More than 80% of the C. elegans proteome has been estimated to have human homologs, indicating a high degree of protein function conservation. The ease of genetic manipulations and availability of a detailed synapse-resolution wiring diagram allow the system to model neurological disorders and address their defects across the synapse, cell, and circuit resolution.
We have established and discovered the C. elegans models for the following disorders: ALS (Murakami, 2015), CLIFAHDD (Aoyagi, 2015), JBS (Chitturi et al. 2018), and migraine (Huang et al. 2019). In all models, locomotory behaviours are the functional readout to dissect the underlying molecular, cellular, and circuit mechanisms of the causative genetic mutations.
In fact, it was through our work on neuronal excitability that we identified the first case of CLIFAHDD, a neurodevelopmental disorder caused by gain-of-function mutations in the human homologue of the sodium leak channel. We are continuing to utilize these animals to diagnose, understand, and seek treatment of these disorders.