UCSF researchers have identified the two key circuits that control a cell's ability to adapt to changes in its environment, a finding that could have applications ranging from diabetes and autoimmune research to targeted drug development for complex diseases.
The new findings are featured as the cover story in the August 21, 2009 issue of the journal "Cell" and are available online at http://www.cell.com.
The limited number of circuits that can achieve adaptation represents a fundamental shift in our understanding of this important biological behavior, which previously had been thought to be affected by hundreds of different circuits, according to Chao Tang, PhD, who was co-senior author on the paper with Wendell Lim, PhD.
Both Lim and Tang are faculty members in the UCSF departments of Bioengineering and Therapeutic Sciences and of Biochemistry and Biophysics, and are affiliated with the California Institute for Quantitative Biosciences (QB3) at UCSF.
Adaptation is a fundamental property of many cellular sensing systems, allowing the cell to automatically reset itself after responding to a stimulus, Lim said. These adaptive circuits are what enable eyes to adjust to changes in light, white blood cells to move toward bacteria, or insulin levels to adjust to sugar loads. They are involved in heat adaptation, movement, sight and smell, among others. They also are often the mechanisms that go wrong at a molecular level in some of the most difficult diseases to treat.
"Many diseases are diseases of homeostasis," explained Lim, who is also affiliated with the Howard Hughes Medical Institute. "Diabetes or autoimmune diseases, for example, are based on a disruption in the circuitry that prevents the body from readjusting itself."
Until now, however, the millions of circuits involved in that adaptive response were impenetrably complex.
For this research, the team us
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University of California - San Francisco