Brian Perkins, Ph.D. Department of Molecular and Cellular Biology Harvard University 16 Divinity Ave. Cambridge, MA 02138 Tel.: (617) 495-2599 E-Mail: bperkins@fas.harvard.edu Sponsor John Dowling, Ph.D. dowling@fas.harvard.edu

"I feel honored to have been selected for this postdoctoral training program. I especially appreciate the opportunity to frequently interact with some of the most influential vision research scientists in the world. The training and mentoring the faculty provide will be very useful in planning a career in vision research."

My research is designed to utilize a vertebrate genetic system capable of identifying dominant mutations affecting the zebrafish retina, with particular emphasis on mutations involved in rhodopsin trafficking. The long-term objectives of the proposed research include the identification of genes associated with blindness caused by age-related retinal degeneration and the characterization of the cellular and molecular mechanisms underlying retinal degeneration. Mutations causing dominantly inherited night blindness will be isolated by a behavioral assay and confirmed by histological and physiological methods. Proper rhodopsin localization and transport will be evaluated by breeding mutant zebrafish with transgenic zebrafish that express a transgene encoding a rhodopsin-green fluorescent protein (GFP) fusion protein and examining the progeny by confocal fluorescent microscopy. Additional characterization of other transport systems within the photoreceptors of mutant fish will elucidate possible interactions between cellular transport mechanisms. Finally, identification of the genes responsible for these mutations will be achieved by positional cloning strategies. The proposed work will provide insight to the mechanisms underlying photoreceptor cell death that ultimately lead to retinal degeneration and blindness associated with aging.

Publications

Intody, Z*., Perkins, B.D*., Wilson, J.H., and Wensel, T.G. (2000) Nucleic Acids Research Blocking Transcription of the Human Rhodopsin Gene by Triplex-Mediated DNA Photocrosslinking. 28(21) 4283-4290.
*Authors contributed equally to this work.

Sargent, R.G., Meservey, J., Perkins, B.D., Kilburn, A.E., Intody, Z., Adair, G.M., Nairn, R.S., and Wilson, J.H. (2000) Nucleic Acids Research Role of the Nucleotide Excision Repair Gene ERCC1 in Removal of Nonhomologous Tails during Repair of Double-Strand Breaks in Mammalian Cells. 28(19) 3771-3778.

Perkins, B. D.,Wensel, T.G., Vasquez, K.M. and Wilson, J.H. (1999) Biochemistry Psoralen Photocrosslinking via Triplex Forming Oligonucleotides at Multiple Sites in the Human Rhodopsin Gene. 38(39) 12850-12859.

Perkins, B. D., Wilson, J.H., Wensel, T.G. and Vasquez, K.M. (1998) Biochemistry Triplex Targets in the Human Rhodopsin Gene. 37(32) 11315-11322.

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Last updated: November 8, 2002