Systems biology models cells in vivo
11 May 2011 by Evoluted New Media
Living systems are more complicated than cultured cells, and while computer modelling has been used to describe the behaviour of cells in a dish, scientists have steered clear of modelling cells inside a living animal.
Living systems are more complicated than cultured cells, and while computer modelling has been used to describe the behaviour of cells in a dish, scientists have steered clear of modelling cells inside a living animal.
|
Mouse intestinal epithelial cells – researchers have shown how such cells respond to TNF Courtesy of MIT News Office |
That is until now – researchers from MIT and Massachusetts General Hospital (MGH) have successfully created a computational model that describes how intestinal cells in mice respond to a natural chemical called tumour necrosis factor (TNF).
TNF has been shown to play a central role in intestinal inflammation and provokes one of two possible responses in intestinal epithelial cells – cell death or cell proliferation. Chronic inflammation can lead to inflammatory bowel disease and potentially cancer.
Systems biology has grown dramatically in the last decade and focuses on how the components of a biological system interact to produce the behaviour of that system. The approach captures the complexity of living systems through computer modelling of many variables, for example the amount of certain proteins found inside cells and the resulting behaviour.
Researchers obtained the data they needed by treating normal mice with TNF and determining whether the cells proliferated or died. The cell’s fate depended on their location – cells in the ileum proliferated while cells in the duodenum died.
“The multi-faceted result would likely not have been seen in a lab dish,” said Douglas Lauffenburger, head of the MIT department of biological engineering. “In cell culture, you would have gotten one or the other.”
Researchers also correlated the diverse outcomes with the activities of more than a dozen proteins found in the cells, allowing them to determine how the outcome depended on the quantitative combination of key signalling pathways and how the outcome might be affected by drug treatment.
“You’re not likely to explain most diseases in terms of one genetic deficit or one molecular impairment,” Lauffenburger said. “You need to understand how many molecular components, working in concert, give rise to how cells and tissues are formed – either properly or improperly.”
The researchers are now trying to determine what factors in the intestinal cells’ environments influence the cells the way they do, and are studying how genetic mutations might alter the cells’ responses.
