• Credit: Lance Hayashida
11/20/2012 14:45:50

An Eye for Science: In the Lab of Markus Meister

Take one look around Markus Meister's new lab and office space on the top floor of the Beckman Behavioral Biology building, and you can tell that he has an eye for detail. Curving, luminescent walls change color every few seconds, wrapping around lab space and giving a warm glow to the open, airy offices that line the east wall. A giant picture of neurons serves as wallpaper, and a column is wrapped in an image from the inside of a retina. And while he may have picked up some tips from his architect wife to help direct the design of his lab, Meister is the true visionary—a biologist studying the details of the eye.

"Since we study the visual system, light is a natural interest for me," says Meister, of the lab he helped plan before joining the Caltech faculty in July. "The architecture team responded to this in so many creative ways. They even installed windows inside the lab space, so that researchers at the bench could see straight through the offices to the nature outside."

Exactly how our eyes process those images of the world around us forms the basis of Meister's research. In particular, he investigates the circuits of nerve cells in the retina—a light-sensitive tissue that lines the inner surface of your eyeball and essentially captures images as they come in through the cornea and lens at the front of your eye. A traditional view of the retina is that it acts like the film in a camera, simply absorbing light and then sending a signal directly to the brain about the image you are viewing.

But Meister, who earned his PhD at Caltech in 1987 and was the Tarr Professor of Molecular and Cellular Biology at Harvard before moving back west, sees things a bit differently.

"There is a lot of preprocessing that occurs in the retina, so the signal that gets sent to the brain ultimately is quite different from the raw image that is projected onto the retina by the lens in your eye," he says. "And it's not just one kind of processing. There are on the order of 20 different ways in which the retina manipulates a raw image and then sends those results onto the brain through the optic nerve. An ongoing puzzle is trying to figure out how that is possible with the limited circuitry that exists in the retina."

Meister and his lab are dedicated to finding new clues to help decode that puzzle. In a recent study, published in Nature Neuroscience, he and Hiroki Asari, a postdoctoral scholar in biology at Caltech, studied the connections between particular cells within the retina. Their specific discovery, he explains, has to do with the associations between bipolar cells, which are the neurons in the middle of the retina, and ganglion cells, which are the very last neurons in the retina that send signals to the brain. What they found is that the connections between these bipolar cells and ganglion cells are much more diverse than had been expected.

"Each upstream bipolar cell can make different neural circuits to do particular kinds of computations before it sends signals to ganglion cells," says Asari, who began his postdoctoral work at Harvard and moved to Caltech with the Meister lab.

The team was also able to show that in many cases, the processing of information in the retina involves amacrine cells, a type of cell in the eye that seems to be involved in fine-tuning the properties of individual bipolar cell actions.

"It's a little bit like electronics, where you have a transistor—one wire controlling the connection between two other wires—that is absolutely central to everything," says Meister. "In a way, this connection between the amacrine cells and the bipolar cell and the ganglion cell looks a little bit like a transistor, in that the amacrine cell can control how the signal flows from the bipolar to the ganglion cell. That's an analogy that I think will help us understand the intricacy of the signal flow in the retina. A goal that we have is to ultimately understand these neural circuits in the same way that we understand electronic circuits."

The next step in this particular line of research is to figure out exactly where the amacrine cells are making their impact on bipolar cells. They believe most of the action happens at the synapses, the connection points between the cells. Studying this area requires new technology to get a good look at the tiny connectors. Luckily, Meister's new lab includes an in-house shop room—complete with a milling machine, a band saw, and other power tools needed to build things like microscopes.

"In this lab, we're doing things on many levels—from the giant milling machine all the way down to measurements on the micron scale," says Meister.

He also plans to expand his research focus. The team has started to study the visual behavior of mice, evaluating, for example, the kinds of innate reactions—those that don't require any other knowledge about the environment—they have to certain visual stimuli. Ultimately, the researchers would like to know which of the pathways that come out of the retina control which behaviors, and if they can find a link between the processing of vision that occurs early in the eye and how the animal functions in its environment using its visual system.

"In my new lab at Caltech, I'm trying to branch out further into the visual system to leverage the understanding we have about the front end—namely processing in the retina—to better understand the different actions that occur in the brain, all the way to certain behaviors of the animal that are based on visual stimuli," he says.

Meister says that he's also excited to get back into an environment that's more focused on math, physics, and engineering—something he hopes to take advantage of at both the faculty/colleague level and the student level.

"Our research subject is one that I feel connects me with so many different areas of science—from molecular genetics to theoretical physics," he explains. "You can rely on a wide range of collaborators and people who are interested in different aspects of the subject. To me, that's been the most satisfying part of my career. I have collaborative projects with neurosurgeons, a theoretical physicist who develops models of visual processing, a particle physicist who builds miniature detector electronics, a molecular genetics expert. These interactions really keep you broadly connected."

And he's hoping to connect to even more people now that he's settled in his Beckman Behavioral Biology lab—even if it's just for a friendly visit.

"I know we're in a remote corner of the building at the north end of the top floor, but we try to keep our door open at all times," says Meister. "There are only five people in the lab right now, and it gets kind of lonely. We're going to build the group up, but in the meantime it would be nice if people came to visit us."

Written by Katie Neith