Overview

Why does a child look like her parents?

At the start of the last century, this simple question defined one of nature’s great mysteries. We knew, of course, how her parents made the fertilized egg. But it was a mystery how their traits were encoded in the physical stuff of the egg, or how these traits were expressed as she developed. Many pioneering discoveries later, we know those heritable traits are encoded as genes in DNA.

A key advance in our understanding was linking genes to traits. More than 50 years ago, Linus Pauling showed how a single mutation in the gene for hemoglobin, a protein in blood cells, made the cells adopt a sickle-like shape. The shape hampered the cells’ ability to circulate and function, defining traits for the disease sickle cell anemia. More broadly, Pauling’s discovery led scientists to think about disease traits in terms of underlying genetic and molecular mechanisms.

Advances during the last 25 years have found that ailments such as cancer, heart disease and diabetes arise as the result of mutations in multiple (rather than single) genes. Further, the behavior of genes — normal or mutant — can be influenced by environmental factors as seemingly benign as ambient temperature, food intake and physical activity. By better understanding how genes interact with each other and with our environment, we are approaching a deeper understanding of human health and disease.

But the reality of life is still more complex. During the last decade, new discoveries have revealed that no one lives in isolation. Every human is a complex ecosystem, in continuous exposure to a diversity of microbial cells and viruses present on our skin, in our guts and in our tissues.

“No organism is an island,” says John Yin, professor of chemical and biological engineering at the University of Wisconsin-Madison. “We have known for a long time how bacteria and viruses can cause human disease, but the new data suggest they also have important and intriguing roles in promoting our health.”

With a wealth of new information, we can pose increasingly precise questions about how nature and nurture affect life. Such insights are needed for understanding how microbes and viruses could harm or help human health. In essence, these are the challenges taken on by systems biology research at the Wisconsin Institute for Discovery.

As complex as we are, the human being can be an overwhelming research model. Viruses, on the other hand, carry small and well-understood genomes, have short reproduction times and stand as the cause of a number of human diseases.

“The study of single organisms, such as microbes, worms and humans, will continue to enhance our knowledge,” Yin says. “But today, the broadest frontiers are to understand how interactions between different organisms impact whether they persist or decay.”

With Yin as leader, the goal of systems biology research at the Wisconsin Institute for Discovery is to gain insights into how different organisms cooperate or compete — a problem that will be tackled using approaches and perspectives drawn from diverse fields, including ecology and evolution, physics and chemistry, engineering, mathematics and computer science.

Our ultimate aim is to advance models that can predict the likelihood that a microbe can survive and flourish given its environmental surroundings, and to promote human health through effective management of microbe-host interactions.