The Game of Life, On Life

Light interacts with and controls biological systems in diverse and fascinating ways. Our eyes are made up of thousands of cells that respond to light, sending signals to our brain as light in different colors and shapes moves across them. Photosynthetic cells are full of receptors that can sense and respond to many wavelengths of light, allowing cells to absorb light for photosynthesis, but also to move towards areas of more sunlight and know when the seasons are changing. Synthetic biology takes these light-responsive systems as parts that can be recombined, shuffled and integrated into other systems to create novel biological behaviors. Biological engineers have designed bacteria that respond to light and turn color, essentially making living film (pictured on the right), while others have engineered neurons to fire when illuminated with a laser.

These examples use proteins that are stuck on the cell membrane, activating cascades inside the cell when light shines on them. Through clever engineering, the surface proteins can be made to activate an arbitrary interior cascade, allowing light to control whatever biological process the engineer chooses. Other cellular light-responsive systems that have become popular in synthetic biology more recently (featured in both the Harvard and MIT iGEM projects last summer) involve proteins from inside plant cells that change shape depending on the wavelength of light shining on them. Under red light, PhyB can bind very tightly to its partner protein, PIF. When the red light switches to infrared, PhyB changes shape and PIF falls off. These light-switchable proteins can be fused to other proteins that will be brought along for the ride.

An awesome paper from the Cell Propulsion Lab at UCSF last year demonstrated some of the amazing things that can happen when you engineer these systems in living cells. They fused PhyB to a protein that is always attached to the membrane, and PIF to a yellow fluorescent protein. When they shined a red laser on a cell expressing these fusion proteins, they could watch the fluorescent protein become stuck to the membrane and then falling off in infrared light using a fluorescence microscope. The binding was engineered to be so tight and the switching so fast, they were able to display Conway's game of life on the surface of a single mouse cell by alternately shining lasers and infrared light on specific "pixels," patches on the membrane surface just microns across. The videos are available in the supplementary info without a subscription and they are really incredible:

They went on to fuse proteins that affect the crawling motion of cells to PhyB and PIF, creating cells that could crawl along a slide following a laser pointer. The ability to control complex cellular behaviors with simple inputs is amazing and incredibly powerful, allowing us to easily and tightly control novel biological behaviors to create potentially useful things and, importantly, to better understand how biology works.