Kefalov Lab / Projects

We derive most of our information about the world through our visual system by means of rod and cone photoreceptors. The human retina has one type of rod for dim light vision, and three types of cone cells that allow color discrimination. Considering the great importance of cones for our visual experience, surprisingly little is known about the mechanisms that determine their functional properties compared to what we know about rods. Their small number and morphological similarity to rods have made mammalian cones elusive to biochemical and physiological studies. By combining the tools of physiology and molecular biology, which have been invaluable for understanding rod function, we can finally ask questions about cones as well. Why are cones less sensitive than rods and function only under daylight conditions? What are the mechanisms that drive their adaptation to extremely wide range of light intensities compared to rods? What are the mechanisms by which known mutations in cone phototransduction proteins lead to visual disorders?

We are using two different experimental approaches to address these questions. One part of our research focuses on the physiological characterization of mouse cones with the help of single cell recordings. That involves a systematic study of mouse cone function and the role of various phototransduction proteins in determining their properties by using genetically modified animals. We can also use this approach to study the mechanisms by which known mutations of cone phototransduction proteins cause disease. The second part of our research focuses on the differences between rod and cone phototransduction proteins in order to understand how they affect photoreceptor properties. This approach builds on our established understanding of rod phototransduction. It allows the use of rods as a surrogate system to study cone transduction proteins, expressed in transgenic Xenopus rods. The combined studies of knockout, knockin, and transgenic mice together with transgenic Xenopus will be invaluable for understanding how cones function.