|Daniel L. Chase
Assistant Professor of Biochemistry and Molecular Biology, University of Massachusetts
Ph.D.: University of New Hampshire, Durham
Cellular and Molecular Mechanisms of Neurotransmitter Signaling
The focus of my laboratory is to understand how the neurotransmitter dopamine modulates the activities of neurons. Dopamine signaling is involved in learning and memory and abnormal dopamine signaling has been implicated in a variety of mental disorders including schizophrenia, drug addiction, and Parkinson’s disease. Despite the importance of understanding how dopamine affects brain function, we do not have a clear understanding of the signaling mechanisms through which dopamine acts. This lack of understanding is in large part due to the inability to identify the molecular components involved in dopamine signaling. Biochemical approaches to identify such components are hampered by the cellular heterogeneity of the brain, by the difficulty in preparing large, pure populations of primary neurons and by the lack of cell lines that can be cultured and that accurately reflect the cellular environment present in neurons.
Like mammals, the nematode C. elegans uses dopamine to modulate the activities of neurons. We use genetic screens in C. elegans to isolate mutants defective in dopamine signaling and these mutants identify the molecular components through which dopamine acts. We have recently identified several genes that encode novel dopamine signaling components. We plan to characterize these new signaling components using a combination of genetic, behavioral, imaging, and biochemical approaches. We then plan to test whether these components are conserved and serving similar roles in the brain.
Several features of C. elegans including the fact that animals are transparent and can stably express trangenes help us to understand how and where dopamine acts. Shown is a fluorescent image of an animal carrying integrated transgenes that express a green fluorescent protein (GFP) from the D1-like dopamine receptor (dop-1) promoter and a red fluorescent protein (RFP) from the D2-like dopamine receptor (dop-3) promoter. dop-1::GFP is expressed in the support cells of the head (bracket 1) and both dop-1::GFP and dop-3::RFP are expressed in neurons of the head (bracket 2), tail(bracket 3), and ventral cord (bracket 4).
1. Dong M-Q., Chase D.L., Patikoglou G.A., & Koelle, M.R. Multiple RGS proteins alter neural G protein signaling to allow C. elegans to rapidly change behavior when fed. Genes and Dev.14: 235-243. (2000).
2. Chase, D.L., Patikoglou, G.A., & Koelle, M.R. RGS proteins that inhibit G-alpha o and G-alpha q signaling in C. elegans neurons require a G-beta5-like subunit for function. Current Biology11:, 222-231. (2001).
3. Chase, D.L., & Koelle, M.R. Genetic analysis of RGS protein function in C. elegans. Methods in Enzymology. 389: 305-320. (2004).
4. Chase, D.L., Pepper, J.S., & Koelle, M.R. Mechanism of extrasynaptic dopamine signaling in C. elegans. Nat. Neurosci.7: 1096-1103. (2004).