MIT applies engineering approach to studying biologica...( CAMBRIDGE Mass.--An MIT team has use...)

CAMBRIDGE, Mass.--An MIT team has used an engineering approach to show that complex biological systems can be studied with simple models developed by measuring what goes into and out of the system.

Such an approach can give researchers an alternative way to look at the inner workings of a complicated biological system-such as a pathway in a cell-and allow them to study systems in their natural state.

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 and senior author of a paper describing the work in the Jan. 25 issue of Science.

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.

These simulations are difficult to perform and interpret because many model parameters are not or cannot be experimentally measured. Moreover, because there are so many interconnected components in the network, it is difficult to make reliable predictions, said van Oudenaarden.

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. The technique is very general and could be used to study any cellular pathway with measurable inputs and outputs, van Oudenaarden said.

You don't want to open the box, but you want to shake it a little, he said. Comparing the response when you shake it fast to when you shake it slowly reveals important information about whic
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