July 31, 2008 — Noelle Dwyer, a University of Virginia assistant professor of cell biology, is working to identify novel genes that are vital to brain development. A $50,000 Fund for Excellence in Science and Technology Distinguished Young Investigator grant will advance her promising research.
"The brain's development is very complicated and we're really just starting to understand how it works," Dwyer said. "It's still one of the big mysteries of science: How is the brain built? How does its structure mediate thoughts, decisions, and actions?"
Dwyer studies the cerebral cortex, the region of the brain that determines functions such as language, memory and sensory perception. Her goal is to understand how the structure of the brain is built during development and how the connections between different parts of the brain form. Dwyer focuses on the growth of the layers of the cortex and the connections between the cortex and a deeper structure called the thalamus. Proper development of these neuronal connections is essential because they serve as communications highways for messages to and from the cerebral cortex.
"The connections between the thalamus and the cortex mediate all of your conscious perceptions and actions, so your thoughts would be disconnected from your body if you didn't have these connections," said Dwyer. "We don't know for sure, but there is some evidence to suggest that there are problems with these connections in people with epilepsy, mental retardation, and possibly schizophrenia — perhaps related to defects in the way that the layer structure of the brain forms and in general brain growth."
Dwyer uses mouse genetics as a research approach. Prior to her appointment at the University of Virginia, she worked as a postdoctoral researcher in Chris Walsh's lab at Harvard Medical School. While there, Dwyer designed a unique forward genetics screen that enabled her to identify five mutant strains of mice with defects in brain formation. Forward genetics is a classical approach that begins by identifying a specific mutation and then conducting genetic mapping to pinpoint the location of the responsible gene. This method has traditionally been used in simpler animals like fruit flies, but has recently become easier in mice due to the mouse and human genome projects.
Dwyer's newly funded project will focus on the magoo mutant, a line of mice that doesn't survive past the embryonic stage because of limited neuron production — which leads to them having very small brains. Dwyer's genetic mapping of the magoo mutant identified a mutation in a kinesin motor protein. Since this particular gene is implicated both in brain development and cancer formation, her research could have significance for not only the treatment and prevention of seizure disorders and mental retardation, but also for cancer drug discovery.
Dwyer plans to conduct both in vivo and in vitro studies of the magoo brain and brain cells in order to get a full picture of both the cellular and systemic effects of this mutation. Citing her relationship with U.Va.'s Morphogenesis and Regenerative Medicine Institute, she explained, "We're really looking at these issues on multiple levels. Both within the Department of Cell Biology and other departments, we are trying to understand how changes in the structures of individual cells can cause changes in the shapes of whole tissues or whole organisms, whether during development, in a disease state, or during evolution."
The FEST Distinguished Young Investigator Grant Program is administered by the Office of the Vice President for Research and Graduate Studies and supports junior faculty research in the sciences, engineering and medicine.