Graduate Training in Neuroscience
University of Washington
Dana L. Miller
Assistant Professor, Department of Biochemistry
Animals must constantly monitor external conditions, sense relevant changes and integrate this information with physiology. Our goal is to understand how animals sense and adapt to changing environments. We use C. elegans as a model to investigate how environmental changes are integrated, working from the level of cellular responses through organism physiology and behavior. We are particularly interested in adaptations to changes in oxygen (O2). Decreased O2 availability is a major factor that contributes to cellular death resulting from heart attack and stroke. We are taking a genetic approach to define novel factors that can protect cells and tissues from decreased O2. We have found that in C. elegans, embryos suspend development and are protected from otherwise lethal hypoxia by an embryonic diapause, which is controlled by maternal neuronal factors. One project in the lab is to understand the perception of hypoxia in the adult neurons, and how this initiates a systemic response to influence developmental progression and survival. Another ongoing project in the lab is to develop a mechanistic understanding of how hypoxia alters cellular function. We have found that specific hypoxic concentrations of O2 can induce aggregation of polyglutamine (polyQ)-containing proteins. PolyQ protein aggregation is associated with at least seven devastating neurodegenerative diseases. We are working to develop a mechanistic understanding of how low O2 contributes to polyQ aggregation. Our recent work suggests that hydrogen sulfide (H2S) protects against hypoxia-induced polyQ aggregation. We are interested in understanding how hypoxia and H2S act to influence polyQ aggregation. This work will provide new insights into how to treat and prevent polyQ-induced neurodegeneration.
This is a epifluorescence image of two different C. elegans strains. In one strain, RFP is being expressed in the two bilaterally-symmetrical AIY interneurons (psuedocolored magenta). AIY neurons are important for integrating information from the environment into organism physiology. The other strain expressed YFP fused to a polyglutamine repeat in the body wall muscles (psuedocolored in green). As in a variety of neurodegenerative diseases, the polyglutamine repeats lead to the aggregation of the YFP that can be visualized as bright foci (pink/white). ( images were taken by Harley Childs and Jill Groulik).