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Latest discoveries at Salk Institute fuel new scientific questions

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Situated high above the bluffs in Torrey Pines and overlooking the Pacific Ocean, the Salk Institute was founded in 1960 as a place where some of the world's brightest minds would come together for the common goal of scientific discovery.

Its 59 faculty members, including three resident Nobel Laureates, have kept founder Dr. Jonas Salk's vision alive by contributing seminal breakthroughs in basic biological research in three general areas of science: Molecular Biology and Genetics; Neurosciences; and Plant Biology. Their discoveries have continued to provide clues toward better understanding the molecular origins behind some of today's most devastating disease, including cancer, AIDS/HIV, Alzheimer's and other neurodegenerative diseases.

Some of the most recent discoveries have provided insight into the underpinnings of Alzheimer's disease, a condition that riddles the brain with debilitating beta amyloid plaques and neurofibrillary tangles. A study by Andrew Dillin, an associate professor in the Molecular and Cell Biology Laboratory, showed how aging impedes the brain's ability to clear away toxic protein aggregates.

The Salk Institute, overlooking the ocean in La Jolla, supports 56 faculty members and a scientific staff of more than 850 conducting biological research. Photo courtesy of Salk Institute

Dillin and his team employed the help of tiny Methuselah worms that, despite their advanced age, still have a youthful spring in their crawl. These creatures proved that slowing the aging process also reduced the formation of toxic beta amyloid aggregates. The finding opens the door for development of drugs preventing build-up of toxic protein aggregates in the brain.

While aging is the greatest risk factor for Alzheimer's disease, another study this year by Paul Sawchenko, a professor in the Neuronal Structure and Function Laboratory, suggests that low levels of stress, the kind we experience each day, can also contribute to the onset of Alzheimer's disease.

The findings showed how the brain-damaging effects of negative emotions lead to a molecular chain reaction that cause modification of the tau protein, which collapses into insoluble fibers inside neurons. This ultimately leads to cell death. Currently, drugs in Stage 2 clinical trials for the treatment of depression and other mood disorders target the same receptors involved in Sawchenko's study.

"We may have discovered another application," Sawchenko said. "Such drugs could have a prophylactic effect or delay the progression of Alzheimer's disease."

Juan Carlos Izpisúa Belmonte, a professor in the Gene Expression Laboratory, garnered international attention most recently when he and his team published a study explaining how they regenerated the wing of a chick embryo -- a species not known for its ability to regrow limbs.

By manipulating a specific cell-signaling pathway, Belmonte was able to deactivate the system in animals with the ability to regrow limbs (salamanders, frogs and zebra fish), while activating it in chick embryos, which regenerated a perfectly functioning wing after removing the original appendage. The study suggests that the potential for such regeneration exists innately in all vertebrates, including humans.

While manipulating the same system in humans is not possible at this point, Belmonte hopes these findings may eventually offer insights into current research examining the ability of stem cells to build new human body tissues and parts.

The Salk Institute's stem cell program has continued to strengthen with the help of philanthropic contributions and more than $7.4 million in grants provided by the California Institute for Regenerative Medicine. Construction is already underway at Salk on a new stem cell core facility that will serve as a training center for the next generation of scientists who work in this very promising field of research.

Further securing Salk's commitment to this emerging field is the institute's participation in the San Diego Consortium for Regenerative Medicine. Salk's contribution to this historic partnership is its team of established stem cell experts as well as scientists whose work in gene expression and related fields is central to understanding how stem cells can be developed for therapeutic purposes.

Looking ahead, the institute is also interested in the burgeoning field of live cell imaging and biophotonics, which uses single quantum units of light to "see" molecules. Applying such advanced technology overcomes the resolution limit of light microscopy and enables scientists to understand how single molecules and cells function in real time and decipher what goes wrong when they malfunction.

Knowledge gained from this advanced technology will help resolve still-unanswered questions surrounding many human conditions. It will also enable Salk scientists to ask new questions about biological systems, transform the way they analyze complex systems such as the brain and revolutionize the way diseases are treated.

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