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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.
Over the past 15 years our group has pioneered the application of model predictive control for regulation of insulin delivery to regulate glucose. These developments are converging rapidly on a prototype artificial pancreas. As reported in previous reviews, we have a rich collaboration with the Sansum Diabetes Research Institute for our clinical investigations. During the last 3 years, we have worked to achieve regulatory oversight on our clinical trials (which are now approved), and have expanded the clinical sites for testing to include Tel Aviv, Montpelier, Padova, and Charlottesville. Our software system, entitled the Artificial Pancreas System (APS) is now being licensed at approximately 10 sites around the globe for clinical trials. Our technical developments include: a method for hypoglycemia alarming, a zone model predictive control strategy, a safety mechanism to limit insulin overdosing (insulin on board), monitoring and telemedicine (E911) and schemes for improved day-to-day management of insulin dosing (iterative learning control). Our work has matured from theoretical developments (last 10 years) to clinical testing (last 3-5 years) to commercial interest in licensing (currently). We have relationships with several of the leading companies working in the insulin pump and glucose sensor fields.
To learn more about the specifics of our research, please choose an area of interest above.
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