Caenorhabditis elegans neuropeptide signaling and reception
Animals respond to environmental cues through alteration of neural circuits that modify behaviour and metabolism. The mechanism underlying the regulation of the neural circuit in response to a simple sensory cue is extremely complex and difficult to disentangle in mammals. The nematode C. elegans offers an excellent model organism to analyze neural circuit function. C. elegans is 1.3 mm in length and has several desirable features. These include a short generation time with each self-fertilizing hermaphrodite producing about 300 progeny. Large scale production of several million animals is possible in a day. C. elegans is multicellular. The hermaphrodite has 959 somatic cells that form different organs and tissue including muscle, hypodermis, intestine, reproductive organs and glands and nervous system.
The nervous system comprises 302 neurons whose identity and connections have been defined by morphology and ablation studies. C. elegans is also transparent such that in vivo fluorescent dyes can be used to visualize gene expression and fat metabolism in the living animal. The advantage over other systems is that alterations within a functional neuron can be studied in the context of the whole organism and rather than measuring changes in fluorescence, the actual behavioral response of the animal can be monitored directly.
C. elegans has recently emerged as an excellent paradigm for identifying the cellular mechanisms underlying human disease. Disease models are possible if the disease can be explained in molecular terms. This non-mammalian genetic model has a strong record of uncovering disease-related genes that have orthologs in the human genome. These include the uncovering of genes involved in Alzheimer’s disease, Parkinson’s , diabetes type II, polyglutamine and other triplet repeat expansion diseases, and depression, epilepsy and schizophrenia, to mention a few.
Our lab focuses on G-protein coupled receptors (GPCRs) and their neuropeptide ligands that regulate the function of the nervous system. GPCRs represent important targets for drug development but further research is necessary to understand what processes these receptors control.
Understanding what signaling molecules are being affected within the nervous system by a single GPCR mutation is our goal.
Aug 11, 2015 at 4:16 PM