Control feedback and cellular responses

Published on November 4, 2014   47 min

Other Talks in the Series: Systems Biology

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This is Frank Doyle. I'm a faculty member in the Department of Chemical Engineering at University of California Santa Barbara. And I'll be giving a lecture on controlled feedback and cellular responses.
I want to start by walking through the origins of this field of systems biology and showing you some profound connections with the field of controls. If one goes back perhaps a century and a half ago, you find the work of Claude Bernard, who was a French physiologist, was the first to coin the term milieu interieur, which we now understand as homeostasis. Walter Cannon was the first to really introduce that English term, homeostasis, as the ability of the body to maintain normal, coordinated, physiologic processes despite disturbances and interruptions to that system. And the last individual here to really play into that field is Norbert Wiener, who's a giant figure in the field of control and communications. And he coined this expression, or this term, cybernetics as a way to envelop all of communications and control, whether it's a natural or a synthetic system.
Here, I'm showing two different circuits that come from the natural world. On the left is the gene regulatory map for a sea urchin. That comes from Eric Davidson's lab. It's probably the most complex gene network that's been put together for a particular cell type. And on the right hand side we have an engineering circuit diagram, in fact, a rather dated, antiquated system, a shortwave radio circuit diagram. But what's quite common to both of these diagrams are the fact that there are numerous feedback relays. There's modular architectures. There's redundancies built in. And these are common to both biological networks, as well as engineered, or synthetic networks. And that's why those of us who live on the engineering side of dynamics, and control, and network theory are bringing new insights and new opportunities for unraveling the kind of biological networks like one sees on the left here. The properties that we're looking to understand, by bringing understanding from feedback control, are things like robustness, the ability of both of these circuits to maintain high levels of performance despite noise, and perturbations, and uncertainty, and really, particularly in biological system, the fact that we have two types of noise which are omnipresent. The first type is external perturbation. So if this is a cell, it might be disturbances in the surrounding tissue. If these are molecules in a cell, it could be disturbances in the interior of the cell. But we also have intrinsic variability built into natural systems, which is the fact that we have low numbers, low copy count, of individual components in the cell, so that reactions, or interactions, between molecules take place in a probabilistic manner. All this together points to the fact that we have tremendously variable, tremendously noisy systems. And in the circuits on the left, the biological circuit, we maintained extraordinary high levels of performance. These organisms have evolved to achieve these remarkable levels of performance. And the price for failure, quite frankly, in the biological realm, is death. So in fact, Mother Nature has created these paradigms that we now, as engineers, are trying to unravel.