Biological model

At Nagi Bioscience we automate and standardize working with one of the most studied model organisms in science: the microscopic nematode Caenorhabditis elegans.

Sydney Brenner

Caenorhabditis elegans: a powerful model organism, nature’s gift to science

Caenorhabditis elegans has been known for over 60 years as an important exploratory organism in fundamental research. It helps in addressing various biological questions in the fields of aging, neurobiology, genomics, and developmental and cellular biology. Despite its relative simplicity, this nematode possesses multiple well defined tissues and displays an extensive variety of behaviors, ranging from locomotion or feeding to some complex social behaviors. To this date, large amounts of mutant, transgenic and “humanized” worm strains are widely available. C. elegans is also distinguished by the ease of genetic manipulations: single genes can be simply inactivated by feeding the worms with bacteria expressing dsRNA against the gene of interest (RNA interference method). Nowadays, any specific strain can be generated easily “on-demand” using modern CRISPR-Cas9 techniques.

We enable ”in vivo testing at the in vitro scale”!

Significantly less expensive and devoid of ethical constraints associated with research in vertebrates, C. elegans assays still provide data from a whole animal with intact and metabolically active digestive, reproductive, endocrine, sensory and neuromuscular systems. This allows   the investigation of complete in vivo responses at whole-organism level. At the same time, the microscopic size and relative simplicity of C. elegans, combined with Nagi’s unique “Organism-on-Chip" technology, permits its manipulation with in vitro handling techniques and renders the work amenable to high-throughput and high-content screening formats, which previously were only accessible with cell cultures. Our C. elegans-based bioassays hence nicely bridge the gap between in vitro and mammalian in vivo testing. Our technology enable studying complex phenomena implicating organ cross-talk or age-dependent changes that are impossible to explore in cellular models, but with the cost- and time- ratios of in vitro assays.

C. elegans in numbers
In vitro - In vivo

A scientifically validated solution in drug discovery and toxicology

C. elegans has been emerging as a valuable alternative to rodent and cellular models in pharmaceutical research[1] and toxicology[2],[3],[4],[5],[6]. It can be successfully used for phenotype-based drug screenings, as well as for identifying drug targets and mechanisms of action. Being a key model in aging research, C. elegans can be used in screens to identify pro-longevity compounds. In the same manner, worm strains that model neurodegenerative diseases or muscular dystrophies can help in the discovery of potential therapeutics for  these disorders[7],[8].

For toxicology, multiple toxicity pathways and modes of action are conserved between worms and humans. Toxicity data obtained in C. elegans proved themselves to be predictive of outcomes in mammals[9] and the LC50 ranking in C. elegans matches the LD50 ranking in mouse and rat.

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References

  1. Leung et al. Caenorhabditis elegans: An Emerging Model in Biomedical and Environmental Toxicology. Toxicol Sci. 2008
  2. Hunt. The C. elegans model in toxicity testing. J Appl Toxicol, 2016
  3. Harlow et al. The nematode Caenorhabditis elegans as a tool to predict chemical activity on mammalian development and identify mechanisms influencing toxicological outcome. Sci Rep, 2016
  4. Racz et al. Application of Caenorhabditis elegans and Danio rerio embryo as model systems to screen for developmental and reproductive toxicity of Piperazine compounds. Toxicol In Vitro, 2017
  5. Lahm et al. The discovery of fluazaindolizine: A new product for the control of plant parasitic nematodes. Bioorg Med Chem Lett, 2017
  6. Shamalnasab et al. A salicylic acid derivative extends the lifespan of Caenorhabditis elegans by activating autophagy and the mitochondrial unfolded protein response. Aging Cell, 2018
  7. Sleigh et al. A novel Caenorhabditis elegans allele, smn-1(cb131), mimicking a mild form of spinal muscular atrophy, provides a convenient drug screening platform highlighting new and pre-approved compounds. Hum Mol Genet, 2011
  8. McCormcik et al. Dopamine D2 receptor antagonism suppresses tau aggregation and neurotoxicity. Biol Psychiatry, 2013
  9. Boyd et al. Developmental effects of the ToxCast Phase I and II chemicals in Caenorhabditis elegans and corresponding responses in zebrafish, rats and rabbits. Environ Health Perspect, 2016