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12/22/2008 08:00:00

Three Caltech Scientists Receive Ellison Medical Foundation Awards

The Senior Scholar Awards are aimed at promoting basic research into the underlying processes that control aging

PASADENA, Calif.--The Ellison Medical Foundation (EMF) has awarded Senior Scholar Awards of nearly $1 million each to three California Institute of Technology (Caltech) researchers for exploratory projects in the molecular biology of aging processes and age-related diseases.

The brainchild of Laurence J. Ellison, Oracle cofounder and CEO, and Nobel Prize-winning biologist Joshua Lederberg, the EMF supports basic research that integrates molecular biology and the biomedicine of aging. Its Senior Scholar Awards fund exploratory work by acclaimed researchers, many new to the study of aging. Over the past decade, a board of six distinguished scientists has selected awardees by adhering to Lederberg and Ellison's belief that the way to get positive scientific results was to "look for smart people who had track records of creative, productive work and who had a good idea," according to EMF's website. The foundation would then "give them money and stand back. It would favor basic research that was too risky or speculative to attract mainstream funding."

Caltech's awardees take that mandate seriously. For instance, Jacqueline Barton, the Arthur and Marian Hanisch Memorial Professor and professor of chemistry, plans to use her Senior Scholar Award to explore novel ways the body can defend itself against oxidative damage, a major contributor to aging. Barton is known for her work in understanding charge transport in DNA--examining the way in which electrical charges are moved along a DNA strand, and what role charge transport plays in creating DNA damage. But now she is beginning to consider ways in which charge transport might actually be protecting DNA as well. For instance, Barton believes that DNA charge transport may provide a way for the DNA to send out a long-range signal when it undergoes oxidative damage, alerting DNA-bound proteins such as p53--known as "the guardian of the genome" because of its role in cancer prevention via DNA repair--to set into motion the processes that will eventually lead to the mending of damaged strands. "This would be a paradigm shift with respect to current biological mechanisms for cellular activation," says Barton.

Judith Campbell, professor of chemistry and biology at Caltech, is exploring the ways in which a yeast protein her lab discovered--a DNA-synthesizing enzyme called Dna2--might work to safeguard the bits of DNA at the end of chromosomes, called telomeres. Telomeres are made of repeated sequences of DNA and act to protect the ends of the chromosome from damage, much like the plastic wrapped around the end of a shoelace. Each time a cell divides, however, its telomeres get a little bit shorter; eventually, this aging process leads to the cell's death. But what Campbell has found is that, in yeast at least, Dna2 seems to help maintain the length of the telomeres, slowing down the aging process. She intends to use her Senior Scholar Award to begin studying Dna2 in humans, rather than yeast. "Extending our work to human cells will allow me to contribute to the application of fundamental biology to the improvement of human health," she says. "This has been a burgeoning but frustratingly slow field. We hope this award will allow us to identify new targets--including but not limited to Dna2--whose manipulation can lead to telomere stability. This can, in turn, be expected to have an effect on the life span of the organism as a whole, by keeping at least some of the diseases of aging at bay."

David Baltimore, Caltech President Emeritus and Robert Andrews Millikan Professor of Biology, has been researching the role of tiny bits of RNA--called micro-RNAs or miRs--in the process of aging. First discovered in the 1990s, micro-RNAs appear to control gene expression and seem to play a role in the development and inhibition of cancer, in the development of immune cells, and in the body's response to inflammation. According to Baltimore, miRs can influence a wide variety of behaviors in cells--everything from differentiation to proliferation to functional behavior. Baltimore's group will use the Senior Scholar Award to compare the micro-RNA profiles in the cells of young mice to the profiles found in the cells of old mice. They will focus particular attention on specific miRs they have already discovered, which they have found to play a role in inflammation--a process that seems to increase as we age. "When we find an miR that is affected by aging, we will examine its targets, its cellular specificity, the effects from its overproduction, and the consequences of a knockout," says Baltimore.

"This award spotlights three of Caltech's most prominent researchers in the field," says Caltech president Jean-Lou Chameau. "It recognizes not only the promise of their research efforts, but also the originality of the ideas which they are pursuing. It is from these sorts of programs--programs that are aimed at allowing researchers to venture into new research arenas--that real creativity is nurtured."

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About Caltech: Caltech is recognized for its highly select student body of 900 undergraduates and 1,200 graduate students, and for its outstanding faculty. Since 1923, Caltech faculty and alumni have garnered 32 Nobel Prizes and five Crafoord Prizes.

In addition to its prestigious on-campus research programs, Caltech operates the W. M. Keck Observatory in Mauna Kea, the Palomar Observatory, the Laser Interferometer Gravitational-Wave Observatory (LIGO) and the Jet Propulsion Laboratory. Caltech is a private university in Pasadena, California. For more information, visit http://www.caltech.edu.

Written by Jon Weiner