The first genome fully mapped was that of a worm called C. elegans. And though scientists are still unraveling the mystery of how everything works, the worm is surprisingly similar to the human genetic structure, though it's a much less complex creature.

That similarity is why researchers from around the world, including the University of Utah, believe that learning how cellular proteins interact in the worm will tell them how individual proteins in humans function. That could help explain how cancer and other developmental processes occur.

Scientists from Utah, Massachusetts, France and Belgium have collaborated on a study to see which proteins in the worm physically touch each other. The study was recently featured in the online issue of Science.

For the project, Huntsman Cancer Institute researcher Susan Mango, an associate professor in the Department of Oncological Sciences at the U.'s School of Medicine, looked at the digestive tract, which is generally what her lab studies. "We've been trying to discover which genes are important to make the digestive tract and to let it function," she said.

But where traditionally researchers have looked at genes or proteins individually, they're trying to learn from large networks of them at once. Study lead scientist Marc Vidal, Dana-Farber Cancer Institute, expanded the use of a tool called the yeast two-hybrid (Y2H) method so the researchers can look at protein interactions for thousands of genes at a time. It's the equivalent of learning from a forest, rather than just a tree, Mango said.

C. elegans is a very simple, tiny animal that lives in soil, "but for scientists, it's great," Mango said. "On the one hand, it has a lot of organs and tissues that humans have, but scaled down so it's much simpler and easier to study. You can get answers with a worm much faster, and the hope is — and it has turned out generally to be true — the way things work in worms is how they work in more complicated animals.

"What we've been trying to do is discover the genes that are important to make the digestive tract and let it function" in the worm, she said.

"Now that we have the full genomic sequence for worms and humans, people are devising ways to look at huge networks at a time. It gives us a different perspective than we had on how a cell works or an organ is put together. It provides avenues for following up different genes and proteins. And it's very fast," she said.

In cells, proteins contact others and work together to accomplish a task. Some proteins are well understood and others aren't. If you have a protein about which little or nothing is known and you can see that it binds to another protein that is better understood, "it gives you insight into process," she said. Researchers can create what are basically "interaction maps" to seek connections that have thus far eluded them.

The U.'s contribution to the study involved using a technique called microarray to identify genes that are expressed in the worm's digestive tract, then Vidal examined the proteins bound to those. They also "knocked out" certain genes to see what would happen.

A related area of study at the U. centers on cell development. "One big question in developmental biology, which is what I do, is how does cell specialization progress over time and is it reversible? Can you regenerate a structure that's been damaged?" Mango said.

The earliest cells in a young embryo have the potential to become many, many things. That's the basis of ongoing stem cell research. But over time, in development, that potential becomes progressively more restricted.

Dividing, growing, regenerating are all choices that cells make. Birth defects "are poor choices by cells." Cancer is a cellular choice as well. But there's much more to understand about cell development and protein interactions before it will have an impact on illnesses like cancer, she said.


E-mail: lois@desnews.com