Xudong Qiu held a month-long vigil in a room lit only by red lights and the beam of a microscope. The windows and doors were sealed with blackout paper, and his only companion was a single human kidney cell.
Qiu, a postdoctoral research associate in neuroscience, was waiting for the cell to produce a tiny electrical current, the missing evidence needed to prove his hypothesis and catapult his name into the most respected scientific journals in the world.
Now, over a year later, Qiu has published his first paper in Nature trumpeting his discovery that melanopsin is the molecule responsible for sensing light in ipRGCs, strange eye cells that were discovered only three years ago.
Like rods and cones, ipRGCs are a type of light-sensitive cell in the mammalian eye. They translate incoming light into an electrical signal that is sent to the brain. But these cells are not responsible for vision the way rod and cone cells are. Instead, ipRGCs transmit information about overall light intensity directly to the part of the brain that controls our circadian rhythm, the internal clock that primarily regulates when we wake up and fall asleep.
Professor of Medical Science David Berson, who discovered the cells in 2002, said the circadian rhythm "is like the clock chip in your computer," which can keep time all on its own but sometimes needs to be reset. The ipRGC cells make sure that your internal clock remains synchronized to the 24-hour day-night cycle.
Berson said many researchers suspected that melanopsin was the molecule responsible for sensing light, but Qiu, under Berson's guidance, was the first to prove it. Three other researchers published papers with similar conclusions the same month.
To prove melanopsin's role in sensing light, Qiu used genetic engineering techniques to make kidney cells that produced the protein. The kidney cells are not normally responsive to light, but when they produce melanopsin, they suddenly begin to behave like photosensitive cells. Like ipRGCs, they generate a very small electrical current after being stimulated by light.
Because the cells respond to light, Qiu had to block out all daylight in his lab. However, he knew that melanopsin was not activated by red light, so he put a red filter over his desk lamp, providing just enough light to work by.
It took an entire month of testing three cells per day, day after day, before Qiu saw the first electrical signal produced by a kidney cell. Then he set about discovering exactly what color of light the molecule did respond to, checking hundreds of cells over several months.
"I would feel very happy if I could get one (to work) every day," he said.
His research has generated a lot of interest in the scientific community because of the novelty of the photoreceptor system. "Science tends to run in fads," Berson said. "The story is so different, there is still a lot of buzz."
While melanopsin is found in the human eye, it is also found in regions deep in the brains of many other animals. Bird and lizards are synchronized to the day-night cycle without the use of their eyes, Berson said.
In fact, light passes through many animals' skulls to penetrate the area of the brain which controls the circadian rhythm. In mammals, the skull is too thick to allow light to pass through, so we have outsourced the same job to our eyes, with a "main line signal going right from the retina to the clock," he said.
Now that melanopsin's role in this system has been defined, Berson and Qiu are trying to discover the other molecules in the cell responsible for creating the electrical signal. They suspect it is generated by tiny channels in the cell's membrane that are structurally very similar to those found in the invertebrate eye.
"It's a little fly characteristic in the human," Berson said with a grin.
