C. elegans Drug Screening Service

The nematode Caenorhabditis elegans has proven to be a valuable model organism and widely used for the studies of gene function and the complex molecular processes. More recently, the nematode has been exploited as a powerful tool for drug discovery due to its genetic and molecular tractability, amenability to high-throughput screening methods, experimental cost-effectiveness, and fast turnaround among others. Despite the numerous experimental advantages of C. elegans, the drug screens are labor-intensive and time-consuming. Recent advances in high-throughput workflows, imaging platforms and data analysis software promote the worms as a viable option for automated high-throughput drug screens. Herein, we provide the advanced instruments and optimal protocol to help customers conduct drug screening, including anti-infective compounds, drugs against neurodegenerative diseases, pro-longevity compounds, and anti-cancer drugs. In addition, we also offer customized pipelines to identify drug targets and mechanisms for the particular needs of our customers.

Drug discovery using C. elegans

C. elegans is a microscopic soil nematode that plays a pivotal role in elucidating genetic pathways associated with important cellular processes such as cell death, development, ageing among others. Thanks to its great homology with human genes, the worm is also an exceptional model for genetic and molecular analysis of human disease-related genes. Consequently, C. elegans has been extensively exploited to model complex human diseases and related-disease drug discovery, such as Alzheimer's disease, Parkinson's disease, diabetes and cancers. There are several major advantages of using C. elegans in high-throughput screening (HTS).

  • The characteristics of C. elegans, including small size, short lifespan, the ability of both living in solid and liquid culture conditions among others.
  • As a whole organism, the nematode enables to model complex human diseases in vitro that can't be easily reproduced in unicellular models.
  • C. elegans can be used in the initial stages of the drug discovery pipeline and enables the evaluation of drug efficacy, metabolism and toxicity characteristics at the same time.
  • C. elegans has multiple scorable phenotypes.
  • The availability of advanced genetic tools and genomic resources facilitates drug target identification.

Evolution of C. elegans-based drug discovery

Despite C. elegans having been used for drug screening since 1973, it is reported that the first use of C. elegans on agar plates for large-scale drug screens was in 2006. Automated transfer instruments and semi-automated image acquisition were applied for compounds testing via evaluating a variety of phenotypes, including slow growth, uncoordinated movement, and lethality. Thanks to the development of the all-liquid workflow, automated robotic liquid handlers and the integration of automated imaging platforms in C. elegans-based drug discovery were accessible. In 2010, the first automated high-content drug screen integrating automated worm transfer, image acquisition and data analysis was reported. The picture below shows us the historical timeline of C. elegans-based drug discovery.

The historical timeline of C. elegans-based drug discovery. The historical timeline of C. elegans-based drug discovery. (O'Reilly, L. P., et al, 2014)

Service offerings

  • Anti-infective compounds screening service

C. elegans has been incorporated into small molecule screening, especially for novel anti-infective compounds. The nematode lives in a natural environment where it is exposed to bacterial and fungal pathogens. For anti-infective compounds screening, C. elegans not only offers the ability to identify molecules that promote innate immune responses for host survival and compounds that interfere with bacterial virulence mechanisms, but also provides an in-assay counter-screen against toxic molecules. Here, we offer anti-infective agent screening services, involving immunostimulatory compounds, anti-virulence compounds, and pathogen-targeting compounds.

  • Drug screening against neurodegenerative diseases service

Given that there are highly conserved neurological pathways between C. elegans and mammals, the simple nematode is extensively used for neuroprotective compound screening. We have developed the NDs-related phenotype by expressing the human gene in C. elegans for the drug screening against neurodegenerative diseases (NDs). On our platform, the most common NDs drug screening service is based on a high-throughput automated drug screening system, involving Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and Amyotrophic lateral sclerosis (ALS).

  • Pro-longevity compounds screening service

We also provide an automated platform for the identification of potential pro-longevity compounds. We exploit the differential C. elegans phenotypic and biochemical changes associated with mild mitochondrial stress, as surrogate markers to establish a phenotypic-based screening. This is a new C. elegans screening strategy that can drastically accelerate the discovery of potential life-extending compounds.

  • Anti-cancer drug screening service

Oncogenic signaling pathways and their regulators in C. elegans are highly conserved in humans, such as Notch, Wnt, and Ras signaling pathways. We provide the related signaling pathway mutants for the identification of anti-cancer drugs. In addition, the automated high-content drug screening system based on the COPASTM Worm Sorter and Spot Detector are employed to accelerate and improve the drug screening process.

Creative Biogene is a dedicated provider of C. elegans model services. We are dedicated to accelerating the speed to achieve customers' research goals with high-quality, and also provide the customized service to suit the particular needs of customers' research. If you are interested in our service, please feel free to contact us for more information.

References

  1. Strange K. (2016). "Drug Discovery in Fish, Flies, and Worms". ILAR J.57(2):133-143.
  2. O'Reilly, L. P., et al. (2014). "C. elegans in high-throughput drug discovery. Advanced drug delivery reviews." 69-70, 247–253.

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