By Gail Gallessich

Traveling across time zones upsets our biological clock, or circadian rhythm, but soon the body adjusts to the new day/night cycle. New studies of the computational models of the circadian rhythm of fruit flies show that the internal clock is robust and not easily perturbed. These studies may eventually lead to greater understanding of jet lag as well as diseases in humans.

Engineers at UCSB’s new Institute for Collaborative Biotechnologies, and Germany’s Max Planck Institute (MPI) for Dynamics of Complex Technical Systems, have analyzed the mechanism of genetic circuits by which the fruit fly regulates its circadian rhythm. The results were published in the Proceedings of the National Academies of Science.

The mechanism controlling the biological clock generates a complicated dynamic behavior, oscillating back and forth and making it difficult to study, but also making it a prototypical, dynamic cellular system.

The circadian rhythm of the fruit fly takes its cues from the sun. When the sun rises it affects the light-sensitive neurons in the brain of the fruit fly. Reactions of proteins are triggered at a certain rate depending on the amount of light. The reactions set the clock.

There are key proteins and two key feedback loops involved, making the system a hierarchical control scheme, a design often used in engineering.

The engineers were looking for the principles underlying the architecture of the fruit fly’s system that enables it to be so robust, according to co-author Frank Doyle, a chemical engineering professor who holds the Mellichamp Endowed Chair in Process Control. “We are very excited about this collaborative work, and how systems engineering ideas and tools can be used to unravel design principles in a complex biological system,” he said.

The authors analyzed the circuitry of the fruit fly because it is one of the most studied of all organisms. They were able to take mathematical information from the scientific literature on fruit flies and perform computations to derive their findings.

They made systematic changes to the mathematical model to find the points of greatest fragility. They discovered that the trade-off between robustness and fragility is largely determined by the architecture of the regulatory system, and that keeping accurate time may increase the fragility of the global machinery.

In Germany, co-author and lead MPI researcher Joerg Stelling commented, “Implications of the systems approaches in this collaborative work are to shed light on the function of individual control circuits in biology, with a long-term perspective to rationally understand causes of diseases.”