Dr. James Priess shares Gruber Genetics Prize

Fred Hutchinson Cancer Research Center developmental biologist Dr. James Priess shares the 2022 Gruber Genetics Prize, awarded by the Gruber Foundation at Yale University. The $500,000 prize, which Priess shares with Drs. Ruth Lehmann and Geraldine Seydoux, recognizes the researchers’ pioneering discoveries regarding molecular mechanisms involved in embryonic development.

“Any biologist absolutely hopes what they do will impact human health, though often in basic sciences the way forward is to first understand the fundamental biology,” said Priess. 

He discovered genes and cellular processes that allow the fertilized eggs of tiny worms called nematodes, one of the major animal models studied by developmental biologists, to transform into complex, multi-cellular animals. 

“Jim really understands the power of genetics and he’s very creative,” said molecular biologist and Hutch colleague Dr. Susan Parkhurst. “When you put that combination together, it's allowed him to take really innovative approaches to address challenging questions. His work is really beautiful and has stood the test of time: Time after time he’s made seminal discoveries that have set the foundation for his field.”

Priess said a large part of his initial studies on Caenorhabditis elegans, the nematode researchers use to study many fundamental biological processes, simply involved watching its eggs develop in real time, about 12 hours. 

"I did this countless times,” he said.   

It only takes a couple of hours for the cells to start organizing into a worm-like shape, and muscles start contracting about six hours in.

“Each of the cell division cycles takes about 15 minutes, which gives you a forced pause to think over what you just saw,” he said.   

At the time, Priess was in graduate school and not much was known about the molecules or processes controlling development. Some scientists argued that cells’ environment controlled how they developed, while others argued that it came down to a cell’s ancestry. There was evidence that in C. elegans, developing cells followed programming that was present from the get-go, supporting the ancestry hypothesis. There was an intense effort by several labs to understand the mechanisms of cell programming. 

As a postdoctoral fellow, Priess showed that the current view was incomplete, and that early cell fates were determined by both interactions between cells and programming within cells. But to understand development more deeply, he needed to identify the molecules involved, and genetics seemed like the way forward, he said. In a time when cloning and characterizing genes required an enormous investment of time and resources, scientists needed a compelling reason to study any specific mutant. 

Priess developed a rapid screening method to identify essential genes provided by the mother to the early embryo that relied on his expertise in worm anatomy. 

“By looking at their patterns and then doing genetic combinations of mutants, we could put together a story that made sense and then build on that,” Priess said. “That launched a lot of subsequent studies that we did in my own laboratory at Fred Hutch.”

He didn’t make the discoveries alone, Priess stressed.

“I have always worked at the bench and been fortunate to work alongside a spectacular list of creative postdoctoral fellows, graduate students, and technicians,” he said.

These include researchers who trained in his lab, including then-postdocs Drs. Bruce Bowerman, Craig Mello and Rueyling Lin, and then-graduate student Dr. Bruce Draper. Priess has also maintained a long-term collaboration with Dr. Ken Kemphues at Cornell University.

"How our DNA allows a single fertilized egg cell to generate the vast complexity of our bodies is one of the greatest mysteries of life. By starting to chart this course near its beginning, Lehmann, Priess and Seydoux have demonstrated that embryonic development is within our powers to fully understand," said Dr. Allan Spradling, professor at the Carnegie Institution/HHMI and chair of the Selection Advisory Board, in the foundation’s press release.

With Seydoux and Lehman, Priess will receive the award at a ceremony later this year.