Computing Signals

OK after making fun of System Biologists out comes Peter Sorger's latest paper in Cell.

In this paper, Sorger's team collected almost 8000 intracellular measurements (they collected some of the data directly and got the rest from the literature - I'll have to check on that) plugged it into an algorithm or a ...

... compact representation of the entire compendium by using discriminant partial least squares regression (DPLSR; Janes et al., 2004). A DPLSR map was created such that the signaling proteins and cytokines were projected onto a set of "principal components" that maximized covariation between the time-integrated signaling profiles and the corresponding cytokine treatment ...

Um ... yeah ...

So what did they find?

Their computational analysis predicted that when Tumor Necrosis Factor (TNF a hormone that is thought to trigger cell death) is added to cells, epithelial growth factor (EGF) signals get activated that counter-act the cell death pathway. EGF signals in turn activate Interleukin-1 (IL-1) signals that promote cell death.

But how does these signaling pathways cross-talk? It turns out that if you throw TNF onto cells to activate the TNF receptor, cells secrete transforming growth factor (TGF) within 15-30 min. TGF in turn autostimulates the cell's EGF receptors resulting in the production and secretion of IL-1 4-8 hr later and IL-1ra 8-12 hr later. IL-1 stimulates and IL-1ra inhibits the interleukin receptor.

So this complicated interplay of signals was deciphered through a Systems Biology approach.

(And in related news - I've been told that Peter Sorger is moving from MIT to Harvard's Systems Biology department. I hope that his move away from the Lauffenburger lab doesn't hurt Sorger's ability to produce excellent Systems Biology work.)

Ref: Kevin A. Janes, Suzanne Gaudet, John G. Albeck, Ulrik B. Nielsen, Douglas A. Lauffenburger and Peter K. Sorger. The Response of Human Epithelial Cells to TNF Involves an Inducible Autocrine Cascade. Cell (06) 124:1225-1239

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