Our paper conclusively established that a novel mammalian photopigment melanopsin can perceive light and trigger a signaling cascade leading to change in membrane potential. The study also suggested key steps in this signaling process and concluded that the process is distinct from vertebrate rhodopsin phototransduction.

The paper combines a number of simple methods, long used by biologists, to demonstrate some key properties of melanopsin and its signaling cascade. The approach may be useful to researchers interested in testing the photosensitive role of novel opsin-like molecules and to those interested in learning the mechanism of activation of the TRPC class of ion channels. The discovery of the melanopsin phototransduction pathway also introduces several molecules and steps in our overall understanding of circadian biology.

Whether we travel over time zones, work on a night shift, or experience different seasons, our body clocks automatically readjust to the new lighting schedule. Intriguingly, individuals who are blind can still readjust their internal clock to new lighting. Animals can do the same. Very little was known about the light sensor or the process that resets this internal clock. The paper shows how a new light sensor present in only a few hundred cells of our eye can sense light and send this information via chemical signals. Interestingly, this light-sensing process by melanopsin is very different from that used by the traditional light sensors which are responsible for vision.

I have long been interested in understanding how organisms measure time on a daily basis and how they readjust this timing device with change in day-length or with time-displacement, such as jet travel or shift-work. Using a genetic approach, we had demonstrated the dominant role of melanopsin in light-entrainment of the circadian clock. That led us to explore ways to find whether melanopsin is in fact a functional photopigment and, if so, how does it function? In collaboration with the expert electrophysiologist Tim Jegla of the Genomics Institute of the Novartis Research Foundation and Surendra Nayak—an excellent GPCR biochemist—we put together a novel approach to find the melanopsin signaling process.