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3258 TAMU Office: Lab: Fax: 979-845-2891 |
Biography |
| Brian Perkins was born in Abilene, Texas and was educated in the public school systems of Weatherford, Texas and Edmond, Oklahoma. He received his B.S. degree in Biochemistry from Abilene Christian University in 1995. He earned his Ph.D. in Biochemistry and Molecular Biology from Baylor College of Medicine in 2000. His dissertation research in the laboratories of John Wilson and Ted Wensel focused on the use of oligonucleotides-based technologies for genetic modification of the human rhodopsin gene. He then did postdoctoral work with John Dowling at Harvard University from 2000-2004. While at Harvard, he began to explore the genetics of photoreceptor development and degeneration by using zebrafish as a model organism. By utilizing existing zebrafish mutants and performing a genetic screen for cell-specific mutations in the retina using transgenic zebrafish, Dr. Perkins laboratory is interested in understanding the genes required for photoreceptor development and maintenance. He will join the faculty of Texas A&M in the fall of 2004. | |
| Genetic Studies of Retinal Development in Vertebrates | |
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We are also studying the process of photoreceptor outer segment formation. To make an outer segment, microtubules and specific proteins must be transported to the basal body to form a cilium. This structure will extend and become filled with membrane disks to become an outer segment. A key part of this process requires the Intraflagellar Transport (IFT) pathway. Mutations in a multi-protein complex, the IFT particle, disrupt outer segment formation. A model for how IFT functions is presented below.
Proteins destined for the outer segment, such as rhodopsin, are transported from the Golgi to the base of the cilium where they are bound by the IFT particle. Through interactions with kinesin-II, the IFT particle then transports the protein cargo through the connecting cilium and to the outer segment, where the cargo is then incorporated into disk membranes. We are investigating mutations in three separate zebrafish IFT genes, IFT57, IFT88, and IFT172. These mutations prevent normal transport to the outer segment and the mutants exhibit defects in the development of photoreceptors and other ciliated cell types. Further investigations into this process will provide insight to a number of diseases that affect ciliated cells, such as Bardet-Biedl Syndrome, Senor-Loken Syndrome, and Polycystic Kidney Disease. |
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| Selected Publications | |
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Lunt, S. C., Haynes, T, and Perkins, B. D. Hedgehog signaling is not affected in zebrafish intraflagellar transport mutants. (Submitted) Seth W. Coleman, S. W., Perkins, B. D., Rosenthal, G. G., Sensory dysfunction in photopic but not scotopic vision in natural hybrids (Submitted) Sukumaran, S. and Perkins, B. D. (in press) Early Defects in Photoreceptor Outer Segment Morphogenesis in Zebrafish ift57, ift88, and ift172 Intraflagellar Transport Mutants. Vision Research Krock, B. L., and Perkins, B. D. (2008) IFT57 is Necessary for Photoreceptor Outer Segment Maintenance and Kinesin II Dissociation from the IFT Particle. Journal of Cell Science. 121(11):1907-1915. *Selected as a recommended paper for Faculty of 1000 Biology Insinna, C., Pathak, N., Perkins, B. D., Drummond, I., and Besharse, J. C. (2008) The homodimeric kinesin, Kif17, is essential for vertebrate photoreceptor sensory outer segment development. Developmental Biology. 316, 160-170 Gross, J. M., and Perkins, B. D. (2008) Zebrafish Mutants as Models for Congenital Ocular Disorders in Humans. Molecular Reproduction and Development. 75(3):547-555. Krock, B. L., Bilotta, J., and Perkins, B. D. (2007) Noncell-autonomous photoreceptor degeneration in a zebrafish model of choroideremia. Proc. Natl. Acad. Sci. U.S.A. 104(11):4600-4605. Perkins, B. D., Nicholas, C. S., Baye, L., Link, B. A., and Dowling, J. D. (2005) The dazed gene is necessary for late cell type development and retinal cell maintenance in the zebrafish retina. Developmental Dynamics, 233(2):680-694 Gross, J., Perkins, B. D., Amsterdam, A., Egana, A., Darland, T., Matsui, J., Sciascia, S., Hopkins, N., and Dowling, J. D. (2005) Mutations affecting vertebrate eye development identified by insertional mutagenesis in zebrafish. Genetics, Epub Feb 16. Perkins, B. D., Fadool, J. M., and Dowling, J. D. Analysis of photoreceptor development using transgenic zebrafish. Methods in Cell Biology. Zebrafish: Cellular and Developmental Biology 2nd Ed. Editors: Detrich H. W., Westerfield, M. and Zon, L. Koeller, K.M., Haggarty, S.J., Perkins, B. D., Leykin, I., Wong, J.C., Wong, W.H., Dowling, J.E., and Schreiber, S.L. (2003) Chemical genetic modifier screens: small molecule trichostatin suppressors as probes of acetylation in transcription, cell cycle progression, and stability of the cytoskeleton. Chemistry and Biology 10(5)397-410. Perkins, B. D., Kainz, P.M., O’Malley, D.M., and Dowling, J.E. (2002) Transgenic Expression of a GFP-Rhodopsin COOH-Terminal Fusion Protein in Zebrafish Rod Photoreceptors. Visual Neuroscience 19(3) 257-264. Intody, Z., Perkins, B. D., Wilson, J.H., and Wensel, T.G. (2000) Blocking Transcription of the Human Rhodopsin Gene by Triplex-Mediated DNA Photocrosslinking. Nucleic Acids Research 28(21) 4283-4290. Perkins, B. D., Wensel, T.G., Vasquez, K.M. and Wilson, J.H. (1999) Psoralen Photocrosslinking via Triplex Forming Oligonucleotides at Multiple Sites in the Human Rhodopsin Gene. Biochemistry 38(39) 12850-12859. Perkins, B. D., Wilson, J.H., Wensel, T.G. and Vasquez, K.M. (1998) Triplex Targets in the Human Rhodopsin Gene. Biochemistry 37(32) 11315-11322. |
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Brian Perkins studies the development of the vertebrate retina. The retina of a zebrafish is very similar to that of humans in both structure and function, so the genes required to make a zebrafish retina should be the same ones needed to make a human retina. To better understand the processes involved, Dr. Perkins looks for mutant zebrafish that have abnormal retinas. To facilitate this, transgenic zebrafish that make green fluorescence protein in the rod photoreceptors have been integrated into the genetic screens for mutants. This picture shows a normal (top) and mutant (bottom) zebrafish. The mutant does not have as many rod photoreceptors (cells in green) and has smaller eyes but the rest of the fish is normal. Future work on this and other mutants will help identify genes required for normal retinal development and will likely have relevance to human blindness disorders such as macular degeneration and retinitis pigmentosa.