Eric Schadt, the chief scientific officer at Pacific Biosciences and founder of SAGE Bionetworks, in a lecture on the emerging field of systems biology on Nov. 24, proposed a broad approach that takes into account the complexity of living organisms. The lecture in the Jordan Hall of Science titled: “An integrative biology approach to reverse engineering living systems,” showed the limits of more narrowly focused approaches in a field that has application to disease treatment and drug discovery, renewable energy, and adequate food production. Michael Ferdig, professor of Biological Sciences, arranged the visit.
Schadt said that, despite expectations, the mapping of the human genome and human genetic variation has shown limited value in predicting disease. That’s because factors that affect the physiological states associated with disease include genetic perturbations, genetics and environmental forces, not genes alone, and the fundamental components are organized into a hierarchy of networks that define living systems – not linear pathways. Beyond sequencing and genotyping, he said, “We need better methods of integrating these different dimensions of data. Can we take all this information and integrate it into a model that is capable of predicting future states of the system?”
Schadt, who has degrees in math, computer science, molecular biology and biomathematics, brings together the fields of biology, mathematics and supercomputing. He describes his integrative approach as a new super high resolution microscope that, combined with the massive data generation capabilities of Pacific Bioscience’s newest sequencing technology, will allow researchers to establish cause-effect relationships for a single enzyme molecule. For example, he discovered a concentration of genes predictive for diabetes in one subnetwork in mice with Type 2 diabetes and showed that changes in that network affect other networks related to the disease.
The broader view is in some ways a return to the focus on physiology that was typical in medicine before molecular biology led to a focus on single genes. “Molecular biology revolutionized ability to look at individual genes and proteins, and physiology was pushed to the side,” Schadt said. “It’s largely failed because there was no way to hook up single-gene views to physiological states. Networks are intermediate between genes and physiology.”