Systems Biology
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. During the last 3 years our 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. These studies identify the sources of coherence in the annual spawning of certain species of coral, and this builds on the group’s expertise in robustness analysis of coupled oscillators in the brain that are responsible for circadian rhythms. Our medical systems biology studies have expanded to include Diabetes, Alzheimers Disease, Heat Stroke, and PTSD.

Biomedical Control
A main focus of research in our group for the past two decades has been the development of automated control of insulin delivery to regulate blood glucose in people with type 1 diabetes. The progress we have made in this area has resulted in a functional artificial pancreas that has been evaluated successfully in several 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 gained regulatory approval to conduct the first fully outpatient evaluation of our control algorithm. This study will take place during the following year at sites including Stanford University, Mayo Clinic, and University of Virginia. In addition our software system, the portable Artificial Pancreas System (pAPS), has been used by 10 clinical sites around the globe.

Our technical contributions to artificial pancreas research include: a zone model predictive control strategy, a method for hypoglycemia alarming, a personalized 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 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 work has matured from theoretical developments (last 15 years) to clinical testing (last 5-7years) to commercial interest in licensing (currently). 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.

To learn more about the specifics of our research, please choose an area of interest above.