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NIH awards researcher $1.5 million 'new innovator' grant for fruit-fly studies of prion proteins

GALVESTON, Texas -- The National Institutes of Health has selected University of Texas Medical Branch at Galveston (UTMB) Assistant Professor of Neurology Pedro Fernandez-Funez to receive a five-year, $1.5 million NIH Directors New Innovator Award.

NIH Director Dr. Elias Zerhouni will officially announce the 29 recipients of the grants, designed to foster young biomedical researchers with bold new ideas, at a symposium at NIH headquarters Wednesday, Sept. 19.

Fernandez-Funez, one of only three Texas scientists selected to receive one of the awards, won his grant with an original proposal to study prion diseases a group of deadly, brain-destroying disorders that include mad cow disease and its human version, Creutzfeldt-Jakob disease using genetically modified fruit flies and laboratory mice.

I was totally surprised when they notified me of the award the competition was very tough, Fernandez-Funez said. After the initial shock came tremendous joy for the recognition of the work were doing in the lab. This award will provide us with the financial means and stability to continue our innovative approach to understanding how prion proteins cause brain disease, and complement our parallel work on Alzheimers disease, which involves different proteins misbehaving in a similar way.

UTMB neurology department chairman Dr. Tetsuo Ashizawa applauded Fernandez-Funezs success in garnering the highly prestigious award.

For young investigators who have been trying hard to get over the final barrier of obtaining NIH funding, this is very encouraging news, Ashizawa said. It is also great news for UTMB and our School of Medicine, which has been making a special effort to provide support for young investigators, a critical element for the successful growth of the our next generation of scientists.

Fernandez-Funez and UTMB Assistant Professor Diego Rincon-Limas have been working closely together for four years using fruit flies to study human neurological disorders. Because its far easier to genetically manipulate and crossbreed the short-lived flies than laboratory mice, Fernandez-Funez said, they provide an ideal laboratory animal in which to quickly study the effects of many different proteins involved in neurodegenerative diseases on the nervous systems of living creatures.

A fly is like a test tube, but its alive, Fernandez-Funez said. Its a system where you can play with genes quickly and easily, so instead of doing one experiment in one year, you can do five or 10 or 15. If you fail in most of them, thats not really important whats important is that you find one of them that works.

Fernandez-Funezs NIH award funds experiments with fruit flies whose DNA has been genetically modified to produce hamster prion protein. In rodents, cows, humans and other mammals, such proteins can accidentally misfold, taking on an abnormal shape that causes other prion proteins they contact to take a similar shape one that promotes the accumulation of brain-cell killing protein deposits. And by the end of the transgenic fruit flies 40-day lifespan, their tiny brains also show the telltale signs of prion misfolding and neurotoxicity, according to Fernandez-Funez.

Weve produced these flies, we see the biochemical changes on the prion protein and we can see the neurodegeneration, Fernandez-Funez said. Now, we want to figure out how we can stop this process.

Using the new NIH funding, Fernandez-Funez and Rincon-Limas plan to investigate the protective effects in flies, mammalian cells and mice of so-called chaperone proteins, which work to make sure that other proteins take on their proper shapes after they are produced. Their preliminary experiments show that one such protein, known as Hsp70, protects their flies against the neurotoxic effects of prion protein misfolding; they intend to use their flies to determine whether other possibly protective chaperone proteins work as well. Next, theyll check any promising leads with experiments in mammalian cell cultures. Then, in experiments with both transgenic and normal mice in collaboration with Claudio Soto, also a UTMB professor and director of the university's George and Cynthia Mitchell Center for Neurodegenerative Diseases, theyll test whether they can extend such protection to mammals, both with genetic engineering and compounds that induce the production of chaperones.

By doing the groundwork in flies, we think we can find many new mechanisms of prion neurotoxicity, Fernandez-Funez said. The idea is that were going to keep looking for new ways of attacking the disease through all these new genes and proteins and pathways.


Contact: Jim Kelly
University of Texas Medical Branch at Galveston

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