| | Principal Investigators
| Benjamin H. White, Ph.D. |
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Dr. White received a B.A. in Physics and Mathematics from the University of Oregon (Honors College)
and a Ph.D. in the Neural Sciences from Washington University in St. Louis. His graduate work with
Jonathan Cohen focused on the structural basis of ion channel gating. Postdoctoral work with Leonard
Kaczmarek at the Yale University School of Medicine focused on mechanisms of calcium channel
modulation by PKC. While at Yale, Dr. White�s interests shifted to the potential use of ion channels to
investigate the neuronal substrates of behavior. Working between the Kaczmarek laboratory and the
laboratory of Haig Keshishian, he showed that a genetically modified Shaker K+ channel (called the
"Electrical Knock-Out," or EKO channel) could be used to inhibit the electrical activity of targeted cells
in Drosophila and that random expression of the EKO channel in Drosophila could be used to generate
behavioral deficits. Dr. White is currently the chief of the Unit on Neural Function in the Laboratory of
Molecular Biology. His laboratory is exploiting this observation to develop behavioral screens, analogous
to classic genetic screens, to identify the neurons underlying specific behaviors.
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| Research Interests |
While considerable progress has been made in understanding the molecular and cellular foundations of nervous system function, understanding the integrative activities that give rise to behavior is still far away. This is partly due to the lack of general tools for manipulating the activities of individual neurons or groups of neurons in living, behaving animals. In particular, tools that can suppress the activity of targeted neurons' and therefore establish the role of these neurons in individual behaviors—have only recently become available. These tools take the form of genes whose products block neuronal activity, either by blocking synaptic transmission or neuronal excitability, and which can be selectively expressed in subsets of neurons using cell-type specific promoters. The most compelling demonstration of the efficacy of these methods has been made in the fruit fly, where researchers have been able to take advantage of the Gal4-UAS system, a general method for cell-type specific—and more recently, temporally restricted--expression of genes of interest. In Drosophila, it is now possible to selectively turn off—and in some cases, turn back on—specific subsets of neurons in living, behaving animals.
Stimulated by the prospect of using such manipulations to identify and characterize the neuronal circuits
governing specific behaviors, the laboratory is currently pursuing twin interests. One approach is applying
existing tools for suppressing activity to analyze the neuronal circuitry underlying particular behaviors
(wing expansion and sleep) and visual processing; another approach attempts to develop further
molecular genetic tools for the targeted manipulation of neuronal activity that will be useful for future
studies. These include tools that enhance (rather than suppress) electrical activity, and tools that permit
more refined spatial and temporal patterns of gene expression than are currently obtainable with the
Gal4-UAS system. The lab is focusing on techniques that may be useful not only in Drosophila,
but also in vertebrates, where molecular genetic manipulation of neuronal activity in vivo has thus far been limited.
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| Representative Selected Recent Publications: |
- White, B.H., Osterwalder,
T.P., Yoon, K.S., Joiner, W.J., Whim, M.D., Kaczmarek,
L.K., and Keshishian, H.: Targeted Attenuation
of Electrical Activity in Drosophila Using a Genetically
Modified K+ Channel. Neuron, 31, 699-711, 2001.
- Osterwalder, T, Yoon, K.S. White, B.H., and Keshishian, H.:
A Conditional Tissue-Specific Transgene Expression
System using Inducible Gal4. Proc. Natl. Acad. Sci.
USA, 98, 12596-12601, 2001.
- White, B., Osterwalder,
T., and Keshishian, H.: Molecular Genetic
Approaches to the Targeted Suppression of Neuronal
Activity. Curr. Biol., 11, R1041-R1053, 2001.
- White B.H., Cummins
T.R., Wolf D.H., Waxman S.G., Russell D.S., Kaczmarek
L.K. : The HSV-1 Helper Virus 5dl1.2 Suppresses
Na+-Currents in Amplicon-transduced Neurons. J. Neurophysiol.,
87, 2149-57, 2002.
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