The funding will come from the National Institute of Neurological Disorders and Stroke, a component of the National Institutes of Health (NIH). According to Kennedy, who is the Allen and Lenabelle Davis Professor of Biology at Caltech, the five-year project is innovative because it will integrate advanced computational methods with experiments to better analyze and model calcium signaling in the brain. In addition to Kennedy's research group at Caltech, the program will involve research teams from the Salk Institute, Cold Spring Harbor Laboratory, and the University of North Carolina.
"Another aspect of this research that is quite new is the application of these kinds of methods at the molecular level," she says. "This is important because, for about 20 years or so, it wasn't really possible to be rigorously quantitative about the biochemical functions of synapses at the molecular level. This was because we didn't know all the molecules that were involved."
With new advances, especially the completion of the Human Genome Project, it is now time for a new phase in research on the molecular mechanisms of brain functions, according to Kennedy. In addition to basic improvements in knowledge of how brain signaling works, the research program could also lead indirectly to pharmaceutical advances.
"Neurological and mental diseases result, in part, from derangements in regulation of synaptic transmission," Kennedy says. "In a type of neuronal structure known as dendritic spines -- so named because they sort of look like spines -- calcium influx through a certain type of receptor is a principal regulator of synaptic strength, or plasticity. Thus, calcium can lead to increases or decreases, of varying durations, in synaptic strength."
The program includes four projects and a core that will provide new computer software. One project will use a computer program called MCell to develop and test models of calcium dynamics in spines. Another will rely on microscopy to study the organization of calcium sources and sinks in spines, as well as calcium distribution. A third, which will be centered in Kennedy's lab, will develop and test kinetic models of enzymes regulated by calcium; and a fourth will use advanced imaging techniques to measure calcium signals and their regulation in individual spines.
The program will be highly interdisciplinary, Kennedy says. Three physicists will be among the team members in her lab. Work at the other institutions, as well, will involve specialists from disciplines outside biology.
"Once we have a better quantitative understanding of signaling, it will be possible to ask much 'cleaner' questions about what kind of drugs will treat certain conditions, and under what circumstances."
Contact: Robert Tindol (626) 395-3631