Combining Engineering and Biology

The MIT researchers focused on a pathway in yeast that controls cells' response to a specific change in the environment. The resulting model is “the simplest model you can ever reduce these systems to,” said Alexander van Oudenaarden, W.M. Keck Career Development Professor in Biomedical Engineering and Associate Professor of Physics.

Quantitative modeling of a biological pathway normally involves intense computer simulations to crunch all available data on the dozens of relevant reactions in the pathway, producing a detailed interaction map. Alternatively, a complex system can be treated as a “black box,” where you don't know what's happening inside but can figure it out by analyzing the system's response to periodic inputs. This approach is widely used in the engineering disciplines but has rarely been applied to analyze biological pathways.

In the new study, the “black box” is a pathway involving at least 50 reactions. The pathway is activated when yeast cells are exposed to a change in the osmotic pressure of their environment, for example, when salt is added to their growth media. The researchers controlled the inputs – the bursts of salt - and measured output – the activity of Hog1 kinase. They exposed the cells to salt bursts of varying frequency, then compared those inputs with the resulting Hog1 activity.

Using that data and standard methods from systems engineering, they came up with two differential equations that describe the three major feedback loops in the pathway: one that takes action almost immediately and is independent of the kinase Hog1, and two feedbacks - one fast and one slow - that are controlled by Hog1.; Source: Massachusetts Institute of Technology