Daniel Beard at the Medical College of Wisconsin (Milwaukee) is leading the virtual rat project.
Due to their similar physiology, lab rats have already helped find cures for cardiovascular diseases in humans. But housing, feeding and breeding them is costly. Now the National Institutes of Health is aiming to simplify procedures by creating virtual rats that behave just like the real thing. The five-year $13 million NIH-funded effort aims to develop models of interventions that can be perfected in rats. The models will then be used to mitigate human disease--from high blood pressure to heart failure.
Unlike the European Union's Virtual Physiological Human project, which aims to perfect models of human biological functions, the Virtual Physiological Rat project instead aims to determine why genetic dispositions express themselves as disease, and how to prevent it.
Researcher Daniel Beard of the Medical College of the University of Wisconsin (Milwaukee)
"The goal of the rat project is to determine why an individual rat comes to have certain markers of cardiovascular disease, to predict what markers which rats will develop and why, and to engineer new rats to test out predictive understanding," said computational biologist Daniel Beard at the Medical College of Wisconsin (Milwaukee).
Beard, who will be running the Virtual Physiological Rat program, said computer models of rat physiology have already been used to advance the state of understanding of cardiovascular disease, which is the leading cause of death in people worldwide.
The new Virtual Physiological Rat simulation will extend that understanding to the environment, thus enabling researchers to unearth the complex inter-relationships between multiple genes and their real-world expression.
Live-rat experiments will still be used, but only for advanced diagnostics aimed at verifying the accuracy of rat simulations. As the model grows in complexity, the researchers will be able to do what-if simulations about the effect of interventions. They will then use experiments to verify or falsify their hypotheses.
The project will begin by bringing together all the knowledge accumulated about rats with known genomes, such as how properly functioning hearts, kidneys, skeletal muscles and blood vessels work together to produce healthy rats. Once a detailed model of a healthy rat's cardiovascular system is completed, the researchers will use the model to make predictions. They will then go into the lab to verify that live rats respond in the manner predicted by the model.
Once a healthy rat's physiology has been successfully tested, Beard's group plans to extend the model to rats with high-blood pressure and other cardiovascular diseases, hopefully to find a relationship between these conditions and specific genes and the environmental factors that contribute to their expression. Eventually, Beard hopes to create detailed rat analytics that can recommend early interventions to stop heart disease from developing. To test the prowess of the final rat analytical model, Beard plans to breed new strains of rats with novel new genetics.
"We are using a number of defined genetic strains that have interesting cardiovascular phenotypes that mimic important aspects of human disease. We also plan to engineer new strains as useful throughout the life of the project," said Beard.
By predicting the cardiovascular health of new strains, and making recommendations on early interventions, the researcher can follow up with live rat experiments to confirm or falsify those hypotheses, thus enabling predictive analytics to be developed and perfected. Beard's team will also include scientists from the United Kingdom, Norway and New Zealand.
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