Rama Ranganathan
Speaker of Workshop 4
Will talk about: Systems-level analysis of a G protein mediated signaling pathway
Dr. Ranganathan is Professor of Pharmacology and holder of the Cecil H. and Ida Green Chair in Biomedical Science at the University of Texas Southwestern Medical Center at Dallas. He is also the Director of the Green Center for Systems Biology. He received his B.S. degree in bioengineering from the University of California, Berkeley, and his M.D. and Ph.D. degrees from the University of California, San Diego, where he studied the mechanisms of visual transduction with Charles Zuker. His postdoctoral work as a Life Sciences Research Foundation fellow was with Roderick MacKinnon at Harvard Medical School on voltage-gated potassium channels and with Joseph Noel at the Salk Institute for Biological Studies on protein x-ray crystallography.
Research Statement:
The Ranganathan laboratory is interested in understanding the structural principles of function in cellular signaling systems and how these systems are built through the process of evolution.
Photoreceptors of Drosophila compound eye employ a G-protein mediated signaling pathway that transduces single photons into transient electrical responses called “quantum bumps” (QB). While most of the molecular components of this pathway are already known, the system level understanding of the mechanism of QB generation has remained elusive. To address this, we developed a quantitative model explaining how QBs emerge from stochastic nonlinear dynamics of the signaling cascade. The model shows that the cascade acts as an “integrate and fire” device, and explains how photoreceptors achieve reliable responses to light while keeping low background in the dark. Further experimental work shows how different functional properties of the QB –size, shape, and probability of occurrence – can be mechanistically decomposed into distinct molecular mechanisms. This analysis provides a foundation for understanding how the essential biological characteristics of visual signaling arise from systems-level structural and dynamical properties of the underlying signaling pathway.
