Using Optogenetics to Dissect Information Processing in Cell Signaling Networks
Living cells are highly sophisticated information processing devices that must sense diverse inputs and make complex decisions. In recent years our understanding of cellular decision making has been advanced by the development of elegant ways to measure pathway outputs. Conversely, however, we are severely limited in our ability to control the inputs we deliver to the cell in space and time. I will describe how optogenetic techniques can be used to overcome this challenge, allowing the experimentalist to control the exact combinations, dynamics, and spatial locations of pathway activity in live cells. Applying optogenetics to mammalian growth factor signaling revealed that the Ras/Erk module is able to accurately sense and transmit a huge range of steady-state and dynamic inputs, suggesting that downstream processes may be important for discriminating different classes of inputs. Using a light-based screen, we were able to uncover a number of these dynamics-sensitive downstream modules, including a cell-cell communication circuit acting through IL-6 family cytokines.