Bringing Computers Into Biology

Image: Adapted with permission from AJP - Cell Physiol

The explosion of data from gene sequencing projects has left biologists scrambling to make sense of it all. Help comes from the field of bioinformatics, whose scientists organize and examine masses of data to reveal and extract new information.

Other scientists explore the vast, intertwined networks of factors that sculpt the behavior of whole cells, tissues, or organisms. These complex studies overwhelm traditional"reductionist" techniques that hammer out the roles of individual molecules. The solution is to use an entirely new method — computer modeling, which harnesses approaches from computer science, math, physics, and engineering.

To support such computer-based strategies, NIGMS launched its newest component, the Center for Bioinformatics and Computational Biology (CBCB). This Center supports theoretical and quantitative studies of biological networks and dynamic processes.

Fields that already have a strong quantitative backbone — such as population biology, biophysics, biophysical chemistry, structural biology, and drug design — are supported within the NIGMS scientific divisions. The new Center focuses instead on recruiting investigators with mathematical and computational expertise to study processes like cell division, cell motility and mechanics, the assembly and dynamics of macromolecular complexes, signal transduction, metabolism, gene expression, and pattern formation in embryogenesis.

The Center supports multidisciplinary collaborations, sponsors workshops and meetings, defines the Institute's needs for database development and applications, and collaborates with other NIH components and Federal agencies in developing policies in this area.

Mining and Modeling Biology's Complexities
The research supported by CBCB focuses on a wide variety of systems, organisms, and biological processes. One example is work led by Douglas Lauffenburger of the Massachusetts Institute of Technology. His research team borrows an approach from electrical engineering to examine how a cell's behavior is governed by biochemical reactions on its surface. Using a signal processing circuit model, the scientists are able to explain, predict, and intentionally alter the behavior of cells.

Another researcher, Garrett Odell of the University of Washington, uses computer simulation to study the molecular gymnastics required for cells to move and change shape. His group focuses on protein molecules called actin and tubulin that assemble into long filaments, and myosin molecules, which chug like railcars along actin filaments.

The team's goal is to understand how all these molecules work together to mold cells into tissues in developing embryos. Because errors in early development underlie a variety of cancers and birth defects, understanding molecular details of the process may help treat or prevent these disorders.

Physicist Stanislas Leibler of Rockefeller University seeks to capture mathematically how myriad factors, including genes, interacting molecules, and environmental signals, weave together to control a cell's behavior. He and his collaborators focus on how bacteria respond to chemical changes in their environment — a process called bacterial chemotaxis that allows the bacteria to move toward food and away from noxious chemicals. Their models are designed to predict the bacteria's behavior under different conditions. To complement and refine this theoretical approach, they conduct laboratory experiments in which they alter the internal biochemistry of E. coli bacteria and examine how these changes affect the speed or accuracy of the bacteria's movement. Surprisingly, even genetically identical bacteria behave very differently. Leiber's group seeks to figure out why.

The researchers expect that their studies will reveal the connections between, and relative influence of, the network of factors that control bacterial chemotaxis. These "design principles" will in turn advance our understanding of many other biological signaling pathways.

So how do scientists develop the skills and get the experience to become leaders in their fields? In a word, training.

NIGMS trains more students to become scientists than any other component of NIH. The Institute has special programs to increase the number of physician-scientists and to encourage students from underrepresented minority groups to pursue biomedical research careers. For most of its training programs, NIGMS provides funds to universities and other institutions, which then select their own trainees.

The areas in which NIGMS supports training roughly mirror the fields in which it supports research. These include genetics, pharmacology, cell biology, biochemistry, computational biology, and biotechnology. A complete list of NIGMS training and fellowship programs is available at http://www.nigms.nih.gov/Training/Mechanisms/.