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UCSF Researchers Identify Two Key Pathways in Adaptive Response
Date:8/21/2009

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"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 used a computational method to analyze 160 million circuits that come into play when a cell adapts to environmental stimuli and monitored them for the circuit's sensitivity to a stimulus and the precision of its adaptation.

The result was an exhaustive circuit-function map of enzymatic regulatory networks that identified two core structures that are common to every adaptive response, however simple or complex: a negative feedback loop with a buffering node, and a feed-forward loop that adjusts the proportion of response. Furthermore, the researchers said, they established that the most robust adaptive responses rely heavily on at least one of these two minimal motifs.

"This is a new way of looking at biology and disease," Lim said. "We've sequenced the genome, we know the genes involved and have started to understand how they're connected together. But it's like opening your computer and looking at the chips and circuits inside - how do you begin to understand it?"

Unlike chemistry, in which the core elements were understood 100 years ago, there is no equivalent of the periodic table in the field of biology. The field of systems biology, in which both Lim and Tang focus, aims to create that same systematic approach to understanding how cells and biological systems work.

The goal is to break down the overwhelming amount of information that has been generated by advances over the last decade in genetic sequencing, into recognizable modules that can then be further studied
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