HARVARD GAZETTE ARCHIVES

Alexander Schier: 'How we go from an egg to a complex animal is really one of the most fascinating questions in biology.' (Staff photos Kris Snibbe/Harvard News Office)

In both fish and humans, the fertilized egg divides repeatedly to form a mass of cells in the early embryo. Cells in different parts of this mass go on to develop into specific kinds of tissue.

It's this process of differentiation - one that occurs over a spectacular 16-hour period in Schier's zebrafish - that has captured his attention.

"The embryo has this program that transforms it into a complex organism with different cell types," Schier said. "How we go from an egg to a complex animal is really one of the most fascinating questions in biology."

Schier, named professor of molecular and cellular biology in September, is not the first to be beguiled by this mystery. Those who came before showed that cells in different locations became particular tissues and that cell-to-cell signaling is likely responsible for that development.

'We don't really know why we have to sleep, why animals have to rest,' Schier says. '[Sleep regulation] is a major question in human health.'

Schier is trying to understand the nature of that signaling, what molecules are responsible, in what concentrations, and, if there are multiple signals, in what order.

"The major challenge now is understanding how these signals are regulated, how they move through the embryo, and how cells respond," Schier said.

Schier began working with zebrafish while a postdoctoral fellow at Harvard-affiliated Massachusetts General Hospital in the early 1990s. Fresh from his doctoral work at the University of Basel in Switzerland, where he also received a bachelor of science degree in cell biology, Schier worked from 1992 to 1996 on a large-scale genetic analysis of zebrafish development.

Zebrafish, though striped as adults, are transparent when embryos, making them attractive to researchers because scientists can literally look inside them and watch how they develop.

In addition to his work on the development of organs in the embryo, Schier has begun using the fish to understand the development of nerves in the head. Specifically, he's targeting the nerves responsible for sensing potentially harmful conditions, such as extreme heat that could lead to a burn.

Though this work is still in what he termed "early days," Schier said that Harvard's strength in neurobiology was one of the reasons that attracted him here.

"It's a very inspiring environment for this kind of research," Schier said.

Schier is taking advantage of the environment to push forward with new projects. In addition to his work on developing nerves, Schier is using his fish model to investigate the phenomenon of sleep.

Though all of us do it, nobody really understands why. The need for sleep varies widely in the animal kingdom, but science hasn't yet figured out why shutting down our waking consciousness for such a large part of every day is so crucial to our well-being.

Schier suspects the need for sleep is linked to repair and restoration and makes us more ready to face the challenges of the coming day.

Schier and members of his lab are observing the fish's behavior. The fish are active for 14 hours per day and go through the zebrafish equivalent of sleep, where their activity is reduced and responses to stimuli slowed, for 10 hours.

Researchers are first observing the fish's normal sleeping behavior and keeping an eye out for mutants - fish who either sleep more or less than others. Once the mutants are identified, the investigation will turn to the genetic code of those fish, where researchers will look for genes that are different from those of "normal" fish.

"We don't really know why we have to sleep, why animals have to rest," Schier said. "[Sleep regulation] is a major question in human health."

Department of Molecular and Cellular Biology Chair Andrew Murray said Schier's diverse interests fit well with the department and said Schier approaches scientific problems with "insight and elegance."

"Alex exemplifies the catholic tastes of the MCB faculty," Murray said. "His own research covers a wide range from how an egg makes an embryo to studying the basic biology of sleep."

Schier completed his zebrafish work at Massachusetts General Hospital in 1996, becoming an assistant professor in the Developmental Genetics Program at New York University School of Medicine's Skirball Institute of Biomolecular Medicine and Department of Cell Biology. He was named an associate professor there in 1999.

Schier credited a college friend with drawing him to biology from his early interest in physics. Schier, who grew up in Switzerland, entered the University of Basel in the early 1980s, when the field of developmental biology was heating up. Groundbreaking work was done by Walter Gehring, a Basel professor who would serve as Schier's adviser.

"You could say nothing happened in developmental biology for 50 years, until embryology, genetics, and molecular biology came together," Schier said. "Once I learned about the new approaches to study life ... I found that really fascinating."

alvin_powell@harvard.edu