Indiana University

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Thursday, February 8, 2007

Last modified: Thursday, February 8, 2007

Math models add more options for life sciences, cancer researchers

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Feb. 8, 2007

BLOOMINGTON, Ind. -- Imagine being able to take a fantastic voyage into the human body and see how life evolves in a single cell, observe what triggers and sustains a beating heart -- or perhaps journey into a tumor to witness how cancer destroys life.

Such a possibility is not the stuff of overactive imaginations or sci-fi films; it's the domain of Assistant Professor Santiago Schnell, who heads the Systems Biology Laboratory at the Indiana University School of Informatics. Systems biology offers a multidisciplinary approach to studying biological phenomena by integrating research techniques and methodologies from biology, chemistry, physics, engineering, mathematics and computer science.

This collaborative endeavor uses mathematical modeling to better understand the origin and progression of life systems. And that approach is explained in large part in "Multiscale Modeling in Biology," featured in the March-April issue of American Scientist. Schnell, the principal author, is joined by Ramon Grima, of London's Imperial College; and Philip K. Mani, of the University of Oxford.

"Firmly rooted in observation and experiment, biology for decades had little use for mathematical modeling, which was, in any event, a slow business until computers made it possible to simulate large complex systems of nonlinear equations," said Schnell, assistant professor of informatics, who holds adjunct appoints in physics and biology.

"Today," Schnell added, "biologists and mathematicians desperately need one another -- not just to find structure in the vast quantities of data flowing from experiment but also to integrate this information into models that explain at multiple scales of time and of space how life works."

Schnell and his colleagues have numerous ongoing research projects using multiscale modeling. One endeavor, funded by the National Institutes of Health, studies how early embryo-made segments form blocks of cells that are precursors of the vertebrate. Failures in segmentation can be fatal or can cause developmental abnormalities such as scoliosis and spina bifida.

Schnell also has been working on a modeling project based on genetic and molecular features of the evolution of colorectal cancer and the effectiveness of treatments. The study appeared in Theoretical Biology & Medical Modelling a year ago and has garnered much attention from cancer researchers and scientists. This work is ranked first among the most viewed articles of all time in the journal.

"We now have a good deal of information about the genetic mutations underlying colon cancer and how activation of the mutated genes is affected by oxygen starvation and overcrowding," Schnell said. "We can model the life cycle of a cell in its various stages and how it is influenced by environmental changes."

More specifically, they are constructing a model to predict what proportion of cells would be sensitive to radiation therapy at different stages of tumor evolution. Currently, radiation is administered to cancer patients using extensions of a 20-year-old model that assumes tumor sensitivity and population growth are constant during radiotherapy.

"We found that radiation doses administered to stressed cells are effective, but radiation administered after the tumor reaches an oxygen-starved condition has little effect because most of the cells have become inactive," said Schnell.

Mathematical modeling of biological systems, including cancer, poses challenges on several fronts, Schnell said. The first is to ensure the collection of qualitative and quantitative experimental observations, and that requires closer collaborations with scientists from several disciplines. A second task is to construct a model that has a reasonable amount of precise parameters to simplify a problem without losing its essentials.

"The use of mathematical ideas, models and techniques is rapidly growing and increasingly important throughout life sciences," Schnell observed. "The development of new programs has eliminated the well-demarcated divisions between theory and experiment. The culture of biology is changing with a growing awareness that, as a colleague recently told me, 'to think is to model.' "

More information about the Systems Biology Laboratory at the IU School of Informatics is at To arrange an interview with Santiago Schnell or to receive a copy of the American Scientist article, contact Joe Stuteville at 317-946-9930 or

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