We use the soil-dwelling, nematode worm Caenorhabditis elegans (Wikipedia entry), to investigate the molecular mechanisms of neuronal function and dysfunction. With its extremely well described nervous system of just 302 neurons, the worm offers a unique platform for such studies. One particular advantage of C. elegans that often goes unappreciated is the ability to obtain viable mutants with severely impaired neuronal function, or with extensive neuronal loss. Furthermore, these mutants can be studied genetically, thus increasing - sometimes decisively - the suitability of this organism towards dissecting neuronal development and function. For example, we can eliminate most of the motorneurons of this animal by directing expression of a toxic protein specifically in these cells. Worms will become paralyzed, but they can still grow and breed:
The consequence: From elegantly moving worms...
...to paralyzed but alive and fertile animals
Similar severe manipulations usually result in early embryonic lethality in other organisms.
Motorneuron-specific degenerin/epithelial sodium ion channels (DEG/ENaCs), such as DEL-1 and UNC-8, are involved in maintaining a smooth, alternating, sinusoidal pattern of locomotion.
DEG/ENaC ion channels expressed in neurons show punctate distribution across axonal segments.
Despite its minimalistic nervous system, C. elegans exhibits a rich repertoire of sensory capacities and behaviors. Such wide spectrum of easily discernible phenotypes can be exploited using the sophisticated genetics and molecular biology tools developed for the worm, to elucidate the molecular mechanisms underlying the wonderful faculties of the nervous system. We build on these exceptional features for our studies, focusing on the molecular mechanisms of necrotic cell death in neurodegeneration and senescent decline, the molecular mechanisms of sensory transduction and integration by the nervous system, the interplay between cellular metabolism and ageing, and the development of novel genetic tools for C. elegans research.
