Genetic analysis of neural circuits
My lab studies somatosensory neural circuit organization and information processing in Drosophila using optogenetic approaches.
How sensory information is processed by the nervous system to produce behavioral outputs is a long-standing problem in neuroscience, but one far from being understood. My lab exploits the many advantages of the Drosophila model system to study the relationship between somatosensory input and behavior. Our overall strategy is to first map neural circuits associated with specific somatosensory neurons and then manipulate and measure neuronal activity within the circuit to elucidate the fundamental principles of neuronal circuit logic.
Since the depth with which a neural circuit will be understood will correlate with the precision with which it can be manipulated, we are generating fly strains containing enhancers specific for sensory neurons, each type of neurotransmitter, and each type of neurotransmitter receptor. These valuable tools will allow us to express transgenes for manipulating and measuring neuronal activity in small subsets of neurons in an intact animal. Connections between neurons are being mapped using a recently developed method in which Green Fluorescent Protein (GFP) is split in two and its separate parts expressed independently in neuronal subsets using these specific enhancers. Synaptic connections between specific neurons are confirmed where GFP is functionally "reconstituted" and observed as green fluorescence. These same enhancers are being used to drive expression of excitatory and inhibitory light-gated ion channels in small subsets of neurons. Expression of the excitatory channel Channelrhodopsin2 in sensory neuron subsets allows larval behavior to be controlled with light. As enhancers that allow expression in neurons downstream of the sensory neurons are generated, expression of the excitatory and inhibitory light-gated channels will enable a determination of neurons that are necessary and sufficient to trigger given behavioral responses. As a given neural circuit becomes more defined, neuronal subset-specific enhancers will be used yet again to express genetically-encoded calcium indicators to allow optical measurements of neuronal activity. Longer term, once multiple neural circuits are mapped, studies will be initiated to work out how distinct neural circuits compete with, enhance, or otherwise interact with each other as this is more realistic approximation of what occurs in natural world.
Stowers, R.S. and Isacoff, E.Y. Drosophila HIP14 is a presynaptic protein required for photoreceptor synaptic transmission and expression of the palmitoylated proteins SNAP-25 and CSP. J. NEUROSCIENCE 2007 27:12874-83.
Glater, E.E., Megeath, L.J., Stowers, R.S., and Schwarz, T.L. Axonal transport of mitochondria requires Milton to recruit kinesin heavy chain and is light chain independent. J. CELL BIOLOGY 2006 173:545-57.
Stowers, R.S*., Babcock, M*, Leither, J., Goodman, C.S. and Pallanck, L.S. "A genetic screen for synaptic transmission mutants mapping to the right arm of chromosome 3 in Drosophila" GENETICS 2003 165:171-183 *authors contributed equally to this work.
Stowers, R.S., Megeath, L.J., Andrzejak, J.G., Meinertzhagen, I.A., and Schwarz, T.L. "Axonal transport of mitochondria to synapses depends on Milton, a novel Drosophila protein" NEURON 2002 36:1063-1077.
BIOH 320 Biomedical Genetics
-- Introduction to fundamental principles of eukaryotic molecular genetics. Emphasis on the genetics of the major model organisms of biomedical research and how they are exploited to understand human biology and disease.
BIOH 455 Molecular Medicine
-- Lecture and seminar course based on recent, original papers. Moves from human disease to molecular explanations. Intended for upper level students with a strong background in biology.
EducationB.S. Mathematics, Southern Methodist University, 1987.
Ph.D. Biochemistry, Stanford University School of Medicine, 1997.