C. elegans in high-throughput drug discovery

Abstract

C. elegans has proven to be a useful model organism for investigating molecular and cellular aspects of numerous human diseases. More recently, investigators have explored the use of this organism as a tool for drug discovery. Although earlier drug screens were labor-intensive and low in throughput, recent advances in high-throughput liquid workflows, imaging platforms and data analysis software have made C. elegans a viable option for automated high-throughput drug screens. This review will outline the evolution of C. elegans-based drug screening, discuss the inherent challenges of using C. elegans, and highlight recent technological advances that have paved the way for future drug screens.

The tales of two organic cation transporters, OCT-1 and OCT-2, in C. elegans

“…elegans as a model to facilitate studies on drug uptake transporters C. elegans has been chosen as the whole model system as it offers a multitude of advantages over mammalian cells to rapidly study many highly conserved biological processes [27]. C. elegans developed from eggs to the adult stage within three days spanning four larval stages.…”

“…C. elegans are transparent and facilitate easy visualization of germ and somatic cells by microscopy. During the last decade, C. elegans have been instrumental in several drug discovery programs that include the search for new antifungals and compounds to limit oxidative stress [27,28], although the contributions of uptake transporters in these studies were not considered [29]. Therefore, it is unclear how C. elegans uptake transporters would have influenced many of the high-throughput screens performed so far to identify novel small molecules that act, for example, as antimicrobials.…”

“…Therefore, it is unclear how C. elegans uptake transporters would have influenced many of the high-throughput screens performed so far to identify novel small molecules that act, for example, as antimicrobials. One possibility is that the yield of bioactive compounds typically recovered from these screens, ranging from 0.03 to 1 %, could be substantially higher if there is greater influx of the molecules into the animal cells via elevated expression of uptake transporters [27,30]. Thus, defining the function and substrate specificities of uptake transporters in C. elegans will be advantageous towards improving the strategies employed to identify novel bioactive molecules.…”

A microfluidic device for automated, high-speed microinjection of Caenorhabditis elegans

“…[14][15][16] These properties make C. elegans as an emerging tool for whole-animal drug testing and screening, and its complete genomic resources simplify the further drug target identification. [17][18][19] In worm-based drug testing experiments, C. elegans is exposed to drug solutions via perfusion, feeding, or microinjection, among which microinjection is the only method capable of delivering controlled amounts of drugs to specific intra-body sites. Microinjection is particularly useful for testing water-insoluble drugs for which the perfusion or feeding method is not feasible; it a) P. Song and X. Dong contributed equally to this work.…”

Automated Wormscan

“…Early efforts developed a “wormsorter”, I believe in the 1970s, which has now been commercialized as the COPAS 1  and is fairly standard in many C. elegans labs. A quick google search returned loads of other efforts at automation a few examples: drug discovery 2 , gene expression 3 , and locomotion 4 . There are also an entire host of micro-fluidics devices that are continually being published and some reference to this is also probably warranted.…”