Dan Cook

Brief Biography

Professor Cook has leveraged his training in mechanical engineering to make significant contributions to our understanding of insulin secretion and diabetes and, more recently, to the formal representation and analysis of biological systems. While training and working as a mechanical engineer, Dr. Cook modeled the dynamics of glucose-induced insulin release prior to entering MD-PhD program at the University of Washington (UW). Beginning with his graduate laboratory studies, he demonstrated two critical features of glucose-induced insulin secretion: (1) that the rhythm of beta cell membrane electrical activity (mediator of beta-cell calcium uptake and insulin release) depends on membrane depolarization, and (2) that glucose-induced depolarization is mediated by ATP-sensitive potassium channels (KATP). Dr. Cook collaborated with others to incorporate these observations into quantitative models that are the basis for current mathematical research into insulin secretion and diabetes.

Facing a lack of biology-oriented computational tools for representing and analyzing physiological systems in the late 1990’s, Dr. Cook developed Chalkboard, an application for graphically representing biological systems and computing qualitative responses to perturbations of chemical concentrations and reaction rates. To generalize on this approach, Dr. Cook began a long and fruitful collaboration with the UW ontologists who pioneered the Foundational Model of Anatomy (FMA) ontology to develop the Ontology of Physics for Biology (OBP; http://bioportal.bioontology.org/ontologies/OPB). OPB is a formal ontology of physical concepts and entities that are the basis for analyzing multiscale (chemical to organismal) and multidomain (biochemistry, fluid mechanics, diffusion, etc.) physiological systems. Based on the OPB and other ontologies, the Semantics of Biological Processes group (SBP; http://sbp.bhi.washington.edu) has developed and deployed powerful computational tools for representing, decomposing/recomposing, and reusing the biological content of the 100’s of biomathematical models available in several modeling resources.

Multiscale/multidomain biological processes – a semantic basis for modeling and analysis

Descriptions of biological processes are pervasive in our understanding how biological systems function in health and disease. We speak, for example, of how the secretion of insulin is required for the uptake of glucose by muscle cells, and how glucose is metabolized to fuel muscle contractions, and how disrupted insulin secretion causes diabetes. This parsing of organismic function into entities—the parts of organisms—and the processes by which they interact is fundamental to how we observe, analyze, and ultimately control biological function. Given the broad range and great importance of physiological processes to biomedicine, a major ongoing challenge is creating computable representations for archiving, searching, and accessing physiological knowledge frommolecular to organismal processes. As a bridge between the bioinformatics of “systems biology and efforts to develop quantitative computer models of multiscale physiology, we have established a formal semantics of classical biophysics and a set of software tools that leverage those semantics to represent and analyze complex systems at multiple scale (molecules to organisms) and across multiple domains (e.g., chemical kinetics muscle contraction, blood flow, etc.). Our semantic model representations translate readily between qualitative and quantitative analytical domains.