Multi-Scale Structure and Dynamics of Visual Signaling in Drosophila Photoreceptor Cells

A general problem in science today is how to understand complex systems. An emerging and promising approach makes the bold assumption that complex systems adhere to particular design principles. The power of this is that design principles by definition impose an intuitive nature on a system by presupposing purpose. Existing studies have fruitfully shown the application of engineering principles in biology, but biological systems have many distinct features, particularly due to evolution. In this work, I used Drosophila phototransduction, a well-studied sensory system renowned for its high performance, to search for evolutionary design principles. I focused on three levels of structure in the system: compartmentalization of molecules into microvilli, modularity of dynamic scaffolding by InaD, and functional integration within a single domain of InaD. Using rigorous quantitative measurement and theory with an evolutionary mindset, I uncovered intuitive, simplifying design principles at each level: Microvilli are used to build fast, homogeneous signaling compartments whose dimensions are constrained by these requirements. Dynamic scaffolding is a modular feature of InaD PDZs 4-5 which have been co-inherited in many scaffolds. Within PDZ5, ligand binding and oxidation of the domain are linked through pairwise coupling with a conformational equilibrium—a generic property found in all proteins—and not each other. These results show that this approach can be successful in revealing novel design principles in complex evolved systems.