Biological Control: The Versatile Ways in Which Cells Use Feedback Loops

Abstract

In 1939, Walter Cannon wrote in his book The wisdom of the Body : “The living being is an agency of such sort that each disturbing influence induces by itself the calling forth of compensatory activity to neutralize or repair the disturbance”. Since this remarkable statement that postulates the use of feedback control to support life, we have come to appreciate that the use of feedback loops is ubiquitous at every level of biological organization, from the gene to the ecosystem. In this talk, we focus on examples that demonstrate the versatile roles and functions that feedback loops play in cells, and also discuss the need for tools, technologies and mathematical frameworks for studying biological feedback control. In the first part of this talk, we discuss examples of the use for layered feedback loops to produce oscillations and biological rhythms. We describe the use of mathematical tools that led to establishing and analyzing these phenomena. We also discuss the use of feedback in producing multi-stability, with examples illustrating biological switches. In the second part of this talk, we discuss more nuanced use of feedback to modulate quantitatively the activity of biological pathways. We will present examples that include the use of feedback to dynamically shift the dose response of a pathway or to modulate the variability of pathway activity to induce different distributions of behaviors across a population. In the third part of this talk, we discuss available tools for studying and measuring feedback activity in cellular pathways, and illustrate the difficulty inherent in these endeavors. We motivate the need for new tools, both experimental and computational, to study biological feedback. As a closing statement, we will pose the nascent challenge of designing feedback control systems using biomolecules for many biotechnological applications.