Department of Biological Sciences
241 Life Sciences Research Facility
Office Phone: 740-597-1921
Lab Phone: 740-597-1923
Participate in: BIOS 326: Laboratory Genetics
MCB 670: Current Topics in Molecular and Cellular Neurobiology
MCB 710: Advanced Signal Transduction
MCB 760: Advanced Cell Biology
Tutorial Topics: Neuronal development and function, neurodegenerative diseases, monoamines signaling, mRNA localization and cell polarity, research in C. elegans.
Left to right:
Ashley Predmore LindseyGallaugher
Nathan Kuhn Jessye Rhominski
Nanda Filkin Melissa LaBonty
BACKGROUND: The research in our laboratory uses a model organism, the small soil nematode Caenorhabditis elegans, to examine the development and function of the nervous system. Our main interests are in the genetics of regulation in the nervous system and how the resultant neuronal architecture leads to normal neuronal function and behavior. C. elegans is a wonderful organism for studying the nervous system. It is a very simple animal: the adult hermaphrodite has 959 somatic cells, including 302 neurons, with known origin, development, and connectivity. C. elegans are small (1 mm long), transparent, non-obligate hermaphrodites with a short generation time. They have a malleable genome with 22,025 sequenced genes. There are thousands of mutants, including many with severe neural defects, and transgenic animals may be generated rapidly. These properties have allowed us and others to study the roles of many different proteins and genes in the nervous system.
Cholinergic neurons labeled with GFP in a living C. elegans
CURRENT RESEARCH: Our research uses a variety of techniques, including genetics, molecular biology, cell biology, and behavioral assays, to examine the development, distribution, and function of proteins that are necessary for neurotransmission. In C. elegans, as in humans, the neurotransmitter acetylcholine is used at excitatory neuromuscular junctions and is essential for viability. We are examining the regulation and function of two cholinergic proteins, ChAT (the synthetic enzyme choline acetyltransferase) and VAChT (the vesicular acetylcholine transporter), in controlling neurotransmission and behavior.
We are also using mutant analysis to study monoamine neurotransmitters in this simple animal. In humans, monoamines are important modulatory neurotransmitters; proteins that alter the uptake and release of monoamines are targets of several psychoactive drugs. Monoamines are also important for the modulation of specific behaviors in C. elegans, including responses to food and egg-laying. We are studying several genes that are required for normal monoamine levels, including the vesicular monoamine transporter, the dopamine plasma membrane transporter, the dopamine synthetic enzyme, and putative monoamine degradation enzymes. In particular, we are interested in how acute and chronic changes in these proteins alter monoamine-dependent behaviors and sensitivity to monoamines. What short-term or developmental changes or compensation occur when dopamine synthesis, release, re-uptake, or degradation is perturbed?
C. elegans labeled with antibodies to a cholinergic protein (green = vesicular acetylcholine transporter) and a monoaminergic protein (red = vesicular monoaminergic transporter). The proteins are present in several regions of the nervous system, including the nerve ring (NR), nerve cords (DNC, VNC), pharynx (ph) and smaller neuronal processes (subs).
Panel A: Antibody staining shows cholinergic (green) and monoaminergic (red) synapses in the head a normal hermaphrodite.
Panel B: Diagram including neuronal somas (white circles) and processes (black lines) in an adult head.
Panel C: shows the synapses in a mutant, unc-104, that has defects in synaptic vesicle transport.
A new line of research is directed at understanding the importance of localized protein synthesis in neuronal function. Regulation of the subcellular localization of particular mRNAs has been identified as a critical step in the control of local protein levels and polarity in many cells, including neurons. We are adapting a GFP-mRNA labeling technique to living C. elegans to identify genes and proteins that are important for the regulation of mRNA localization and transcription. The studies will increase our understanding of the complex processes that polarity in animals.
Duerr, JS, HP Han, SD Field, JB Rand (2008) Identification of major classes of cholinergic neurons in the nematode Caenorhabditis elegans. J Comp Neurology 506:398-408. http://www3.interscience.wiley.com/journal/117351471/issue
Mathews, EA GP Mullen, JA Crowell, JS Duerr, JR McManus, A Duke, J Gaskin, and JB Rand (2007) C. elegans snt-1 Mutants Affecting Synaptotagmin Isoform Expression and Localization. Mol Cell Neurosci. 34(4):642-52. http://www.sciencedirect.com/science/journal/10447431
Duerr, J.S. (2006) Immunohistochemistry. In WormBook, ed. The C. elegans Research Community. 61p. doi/10.1895/wormbook.1.105.1, http://www.wormbook.org/
Sandoval, G.M., J.S. Duerr, J. Hodgkin, J.B. Rand, and G. Ruvkun (2006) An interaction between the vesicular acetylcholine transporter VAChT/UNC-17 and synaptobrevin/SNB-1 in C. elegans. Nature Neuroscience 9: 599-601. http://www.nature.com/neuro/journal/v9/n5/abs/nn1685.html
Duerr, J.S., J. Gaskin, and J.B. Rand (2001) Identified neurons in C. elegans coexpress vesicular transporters for acetylcholine and monoamines, Am. J. Physiol Cell Physiol. 280:C1616-C1622. http://ajpcell.physiology.org/cgi/content/full/280/6/C1616
Zhu, H., J.S. Duerr, H. Varoqui, J.R. McManus, J.B. Rand, and J.D. Erickson (2001) Analysis of point mutants in the Caenorhabditis elegans vesicular acetylcholine transporter reveals domains involved in substrate translocation, J. Biol. Chem. 276:41580-41587.
Lickteig, K.M., J.S. Duerr, D.L. Frisby, D.H. Hall, J.B. Rand, and D.M. Miller III (2001) Regulation of neurotransmitter vesicles by the homeodomain protein UNC-4 and its transcriptional co-repressor UNC-37/Groucho in Caenorhabditis elegans cholinergic motor neurons, J. Neurosci. 21:2001-2014. http://www.jneurosci.org/cgi/content/full/21/6/2001
Kohn, R.E., J.S. Duerr, J.R. McManus, A. Duke, T.L. Rakow, H. Maruyama, G. Moulder, I. Maruyama, R.J. Barstead, and J.B. Rand (2000) Expression of multiple UNC-13 proteins in the C. elegans nervous system, Mol. Bio. Cell. 11:3441-3452. http://www.molbiolcell.org/cgi/content/full/11/10/3441
Duerr, J.S., D.L. Frisby, J. Gaskin, A. Duke, K. Asermely, D. Huddleston, L.E. Eiden, and J.B. Rand (1999) The cat-1 gene of Caenorhabditis elegans encodes a vesicular monoamine transporter required for specific monoamine-dependent behaviors, J. Neurosci. 1:72-84. http://www.jneurosci.org/cgi/content/full/19/1/72
Filkin N., J. Rhominski, A. Sauer, J. Russell, and J.S. Duerr. Interactions of mutations in the vesicular monoamine transporter and monoamine synthesis mutants in C. elegans.
Sandoval, G.M., J.S. Duerr, J. Hodgkin, J.B. Rand, and G. Ruvkun (in prep.) Transmembrane domain-mediated interactions between the vesicular acetylcholine transporter VAChT/UNC-17 and synaptobrevin/SNB-1 in C. elegans.