Anti-cancer Drug Screening Service

The nematode Caenorhabditis elegans is a valuable tool for biological and basic medical research due to its easy manipulation at the laboratory level, its genetic tractability and well-defined developmental lineage. Besides, thanks to its great homology with human genes, the worm is an exceptional model for genetic and molecular analysis of human disease-related genes. At present, C. elegans has been widely exploited for the identification and functional analysis of drugs in vivo, including the anti-cancer agent. Here we provide a high-throughput phenotype-based screening platform for the identification of anti-cancer drugs. Notably, signaling pathways (including oncogenic signaling pathways, such as Notch, Wnt, and Ras) and their regulators in C. elegans are highly conserved in most vertebrates, including humans.

Caenorhabditis elegans as a model for anti-cancer drug discovery

The nematode C. elegans is a multicellular organism that exists as either hermaphrodites or males. The germline of the nematode is in a simple linear fashion that progresses from germline stem cells to maturing gametes. During C. elegans germline development, there are conserved external signaling pathways (including Notch, Wnt, and Ras) regulating multiple cellular processes, involving germline stem cell maintenance and niche specification, germ cell fate specification. Since aberrant control of these signaling pathways can lead to either over proliferation of a specific cell type or loss of germline stem cells, resulting in sterility. Therefore, the sterility phenotype of C. elegans facilitates an available strategy for screening anti-cancer agents that modulate the oncogenic signaling pathways directly or indirectly.

An adult wild-type (N2) hermaphrodite and its dissected germline stained with DAPI.An adult wild-type (N2) hermaphrodite and its dissected germline stained with DAPI. (Kobet, R. A., et al. 2014)

Service offerings

The C. elegans mutants

Here we provide C. elegans Notch mutants, Wnt mutants and Ras mutants for the identification of drugs that may target the conserved oncogenic signaling pathways positively or negatively.

The oncogenic signaling pathways and related mutant phenotypes
Signaling pathway Mutants Phenotypes
Wnt/β-catenin signaling ceh-22(q632) DTC loss (~40%) and partially sterile (DTC functions as a germline stem cell niche)
pop-1(q645) DTC loss (100%) and sterile (DTC functions as a germline stem cell niche)
GLP-1/Notch signaling glp-1(ar202)ts Fertile at 20°C
glp-1(bn18)ts Fertile at 20°C
Ras-ERK MAPK signaling mpk-1(ga117) Pachytene arrest and sterile
puf-8(q725) Mog sterile at 20°C
lip-1(zh15) Germline tumors at 25°C

The high-throughput drug screening

We provide an automated high-content drug screening system based on the COPASTM Worm Sorter incorporated with the red-head marker (mCherry), which enables efficient sorting of C. elegans mutants into plates. Besides, the Spot Detector is applied to automatically measure either fertility or sterility via scoring the number of viable progeny in each well.

Creative Biogene is dedicated to providing high-quality service to accelerate and improve our clients' research outcomes. We provide a phenotype-based high-throughput screening system combing advanced automated instruments for identifying anti-cancer drugs that may target oncogenic signaling pathways. If you are interested in our service, please feel free to contact us for more details.

Reference

  1. Kobet, R. A., et al. (2014). "Caenorhabditis elegans: A Model System for Anti-Cancer Drug Discovery and Therapeutic Target Identification." Biomolecules & therapeutics, 22(5), 371–383.

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