High-throughput Screening and Biosensing with Fluorescent <em>C. elegans</em> Strains

The nematode Caenorhabditis elegans is a powerful model organism that has been widely used to study molecular biology, cell development, neurobiology, and aging. Despite their use for the past several decades, the conventional techniques for growth, imaging, and behavioral analysis of C. elegans can be cumbersome, and acquiring large data sets in a high-throughput manner can be challenging. Developments in microfluidic “lab-on-a-chip” technologies have improved studies of C. elegans by increasing experimental control and throughput. Microfluidic features such as on-chip control layers, immobilization channels, and chamber arrays have been incorporated to develop increasingly complex platforms that make experimental techniques more powerful. Genetic and chemical screens are performed on C. elegans to determine gene function and phenotypic outcomes of perturbations, to test the effect that chemicals have on health and behavior, and to find drug candidates. In this review, we will discuss microfluidic technologies that have been used to increase the throughput of genetic and chemical screens in C. elegans. We will discuss screens for neurobiology, aging, development, behavior, and many other biological processes. We will also discuss robotic technologies that assist in microfluidic screens, as well as alternate platforms that perform functions similar to microfluidics.

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Phenotypic Screening in C. elegans as a Tool for the Discovery of New Geroprotective Drugs

Pharmaceuticals ◽

10.3390/ph13080164 ◽

2020 ◽

Vol 13 (8) ◽

pp. 164 ◽

Cited By ~ 1

Author(s):

Sven Bulterijs ◽

Bart P. Braeckman

Keyword(s):

High Throughput ◽

High Throughput Screening ◽

Aging Process ◽

Population Aging ◽

Model Organisms ◽

Pharmacological Interventions ◽

C Elegans ◽

System A ◽

Age Related ◽

Screening Strategies

Population aging is one of the largest challenges of the 21st century. As more people live to advanced ages, the prevalence of age-related diseases and disabilities will increase placing an ever larger burden on our healthcare system. A potential solution to this conundrum is to develop treatments that prevent, delay or reduce the severity of age-related diseases by decreasing the rate of the aging process. This ambition has been accomplished in model organisms through dietary, genetic and pharmacological interventions. The pharmacological approaches hold the greatest opportunity for successful translation to the clinic. The discovery of such pharmacological interventions in aging requires high-throughput screening strategies. However, the majority of screens performed for geroprotective drugs in C. elegans so far are rather low throughput. Therefore, the development of high-throughput screening strategies is of utmost importance.

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Discovery of small molecule inhibitors for the C. elegans caspase CED-3 by high-throughput screening

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2017.07.100 ◽

2017 ◽

Vol 491 (3) ◽

pp. 773-779 ◽

Cited By ~ 1

Author(s):

Scott J. Brantley ◽

Steven W. Cotten ◽

David R. Lamson ◽

Ginger R. Smith ◽

Rihe Liu ◽

...

Keyword(s):

Small Molecule ◽

High Throughput ◽

High Throughput Screening ◽

Small Molecule Inhibitors ◽

C Elegans

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High-throughput small molecule screen identifies inhibitors of microsporidia invasion and proliferation in C. elegans.

10.1101/2021.09.06.459184 ◽

2021 ◽

Author(s):

Brandon M. Murareanu ◽

Jessica Knox ◽

Peter Roy ◽

Aaron W. Reinke

Keyword(s):

High Throughput ◽

High Throughput Screening ◽

Treatment Options ◽

Screening Method ◽

C Elegans ◽

Automated Method ◽

Intracellular Parasites ◽

Chemical Inhibitors ◽

Animal Phyla ◽

Small Molecule Screen

Microsporidia are a diverse group of fungal-related obligate intracellular parasites that infect most animal phyla. Despite the emerging threat that microsporidia have become to humans and agricultural animals, few reliable treatment options exist. To identify novel chemical inhibitors of microsporidia infection, we developed a high-throughput screening method using Caenorhabditis elegans and the microsporidia species Nematocida parisii. We screened the Spectrum Collection of 2,560 FDA-approved compounds and natural products to identify compounds that prevent C. elegans progeny inhibition caused by N. parisii infection. We developed a semi-automated method for quantifying C. elegans progeny number in liquid culture, confirming 11 candidate microsporidia inhibitors. We show that five compounds prevent microsporidia infection by inhibiting spore firing, and demonstrate that one compound, dexrazoxane, slows infection progression. Together, our results demonstrate the effectiveness of C. elegans as a model host for drug discovery against intracellular pathogens and provide a scalable high-throughput system for the identification and characterization of additional microsporidia inhibitors.

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