The Jackson Laboratory in Bar Harbor has been awarded more than $15 million in federal grant funding to advance the science of “systems genetics” – studying the mouse genome in a way that will help scientists understand the interplay between genetics and the environment.

Researcher Gary Churchill said Thursday the grant will be used to study conditions that arise out of the relationship between an individual’s genetic makeup and external factors such as diet, exercise and exposure to environmental toxins.

There are literally hundreds of disorders that are known to be linked to a single genetic defect – conditions such as cystic fibrosis and Huntington’s disease, Churchill said. While potentially devastating to affected individuals and their families, he said, most of these diseases are quite rare. With the field of genetic research accelerating, these “single-gene” conditions are increasingly likely to be identified and linked with the specific gene mutation that causes them.

But the “big diseases” that affect large segments of the population and place a huge burden on the health care system are more difficult to understand, he said. “Heart disease, cancer, diabetes, obesity – we really haven’t made much headway in understanding them, because they’re so complex,” he said. Unlike the single-gene conditions, scientists don’t think these more common diseases are linked to a single mutated or “broken” gene. Rather, he said, they are likely to result from incompatibility between gene clusters and environmental factors – a “systems” problem.

Churchill likened the systems approach to genetic research to understanding a car engine, crediting his Bar Harbor mechanic with the analogy. “You can’t hook a Ferrari engine up to a Volkswagen drive train and expect good performance,” he said. “The individual parts may be perfectly good, but they don’t work well together.”

What that means in mammalian genetics terms is that combinations that may have worked well for our long-ago ancestors may spell disaster for present-day humans. For example, Churchill said, “Our hunter-gatherer forebears would bash a woolly mammoth over the head and eat woolly mammoth every day for a week; then maybe they wouldn’t eat much of anything for a while.”

In that situation, he said, a gene that promotes the storage of food energy in the form of body fat would be an advantage, maybe even essential for survival. But now, when woolly mammoth is on the menu virtually every night, the high-fat diet of many Americans coupled with the evolutionary predisposition to limit insulin production may lead to diabetes. “The parts themselves aren’t defective, but they come together in ways that don’t work,” Churchill said.

Scientists at the Jackson Laboratory use mice in their research because the mouse genome is nearly identical to the human genome, making it likely that lab findings eventually will be applicable to human health. Mouse strains can be developed to reflect specific genetic traits that make them roughly analogous to different human populations, and their environments are carefully controlled for diet and other factors.

The five-year grant, awarded by from the National Institute of General Medical Sciences, part of the National Institutes of Health, mandates recipients to “seek out and broaden the base of researchers,” Churchill said. Designing experiments that manipulate a multitude of environmental and genetic variables, and computing the multifaceted results, requires the skills of many disciplines. Churchill said the new systems project will tap the abilities of mathematicians, physicists, molecular biologists and others not normally associated with genetic research. His own background is in mathematics and statistics, he noted.

“Math isn’t just for accounting; it’s for understanding and using data,” he said.

The Jackson Lab joins six other systems biology centers that have been funded by the NIH grant. The others are Harvard University, Princeton University, Case Western Reserve University in Cleveland, the Massachusetts Institute of Technology, the University of Washington, and the Seattle-based Institute of Systems Biology.