Monday, September 19, 2011

Applying control theory to the cell

In a talk about research goals in the systems biology of microbes, Adam Arkin referenced the Internal Model Principle of control theory. Here are a couple definitions.

A regulator for which both internal stability and output regulation are structurally stable properties must utilize feedback of the regulated variable and incorporate in the feedback loop a suitably reduplicated model of the dynamic structure of the exogenous signals which the regulator is required to process.

Towards an Abstract Internal Model Principle Wonham, 1976

That's a mouthful. This one's a little less scary.

Internal Model Principle: control can be achieved only if the control system encapsulates, either implicitly or explicitly, some representation of the process to be controlled.

Lecture notes on Introduction to Robust Control by Ming T. Tham, 2002

Driving this thinking is the discovery that microbes show anticipatory behavior and the associations can be fairly readily entrained and lost in a few generations. Ilias Tagkopoulos and Saeed Tavazoie, in Predictive behavior within microbial genetic networks, demonstrated associative learning through rewiring gene regulatory networks. It turns out that when E. coli senses a shift to mammalian body temperature, it begins the transition to anaerobic metabolism, nicely anticipating the correlated structure of it's environment.

In another example, Amir Mitchell working at Weizmann, showed that yeast anticipates the stages of fermentation in Adaptive prediction of environmental changes by microorganism.

This raises some important questions. How is the internal model encoded within the cell? And how does the cell acquire, parameterize and adjust its internal model over evolutionary time scales? The answers will lead to a deeper understanding of living systems and might even feed new techniques and principles back to control theory.

An interesting challenge will be to experimentally read out the information embedded in the cell's control systems and then the informatics problem of how to represent and work with such things.

Understanding how this works is a prerequisite for re-engineering living systems, otherwise known as synthetic biology, championed by George Church and Drew Endy. This month, by the way, the journal Science has a special issue on synthetic biology.

I'm fascinated by the idea of applying engineering principles to biology - evolved systems, rather than engineered artifacts. Maybe that's because my spaghetti code looks a lot like the messy interconnectedness of biology. Creating software feels organic, rather than wholly predesigned. The engineering of complex software systems tends to be an adaptive evolutionary process. As messy as biology is, modularity naturally emerges. Maybe biology has something to teach us about organizing this chaos.