Creative. Stubborn. Tireless. Clever. That's how Julie Simpson's academic mentors describe her. During her postdoctoral research, Simpson built new tools to alter activity in different brain regions of the fruit fly, Drosophila melanogaster. She has identified neurons that contribute to a range of motor behavior defects, such as seizures and paralysis. Moreover, she has generated roughly 350 new fly lines that allow controlled gene expression in different groups of cells—enough to begin mapping a vast number of neurons, chart their changes, and explain their control over key behaviors.
Yet, Simpson uses a different word to describe herself: lucky. "I'm so lucky to have been here, studying anatomical neurocircuitry at this time, just as Janelia Farm takes shape," she says. "I have an unbeatable opportunity to get in on the ground floor at Janelia."
Simpson has a clear vision for her lab. Ultimately, her goal is to investigate how genes, neurons, and neural circuits contribute to particular behaviors. Her bottom-up approach to dissecting behavior begins with the most basic components of neural machinery. Eventually, by mapping brain structures to their behavioral outputs, she hopes to contribute to understanding the logic of neural organization—and its role in both normal learning processes and disease.
As a postdoctoral fellow, Simpson laid the groundwork for this ambitious agenda. Her goal was to map the anatomy of a neural circuit responsible for motor control and then to manipulate the neurons involved, testing the effect on behavior. To do so, she generated more than 350 Drosophila lines, carefully designed to drive expression of desired target genes in selected regions of the central nervous system, and more recently, she has generated a similar number of lines to restrict gene expression to smaller numbers of neurons. She also adapted and developed tools to acutely and reversibly excite or dampen the activity of those neurons.
With these tools, Simpson conducted behavioral screens that indicated certain clusters of neurons—for instance, glutamatergic motor neurons and subsets of sensory neurons—affect motor behavior. She has crafted a preliminary map of neurons capable of initiating seizures, paralysis, and related loss of motor control. This work is ongoing.
"It has become very clear that better imaging approaches would help identify small groups of critical neurons and that more precise, quantitative ways to measure behavior will further the mapping effort," Simpson says. She hopes to use additional genetic techniques to refine the preliminary maps, develop different ways to change neural activity, and eventually design a way to trace connected circuits. "The scientific and technical resources at Janelia make it the perfect place for these experiments," she adds.
Simpson arrives at Janelia Farm with a stack of slide cases, 800 fly stocks—and lots of energy. The biggest draw, she says, is the people. "Neural circuit analysis and imaging require expertise in many areas, and the people coming to Janelia are ideal colleagues—because of their excellent science and their willingness to share knowledge," Simpson says. "We're all working on our independent research programs, but I'm confident our projects will overlap in synergistic ways."
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RESEARCH ABSTRACT SUMMARY:
To understand general principles of brain function and organization, Julie Simpson maps neural circuits in the adult fly brain that govern distinct motor behaviors. Her lab uses a range of genetic, neurobiological, and histological techniques to attack this problem at several levels—from genes and neurons to circuits and behavior.
Photo: Paul Fetters
