Thursday, May 26, 2011

MAPK: Feedback Amplifier, Part I

Originally Posted on  by hsauro

A recent paper by Sturm et al., reports results that support the hypothesis that the MAPK cascade acts as a negative feedback amplifier.

The systems biology literature is full of reviews and articles about oscillators and bistable systems and very little else other than Uri Alon et al’s refreshingly unique work on feedforward systems. An alien race, upon reading the literature, would most likely believe that the only thing biochemical networks can do is oscillate, show bistability, and perhaps a little ultrasensitivity. This is probably because many of the modelers and theoreticians in systems biology are unaware of the possible signal processing capabilities offered by the engineering field. For example, an engineer looking at the MAPK cascade would probably immediately think of a negative feedback amplifier. Mention the word negative feedback amplifier to a systems biologist however and you’re likely to get a blank stare. So what is a negative feedback amplifier? Let’s start with some recent history.

Industrial Revolution

Probably the most famous modern device that employed negative feedback was the governor. Thomas Mead in 1787 took out a patent on a device that could regulate the speed of windmill sails. His idea was to measure the speed of the mill by the centrifugal motion of a revolving pendulum and use this to regulate the position of the sail. Very shortly afterward in early 1788, James Watt is told of this device in a letter from his partner, Matthew Boulton. Watt recognizes the utility of the governor as a device to regulate the new steam engines that were rapidly becoming an important source of new power for the industrial revolution. The image below illustrates an engraving of a governor from an early book entitled ”An Elementary Treatise on Stream and the Steam-engine by Clark and Sewell published in 1892.

The operation of the governor is simple (See Figure below), its purpose is to maintain the speed of a rotating engine at a constant predetermined value in spite of changes in load and steam pressure. The vertical axle of the governor is connected to the rotation of the steam engine. As the steam engine, for one reason or another, speeds up, the rotation increases, thereby causing the centrifugal pendulums to swing out. A linkage transmits this motion to the stream valve in such a manner that the flow of steam is reduced thus slowing down the engine. If the engine slows down too much, as a result of a sudden load, the flyweights will swing back and the steam value is opened so that the steam engine can accelerate. The governor was a highly successful device and it is estimated that by 1868, 75,000 governors where in operation (A History of Control Engineering, 1800-1930 By Stuart Bennett, 1979).

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