Potier, Beth

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University of New HampshireUniversity of New Hampshire Scholars' RepositoryMedia Relations Administrative Offices7-16-2006$1.4 Million Grant Helps Professor See The LightBeth PotierFollow this and additional works at: https://scholars.unh.edu/newsThis News Article is brought to you for free and open access by the Administrative Offices at University of New Hampshire Scholars' Repository. It hasbeen accepted for inclusion in Media Relations by an authorized administrator of University of New Hampshire Scholars' Repository. For moreinformation, please contact nicole.hentz@unh.edu.Recommended CitationPotier, Beth, "$1.4 Million Grant Helps Professor See The Light" (2006). UNH Today. 964.https://scholars.unh.edu/news/9649/18/17, 12)17 PM$1.4 Million Grant Helps Professor See The LightPage 1 of 2http://www.unh.edu/delete/news/cj_nr/2006/july/bp_060717light.cfm@type=n.html $1.4 Million Grant Helps Professor See The LightContact:  Beth Potier 603-862-1566UNH Media RelationsJuly 17, 2006DURHAM, N.H. -- University of New Hampshire professor Rick Cote has received $1.4 millionfrom the National Institutes of Health (NIH) to continue research into the central enzyme thatcontrols initial steps of vision and that, when defective, can result in retinitis pigmentosa, aleading inherited cause of blindness.Retinitis pigmentosa, or RP, affects 1.5 million people worldwide. Typically, symptoms begin inchildhood or early adulthood and progress from impairments in night vision to tunnel vision.The degree of vision loss varies, but in some cases RP leads to total blindness.Cote, a professor of biochemistry and molecular biology who has received NIH fundingthrough the National Eye Institute for 18 years, conducts fundamental research into visualsignaling pathways in the photoreceptors of the retina. “Until you know how the retinafunctions normally, you’re not going to be able to understand how genetic or environmentaldefects in the visual pathway can cause vision loss or total blindness, or how to slow orprevent disease progression,” he says.Normal functioning of the retina begins with light being absorbed by the photoreceptor cells,called rods and cones. Cones are responsible for color perception, daylight vision, and visualdiscrimination tasks like reading, while rods provide peripheral vision and vision in low light.Central to rod and cone visual signaling is the phosphodiesterase (PDE) protein. This enzymeis activated by light and is directly responsible for the nerve impulse that signals theperception of light. “It’s therefore not surprising that this exquisitely light-sensitive enzymecan also cause retinal disease when its regulation or catalytic activity is impaired by a geneticmutation, as in certain forms of RP,” says Cote. Most of Cote’s research career has focused onbetter understanding how PDE functions. With such knowledge, he says, “we might somedaybe able to intervene therapeutically to prevent defects in PDE from causing retinal disease.”Working with graduate and undergraduate students in his lab, along with three full-timeresearch scientists, Cote uses a variety of molecular, biochemical, cell biological andpharmacological approaches to understand the structure of PDE and how it is regulated indarkness and in the light. This latest four-year NIH award will support several new directionsin Cote’s research program. One project involves a collaboration with Tom Laue, professor ofbiochemistry and molecular biology, to use novel biophysical techniques to determine howsmall molecules and proteins bind to PDE and alter its structure and regulatory properties.In another strand of his research, conducted in partnership with Karen Carleton, researchassociate professor with UNH’s Hubbard Center for Genome Studies, Cote is exploring theevolution of vertebrate rod and cone cells in the retina. By focusing on the evolution of the9/18/17, 12)17 PM$1.4 Million Grant Helps Professor See The LightPage 2 of 2http://www.unh.edu/delete/news/cj_nr/2006/july/bp_060717light.cfm@type=n.htmlPDE protein, Cote and Carleton hope to better understand its functioning – and malfunctioning– in humans. “The basic plan for the human retina evolved at the time when vertebratesevolved from the invertebrates,” he says. In their preliminary work, Cote and Carleton haveidentified rod and cone photoreceptor PDE in species ranging from fish to humans, and theiramino acid sequences are very similar.Yet another line of work is to evaluate a newly discovered PDE binding protein (called GARP2)for its potential to turn off the PDE in rods during daytime – “rods are so light-sensitive thatthey can’t function in bright light,” Cote says – to conserve metabolic energy.Cote is also exploring PDE’s sexier side: its relationship to Viagra and other drugs that treaterectile dysfunction. Of the 11 families of phosphodiesterases, the photoreceptor PDE –named PDE6 – is most closely related to PDE5, an enzyme abundant in smooth muscle tissuein our bodies. Viagra and similar drugs (Levitra, Cialis) work by inhibiting PDE5, but most ofthese drugs also potently inhibit PDE6, causing temporary alterations in vision. A betterunderstanding of the differences between PDE5 and 6 will result in creating drugs thatselectively target PDE5 but do not affect PDE6 or the visual process. While Cote does notforesee an immediate role for these drugs in combating retinal diseases, PDE inhibitors haveprofound therapeutic potential in treating cardiovascular disease, asthma, diabetes, andcancer, making the development of PDE inhibitors with no adverse effects on vision verydesirable.After two decades of research on PDE, Cote remains fascinated with how rods and cones, andthe proteins contained within these light-detecting cells, translate light into sight. “The activityof all these photoreceptor proteins – especially PDE - have to be coordinated on themillisecond time scale so we can see. It’s a miracle that it all works,” he says.Rick Cote can be reached at rick.cote@unh.edu or 603-862-2458. For more detailedinformation on Cote’s research, visit www.cote.unh.edu.[an error occurred while processing this directive]

$1.4 Million Grant Helps Professor See The Light

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$1.4 Million Grant Helps Professor See The Light

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