Drug discovery is the process through which potential new medicines are identified. Developing a new drug from original idea to the launch of a finished product is a complex process which can take 12–15 years and cost in excess of $1 billion. Researchers select drug targets by developing a hypothesis that the modulation of a protein or pathway will result in a therapeutic effect.One of the most important steps in developing a new drug is target identification. This is accomplished by data mining available biomedical data and through the use of phenotypic screening to identify disease relevant targets. Once identified, the target then needs to be fully validated. Transgenic animals as well as small interfering RNA (siRNA) are attractive validation tools as they involve whole animals and allow observation of phenotypic endpoints to elucidate the functional consequence of gene manipulation.
C. elegans is a useful model for both target identification and early validation. By taking advantage of modern genetics, including the ability to create humanized worms, researchers can quick vet hypotheses to discover new drug targets and interactions.
Introducing the ScreenChip System: a platform for drug screening & discovery
The effects of ivermectin, an antiparasitic agent, can be observed in an irregular pumping pattern and shape in the video.
The ScreenChip phenotyping platform enables real-time, quantitative phenotypic measurements of live, un-anaesthetized worms without the need of high-speed cameras and post-hoc measurements. You can:
- Easily load worms into recording channel and measure drug effects on large populations of individuals
- Directly measure the phenotypic readout and behavioral response from drug compounds and changes to chemical composition
- Directly observe therapeutics in a whole animal with high throughput and low expense
Key advantages of the ScreenChip system phenotyping assays:
- Measure the phenotypic readout of genetic and pharmacological manipulations on humanized worms (Fig. 1)
- Accelerate drug discovery by quickly and easily screening putative drugs on known clinical variants of genes (Fig. 2)
- Rapidly gather and analyze preliminary data to optimize experiments (Fig. 3)
- Understand mechanisms contributing to side-effects of known drugs and compounds (Fig. 4 & 5)
Measure the phenotypic readout of genetic and pharmacological manipulations on models of human disease.
Fig. 1: Visualize disease phenotypes to test drug efficacy. Neimann-Pick Type C (NPC), a lysosomal storage disorder characterized by a cholesterol trafficking deficit, can be effectively modeled in worms. This worm (left) is an NPC model with lipid content visualized using the RediStain™ WormDye Lipid Green kit.
Accelerate drug discovery by quickly and easily screening putative drugs on known clinical variants of genes
Fig. 2: Phenotype of Niemann Pick Type C model worms. This phenotype can be used as a basis for drug discovery. Genetic mutations resulted in a reduction in pumping rate in ncr-1 mutants (left graph) and long interpump duration (right graph) in the absence of cholesterol.
Rapidly gather and analyze preliminary data to optimize experiments
Fig. 3: The effects of fluoxetine (ProzacTM) on C. elegans health. Wild-type worms exposed to low concentrations of fluoxetine show increase in mean pumping frequency. (n = 24 and 32 for 0.0 and 0.1mg/ml).
Understand mechanisms contributing to side-effects of known drugs and compounds
Fig. 4: The ScreenChip System reveals effects of cannabinoids. In C. elegans, anandamide produces hyperphagia, a potential correlate of marijuana munchies. One of the legendary effects of cannabinoid drugs is increased motivation to eat or hyperphagia.
Fig. 5: Worms exposed to anandamide have higher feeding rates than controls. (top) Representative data from individuals in each treatment show an increase in pumping rate. (bottom) The cannabinoid Anandamide induces hyperphagia in adult worms (red dots).