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Cornell University, Gene Network Sciences (GNS) and the University of California, San Diego (UCSD) have been selected by the National Heart, Lung, and Blood Institute of the National Institutes of Health to receive a $2 million, four-year Bioengineering Research Grant. The funds will be used to develop a data-driven computer model of the canine ventricle that will serve as a useful representation for other species, including humans. "This partnership between scientists at Cornell University, UCSD and GNS is a model of academic/private sector cooperation. Each partner will contribute unique and essential expertise to this project which may lead to new methods for treating lethal heart rhythms and save lives," said Kraig Adler, vice provost for life sciences at Cornell. The research team will take a staged approach, tapping into the specific proficiencies of each group. Ionic currents of single heart cells obtained from different parts of the ventricles will initially be characterized experimentally in Dr. Robert Gilmour's lab at Cornell. The resulting data will be used by GNS, led by Dr. Jeffrey Fox, to construct computer models of different types of heart cells. These will be incorporated into an anatomically realistic, 3-D computer model of a canine ventricle. The model will then be used to test candidate mechanisms for the development of ventricular fibrillation, aided by Dr. Wouter-Jan Rappel of UCSD, who will refine techniques to handle the project's high computational demands. Rappel will also be contributing models of intracellular calcium dynamics. "Cardiac disease/arrest has long been the leading cause of death in the United States, and therapy for ventricular fibrillation (VF) has been largely ineffective," said Dr. Gilmour, professor of physiology and associate dean for research and graduate education at Cornell's College of Veterinary Medicine. "Our goal in creating the 3-D computer model is to better understand the underlying mechanisms for VF and to eventually have a significant impact on the diagnosis and treatment of deadly heart rhythm disorders." Gilmour and Fox have collaborated for four years, publishing multiple papers on heart dynamics. Their work has included the development of a canine ventricular cell model that will serve as a basis for this expanded effort. Gilmour brings more than 25 years of experience in cardiac electrophysiology to the team. Fox was one of the first employees at GNS, an Ithaca-based company that has created the largest predictive dynamical model of a human cancer cell. "GNS research in large-scale dynamical cell simulations will be extremely helpful in creating the heart model. In addition, development of the 3-D model will extend the capabilities of the GNS technology platform to simulate biological processes across multiple scales from molecular interactions to cell and organ level behavior," said Dr. Fox, director of physiology at GNS. "A computer model that can simulate catastrophic heart disturbances like VF will allow us to observe what happens during these events in ways that are impossible in the lab. The challenge will be to develop a sufficiently comprehensive model; that is, one that captures the relevant biological details that determine cardiac electrical activity," continued Fox. "Such a project can only succeed if there is an iterative process in which the in silico model and in vitro experiments constantly inform one another. Our close relationship and proximity to Robert's lab at Cornell will enable that to happen."