Professor of Engineering and Applied Sciences

The Doyle group is a leading force on the computational side of the field of systems biology. Our ongoing work on circadian rhythms continues to probe at the sources of regulation that give rise to highly precise periods in the mammalian ‘biological clock’. We have also begun to make preliminary links between clock performance and cognitive function. One of the most profound contributions from our group is the development of a cell autonomous mathematical model of the circadian oscillator, which resolves the experimentally observed discrepancies between the tissue (and animal) scale and the cellular scale. Our ongoing work involves elucidating the mechanisms and networks driving coherence in populations of cellular circadian oscillators. Research efforts in systems biology have expanded into the application domains of ecology, with the broad technical theme of understanding synchronized population-scale phenomena, such as coral spawning, using coupled and driven oscillator models. Our medical systems biology studies have expanded to include Diabetes, Alzheimers Disease, Heat Stroke, and PTSD.

Over the past two decades, our group has been working toward the development of automated control of insulin delivery to regulate glucose in people with type 1 diabetes. This has resulted in a functional artificial pancreas that has been evaluated successfully in numerous clinical studies. Our work has been greatly enriched by our collaborations with the William Sansum Diabetes Research Center in Santa Barbara, CA, along with other clinical research facilities around the world. In the past year, we have worked to achieve regulatory approval to conduct the first fully outpatient evaluation of our control algorithm. Our software system, the portable Artificial Pancreas System (pAPS), has been used by 10 clinical-sites around the globe for clinical trials. Our technical contributions to artificial pancreas research include: a method for hypoglycemia alarming, a zone model predictive control strategy, a personal model predictive control algorithm, a safety mechanism to limit insulin overdosing (insulin on board), monitoring and telemedicine, and schemes for improved day-to-day management of insulin dosing (iterative learning control). We have also conducted pilot studies of innovative new approaches such as the use of intraperitoneal insulin delivery for the artificial pancreas and the use of inhaled insulin to supplement closed-loop glucose control. Our collaborative relationships with leading diabetes technology companies have allowed us to move quickly from bench to bedside to evaluate our ideas in real-life scenarios.  

T. Hirota, J. Lee, P. St. John, M. Sawa, K. Iwaisako, T. Noguchi, P. Pongsawakul, T. Sonntag, D. Welsh, D. Brenner, F.J. Doyle III, P. Schultz, and S. Kay, “Identification of Small Molecule Activators of Cryptochrome”, Science, 337, 1094-1097, 2012.

E. Dassau, H. Zisser, R. Harvey, M. Percival, B. Grosman, W. Bevier, D.E. Seborg, L. Jovanovic, and F.J. Doyle III, “Clinical Evaluation of a Personalized Artificial Pancreas”, Diabetes Care, 36, 801-809, 2013.

F.J. Doyle III, L.M. Huyett, J.B. Lee, H.C. Zisser, and E. Dassau, “Closed-Loop Artificial Pancreas Systems: Engineering the Algorithms”, Diabetes Care, 37, 1191-1197, 2014.

P.C. St. John, T. Hirota, S.A. Kay, and F.J. Doyle III, “Spatiotemporal separation of PER and CRY post-translational regulation in the mammailian circadian clock”, Proc. Natl. Acad. Sci. USA, 111, 2040-2045, 2014.

G.S. Thakur, B.J. Daigle, Jr., K.R. Dean, Y. Zhang, M. Rodriguez-Fernandez, R. Hammamieh, R. Yang, M. Jett, J. Palma, L.R. Petzold, and F.J. Doyle III, “Systems Biology Aproach to Understanding Post-traumatic Stress Disorder”, Molecular BioSystems, 11, 980-993, 2015.