KU researcher studies worms to help understand human kidney disease

LAWRENCE -- Matthew Buechner, assistant professor of molecular biosciences at the University of Kansas, is learning about human kidney disease from an unlikely source -- a worm so small it doesn't even have a kidney.

Buechner and his colleagues have found that the tiny roundworm Caenorhabditis elegans contains proteins remarkably similar to those that malfunction in polycystic kidney disease, or PKD, which can cause the fist-sized organ to balloon to the dimensions of a football. By studying these proteins, they hope to better understand how the proteins operate in people and how absence of these proteins causes the disease.

Surprisingly, Buechner said, the big evolutionary distance between worms and humans can make information obtained from the worms especially valuable.

"It is useful to compare the same genes from humans and distant creatures because that gives you a hint as to where the very basic core of the gene is," he said. "The areas that are similar between the worms and humans are likely to be the areas most crucial to the function of that protein."

Buechner and his colleagues presented the results of their discovery at the October 2001 meeting of the American Society of Nephrology.

In PKD, some of the kidney's tiny blood-filtering tubes, called nephrons, swell into large, fluid-filled cysts. A normal nephron is thinner than a human hair and about as long as the thumb. A nephron afflicted with PKD may expand into a cyst the size of a marble or even a baseball. Eventually, the cysts break free and clog the kidney, causing it to fail. The only treatment is replacement of the damaged organ.

According to the National Institutes of Health, about 500,000 Americans have the disease. It is the most common serious genetic illness in the country, affecting more people than muscular dystrophy, cystic fibrosis, ALS, and sickle-cell anemia combined. Despite its frequency, Buechner said, PKD is not well-known because people do not feel its effects until relatively late in life.

"You don't even know you have it until you start having pain in your back from your kidney enlarging in your 30s or 40s or even later," he said. "It's a serious disease, but a very subtle disease."

Mutations in one of two genes cause the disease, but no one knows why the proteins made by the faulty genes cause cysts. Buechner hopes to change that by studying the protein from the threadlike, soil-dwelling roundworm, which is just big enough to see without a microscope.

"Understanding what is happening with this protein in worms will give us a better understanding of what is happening in humans," he said. "From the resemblance of the proteins, we predict that a lot of the things that are happening in worm cells also happen in human cells."

Despite their structural similarity, the worm and human proteins have very different jobs. In humans, the proteins control the diameter of the nephrons and are found throughout the kidney and elsewhere in the body. In worms, the proteins have a sensory role and are found only in the nervous system of males. They help the males find the vulvas of their hermaphrodite partners (there are no females) during mating.

It may seem strange that such similar proteins can have such divergent tasks. However, Buechner believes the proteins function in similar ways as they go about those tasks. In both worms and humans, the proteins reside in the membranes that mark a cell's outer boundary. Also, in both worms and humans, part of the protein projects out from the membrane. These projections help male worms sense a vulva, but in humans their function is unknown.