About

We study the genetic pathways that enable neurons to reliably transfer information. Information is transferred by the controlled release of neurotransmitters, hormone-like molecules that act over very short distances and act on target cells such as other neurons or muscles. Abnormalities or dysfunction in this process can lead to neural disorders and disease. By resolving the molecular mechanisms that control the release of neurotransmitters in the model animal the roundworm C. elegans, we gain fundamental knowledge of how nervous systems work, and we gain practical knowledge that can lead to more effective drug therapies that target evolutionary conserved proteins between worms and humans.

Caenorhabditis elegans is a free-living (non-parasitic) soil roundworm widely used to study various aspects of biology. The whole animal is studied by different research groups at the molecular, cellular, organismal, ecological, and evolutionary levels.

There are several advantages for studying this simple creature.

First, the animal is amenable to genetic analysis. The animal easily grows and reproduces abundant progeny in the lab, it has a fast 3-day generation time, and the animal can be mated or allowed to self fertilize (the primary form is a hermaphrodite capble of producing eggs and its own sperm). These characteristics facilitate unbiased forward genetic screens that lead to gene discovery and resolution of genetic and associated biochemical pathways.

Second, molecular genetic tools are well established. A fully sequenced genome (completed in 1999, the first metazoan fully sequenced), well-established transgenic procedures, fluorescent gene reporters (see below), and optimized CRISPR/Cas9 gene editing protocols enable the researcher to experimetnally modify genes to investigate temporal and spatial gene expression or investigate structure-function relationships of encoded gene products.

Third, the animal has transparent skin. Different cell types are easily observed under dissecting and compound light microscopes in living individuals. The use of transgenic green fluoresencent protein and its derivatives allow the visualization and analysis of gene expression, under the control for endogenous gene promoters, in living indiviudals. Translational fusions between GFP and a protein of interest allow proteins to be tracked in living cells in the whole animal. Genetically encoded fluoresecent sensors for pH or calcium ion concentration permit the real-time observation of cell physiology in whole behaving animals.

Fourth, the neuronanatomy is fully mapped at the ultrastructural level. The adult has 302 neurons, the neurons develop and position themselves with an invariant, identifiable position. Neuronal connectivity is fully mapped  from serial electron microscope reconstructions.

Fifth, and perhaps most importantly, the community is awesome. From early on of its founding in the early 1970’s, members have been committed to cooperative sharing of materials and procedures, building community-wide tools, and training the next generation of scientists. Conferences are beloved and include the sharing of C. elegans inspired art and have been know to include a worm comedy show.