supports translational research in Alzheimer's disease, diabetes, insomnia, and other disorders involving sleep and circadian dysfunction, and is well suited for prioritizing candidates for vertebrate studies.

Technical specifications

Core capabilities:

• Automated Drosophila Activity Monitors quantifying sleep duration, sleep architecture, and circadian rhythms under both light-dark and constant darkness conditions
• High-throughput capacity of up to 1,000 flies per week, supporting screens of approximately 100 compounds
• Feeding assays to identify and exclude compounds producing nonspecific behavioral effects
• Arousal threshold measurements to assess sleep depth
• Metabolic rate profiling
• Lifelong sleep monitoring to evaluate age-dependent changes in sleep quality and compound effects on lifespan
• Capability to test combination therapies and extend to disease models including Alzheimer's, diabetes, and insomnia

Workflow:

• Step 1: Adult flies are reared on standard food and transferred to compound-containing media immediately before behavioral testing to eliminate developmental confounds
• Step 2: Compounds producing behavioral phenotypes are evaluated for feeding effects to distinguish direct sleep effects from nonspecific changes in food intake
• Step 3: Compounds passing secondary screening are evaluated for lifespan, longitudinal sleep changes across aging, and memory to define long-term effects on longevity and health-associated behaviors

Technology readiness level

The platform is fully operational and has been continuously optimized over more than 15 years. It is currently being applied to identify therapeutics that improve outcomes in humanized Alzheimer's disease models, demonstrating translational utility. The screening strategy is fully flexible and readily scalable based on the number of compounds requested, making it suitable for both focused validation studies and broader discovery campaigns. Outputs are prioritized candidates suitable for advancement into vertebrate preclinical studies.