Department of Cell & Structural Biology
Ph.D. (1985) Rockefeller University
Research Topics
Research Interests
The nervous system and the genome are the two major control systems in complex biological organisms. My research is directed at the interface between the two.
Some of our studies examine the role of gene regulation in the development of specific neural circuits in the brain. We established a tissue culture model of circuit development, based on the formation of the motor pathway responsible for song production in male zebra finches. We discovered that the male pattern of pathway development is triggered by estrogens, which are produced at high levels in the developing male brain. We now would like to identify the control mechanisms responsible for the male pattern of brain estrogen production. We would also like to identify the presumed genomic targets which respond to estrogen and promote song pathway maturation.
Other studies examine the influence of dynamic gene regulation on the storage and retrieval of information (memories) in the adult brain. Our prior work in songbirds showed that novel or salient experiences activate a pattern of gene expression in parts of the brain involved in processing the relevant information. More recently we found evidence that this genomic response promotes the storage of memories or associations during the following hour. We would now like to develop a more complete description of this genomic and proteomic response, and understand how it is recruited, suppressed and directed to specific brain systems during normal experience.
The future aims described above will all benefit by application of new and rapidly developing technologies for genomic research, including high-throughput sequencing, EST database development, and microarray analyses of gene expression. We are the center of a multi-institutional, NIH-funded effort to produce a zebra finch brain EST collection, standardized microarray and whole genome sequence. In another collaborative project at the Beckman Institute we are exploring the application of novel optical methodologies for monitoring of neurophysiologic (and possibly genomic) activities in behaving animals. Our work is relevant to a broad range of issues in brain science, and has been supported by three of NIH institutes (Aging; Mental Health; Neurological Disorders and Stroke) and the National Parkinson Foundation, among others.
Key Words
Recombinant
DNA, Introduction of DNA into Animal Cells, Gene Expression Systems, Molecular
Evolution, Protein-protein interaction, Molecular systematics, Supramolecular
systems, Protein Biotechnology, Site-directed Mutagenesis, Membrane structure
and function, Protein purification and characterization, Molecular Modeling,
Structural Biology, Mass spectrometry, Fluorescence spectroscopy and/or
microscopy, Gas and/or Liquid chromatography, Disease models, Hormones, Animal
cell and/or tissue culture, Neurobiology, Transgenic animals, Fluorescence
spectroscopy and/or microscopy, Phylogenetic, Molecular Evolution, Hight Throughtput Sequencing Process, Contig Assembly Genome Annotation, Data Clustering (microarray)
Data Mining and Visualization
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