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The art of science

Feb. 1, 2001
Roundworm C. elegans

The roundworm C. elegans is a model system for the study of early development. The adult worm, shown here with three embryos, is composed of 959 cells and is about half an inch in length.

Image courtesy Jim Priess

A worm might seem an unlikely hybrid of art and science. But examine a few of Dr. Jim Priess' neon images of developing C. elegans in Cell or Nature, and you'll have to peek at the cover of the magazine to convince yourself you are looking at a scientific journal and not a modern-art periodical.

A former art student, Priess sees art in science each day as he watches these microscopic creatures transform from single cells into organisms that can move, mate and respond to chemicals using a primitive sense of smell - with a total of only 959 cells.

Displaying innovative approaches for studying this model system, Priess' work has led to new insights into how development proceeds in a variety of organisms.

As early as the first cell division after fertilization, the worm - like many other organisms - must sketch out a rudimentary blueprint for development.

As though born into a particular caste, most cells are programmed for only one fate, chosen to become muscle or intestinal cells of the body (soma), for example. In contrast, other cells, called germ cells, produce the eggs and sperm and thus eventually reproduce the entire body with its vast array of cell types.

"In distinguishing the germ cells from somatic cells," Priess said, "what we're really asking is, what keeps cells totipotent?"

The ability of a cell to be totipotent - to possess the naivete required to develop into any type of specialized cell - is a hallmark of germ cells and a property that is established during the earliest stages of development.

Even before the fertilized egg undergoes its first cell division, molecules have been sifted and sorted to different parts of the egg so that the first division creates two cells with unequal contents and, subsequently, unequal futures.

It's a problem that has fascinated - and stymied - biologists for decades.

Germ-cell determinants

"Scientists have known for a long time - in a variety of organisms - that determinants for the germ cells are set aside during the first few cell divisions of the embryo," Priess said.

But the identity of those determinants remained elusive until the Priess laboratory's discovery in 1996 of PIE-1, a protein found exclusively in cells destined to become germ cells.

Using a combination of sophisticated microscopy and techniques for visualizing proteins with fluorescent tags, Priess transforms invisible determinants like PIE-1 into vivid cellular landscapes that have helped other scientists interpret long-standing mysteries of early development.

"Jim has blown open some areas in germ-cell specification that have been black boxes for a long time," said Dr. Judith Kimble, a developmental biologist at the University of Wisconsin at Madison.

Key discovery

"His identification of PIE-1 was a key discovery - really the first gene of its kind to be identified. People had been looking for something like this for about 25 years."

Dr. Mark Groudine, Basic Sciences Division director, said Priess' novel approach for studying early embryogenesis played a key role in his hiring in 1988.

"It was clear from the earliest stages in his career that Jim had a knack for posing fascinating questions and devising innovative approaches to answer them," Groudine said.

"Jim was the major force in moving the analysis of early C. elegans embryogenesis from descriptive and experimental embryology into the molecular arena, and his work has led to new insights into how development proceeds in many organisms. Much of the most interesting and important work in the field continues to come from Jim's lab and from the labs of investigators who have trained with him."

More recently, Priess has turned his attention to another factor affecting germ cell specification known as P granules, dense bodies that have been observed in cells fated to become germ cells.

"P granules have been observed under the microscope for a long time as a component of germ cells, but it hasn't been known what they are or how they function," he said.

Priess refers to PIE-1 as a permissive factor, one that enables cells to respond to germ-cell determinants, possibly to molecules like P granules. Current studies in his lab will help reveal whether there is a relationship between between PIE-1 and P granules, he said.

His work has important implications for human development and disease in addition to providing general insights into animal embryogenesis. Human stem cells - those cells that are key to the success of bone-marrow transplants for treating leukemia and other blood disorders - must also retain the potential to spawn a variety of more specialized cell types, and thus are analogous to germ cells.

Although many initial observations have been made in the fruit fly Drosophila, the worm offers a number of distinct advantages for studies of cell-fate determination.

Thanks to concerted efforts of prescient researchers as early as the 1960s, C. elegans has been elevated in stature from a mere soil dweller to a pin-up model for the study of development. The tiny roundworm, a fraction of an inch in length, is a member of the elite group of organisms whose genomes have been completely sequenced. More remarkable, because it has what is known as an invariant body plan, the origin of each of the worm's 959 cells - from the time it is a newly fertilized egg until it reaches adulthood - has been determined by a painstaking microscopic reconstruction of its somatic blueprint.

"Even every nerve synapse has been mapped out," Priess said. "There is no other multicellular organism about which so much is known."

At a time when many molecular biologists spend much of their day manipulating DNA and purifying proteins, Priess finds that a visual connection with a complete organism is undeniably appealing.

"It's absolutely amazing to watch embryonic development," he said.

Priess has parlayed his fascination with C. elegans into a remarkably productive career, making advances not only in germ-cell determination but also in elucidating the cellular basis for how tissues and organs acquire their characteristic shape.

Humans have reproducible left-right asymmetries in the placement and shape of their organs. The Priess lab has recently uncovered how left-right asymmetry is generated within the intestine in C. elegans, allowing them to ask whether there are parallel mechanisms in human development.

Hughes recognition

His achievements in the field of embryonic development were recognized by the Howard Hughes Medical Institute, which selected him as one of its prestigious investigators in 1994.

Priess, a native Kansan, had no intention of becoming a scientist, enrolling in college as an art major. Intrigued by a classmate's organic chemistry text - "I couldn't believe the size of it, filled with equations and symbols which at that time were incomprehensible to me" - he decided to sign up for a chemistry class, ultimately choosing study of science over art.

After immersing himself in other science classes followed by a summer of laboratory research, Priess proceeded directly to graduate studies in biology at the University of Colorado.

Introduced to the visual appeal of the worm by a fellow graduate student, Priess began dissertation research in worm embryonic development with Dr. David Hirsh.

He completed postdoctoral studies at the Medical Research Council in Cambridge, England, with Dr. John Sulston, a pioneer of the effort to make the worm a model system by determining its complete cell lineage and helping to initiate its genome project, before joining the Hutch's Basic Sciences Division in 1988.

Priess credits his productivity to the excellent scientists he's been able to attract to his lab.

"There is an incredible synergism that's allowed us to be so productive," he said.

That, and Priess' flair for the visual, has turned a calling into a craft.

Fred Hutchinson Cancer Research Center is a world leader in research to prevent, detect and treat cancer and other life-threatening diseases.