1024C Poster - 16. Techniques and technology
Saturday April 09, 1:30 PM - 3:30 PM

Authors:
Robert Courville; Mahtab Jafari

Affiliation: University of California, Irvine, Irvine, CA

Keywords:
h. high-throughput phenotyping; u. drug discovery

Background: Drosophila melanogaster may serve as an excellent pre-clinical model system in drug discovery. Developing high throughput platform using Drosophila as a model system in drug discovery presents an efficient and cost-effective in vivo pre-clinical platform to screen and evaluate therapeutics, at the phenotypic and transcriptomic levels.
Methods: We developed two high throughput screening platforms to evaluate drug induced phenomic changes by two pharmaceuticals with distinct pharmacological properties in an outbred Drosophila population: caffeine (a stimulant) and haloperidol (a sedative). The evaluated phenotypes were fecundity and behavioral changes; locomotion, feeding patterns, and sleep. To evaluate fecundity, flies were divided into mating pairs and transferred into vials with removable caps containing the drug/yeast solution. After 24 hours of mating, digital images of vial caps were created using a scanner in groups of 40 by treatment, and the images were uploaded into ImageJ where a custom macro autonomously counted the eggs. To evaluate behavioral changes, we optimized the Activity Recording Cafe (ARC), a machine-vision system that allows for automated behavioral measurements. Flies were sexed into groups of 30 and habituated in ARC chambers for 24 hours. Machine vision settings were calibrated for optimal frame tracking and data were collected for 24 hours autonomously. Behaviors were measured at days 14 and 20 from eclosion. Transcriptomic analysis will be done at the UC Irvine Genomics High-Throughput facility using heads, ovaries, and testes.
Results: Both drugs impacted fecundity in an age specific manner. Caffeine increased fecundity in days 19-28 (p<0.05) but had no impact on fecundity on days 14-18. Haloperidol decreased fecundity in days 14-18 (p<0.05) and had no impact on fecundity in other ages. Caffeine increased fly activity and feeding relative to controls (p<0.05), and decreased sleep (p<0.05). Haloperidol showed decreased activity at both ages (p<0.05), but no significant differences in feeding or sleep. All phenomic assays are currently being replicated. Transcriptomic analysis is in progress. The efficiency (time and cost) of these high-throughput assays will be compared with conventional assays and the data will be presented on the poster.
Conclusion: The phenomic data show that the high throughput screening platforms were sensitive enough to detect drug induced phenomic changes.