A major research award will help a University of Wisconsin-Madison scientist uncover the rules that govern the complicated metabolic interactions common to all living cells.

Diana Downs received the five-year, $450,000 award in an international competition. The James S. McDonnell Foundation made the award to Downs in November as part of its 21st Century Science Initiative for Complex Systems Analysis.

Downs, a microbial physiologist in the Department of Bacteriology at the College of Agricultural and Life Sciences, wants to understand how cells integrate their network of metabolic pathways. In the process, she hopes to design approaches to complexity that will be applicable to other systems.

“Nature is full of diverse processes that function with an efficiency unmatched by systems people have designed,” Downs says. “Hidden in biological systems are the solutions to problems that technology will be asked to solve in the future. If we understood the complexity of a living cell, we would be in a better position to harness biological systems for the economic, environmental and medicinal benefit of society.”

Downs is trying to understand how a cell”s core metabolic pathways — there are more than 100 that run constantly — interact with each other to maintain a healthy cell. Effective coordination of these metabolic processes is essential for the function of each cell. In the past, largely due to technical limitations, researchers focused primarily on understanding one metabolic pathway at a time.

“Our strategy has been to utilize genetic techniques to identify metabolic connections to one central pathway and thus build a defined network which we can then dissect on the molecular level,” says Downs.

“These pathways are like a spider”s web,” she says, “and a change in one can affect many others. Advances in DNA sequencing and genomic analyses have opened doors for us. Now we can begin to examine how the compounds produced in one pathway change what”s happening in other pathways. Addressing questions of this complexity has not been technically feasible until the last seven to ten years.”

Downs studies the complexity of a living cell by using a bacterial cell as a model. She has focused on the pathway for producing thiamine, more commonly known as vitamin B1. Her research confirms that central metabolism is extensively integrated, and that this integration can now be studied. She has demonstrated that a variety of metabolic pathways, and previously undescribed functions, affect the cell”s ability to make thiamine.

The McDonnell Foundation was established in 1950 by the late James S. McDonnell, Jr., founder of McDonnell Aircraft Corporation, to support scientific, educational and charitable causes. Its primary interests are in the biomedical and behavioral sciences.