Science

New protein maps give insight into the human body

Surprise: Some proteins are made by bits of DNA that used to be considered 'junk,' researchers find
New protein maps may someday help doctors identify damaged tissues and treat cancers

More than a decade has passed since scientists completed the Human Genome Project, a worldwide effort to decode our DNA. That DNA sequence contains instructions for making all of the proteins that our bodies need to function.

Now researchers have cataloged the vast majority of those proteins, creating a dynamic map of the human body called the proteome.

The findings, described in a pair of studies published this week in the journal Nature, identify the proteins encoded in roughly 17,000 to 18,000 of the estimated 21,000 human genes — including some proteins made by bits of DNA that were once considered "junk."

These rough drafts of a protein map, which are publicly available online, could help scientists better understand how the body is supposed to work.

"It's a remarkable achievement," said Michael Washburn, a proteomics scientist at the Stowers Institute for Medical Research in Kansas City, Mo., who was not involved in the research.

If DNA carries the blueprint for life, then proteins are the construction workers responsible for putting those plans into action. Built from strings of amino acids, they hustle around the body transporting molecules, facilitating chemical reactions, making repairs and carrying out a vast array of essential tasks.

Hemoglobin, for instance, delivers oxygenated blood to tissues throughout the body. Insulin regulates how the body metabolizes carbohydrates and fats. Antibodies enable the immune system to attack intruding bacteria and viruses.

"If it weren't for proteins, there'd be no life," Washburn said.

That's why researchers set out to build a near-complete list of human proteins.

But they knew that mapping the proteome would be much more complicated than mapping the genome.

For one thing, reading the instructions held in DNA doesn't necessarily tell you what the protein's properties will be, because the amino acids can interact in extremely complex ways.

For another, although a complete set of DNA can be found in every cell in the body, different proteins pop up in different abundances in different places. That's why neurons in the brain look and act very different from hepatocytes in the liver and cardiomyocytes that make up heart muscle.

So both teams of researchers — one based in Germany, the other made up of scientists from the United States and India — collected tissues from a variety of sources. Between them, they analyzed proteins from blood, ovary, kidney, brain, heart and liver cells. They also looked at proteins found in fetal tissue and proteins extracted from cancer cells.

They chemically snipped the long, complex proteins into smaller units called peptides. Then they analyzed the amino acids within the peptides using an instrument called a mass spectrometer.

Altogether, the team led by Akhilesh Pandey, a molecular biologist at Johns Hopkins University in Baltimore, found proteins made by about 84% of the known protein-coding genes. The other team, led by proteomics scientist Bernhard Kuster of the Technical University of Munich, found proteins made by about 92%.

Because the two teams went about their work in slightly different ways, the researchers expect that the overall protein count will rise when they compare their data sets.

Both sets of searchers found a few proteins that matched up to regions of DNA that weren't thought to include protein-coding genes. (Many such regions used to be thought of as "junk DNA," but that idea has fallen out of fashion.)

"They're genes that have been overlooked," Kuster said. "That was very surprising."

Pandey said the new maps would help scientists identify patterns in the body — and perhaps, down the line, enable doctors to identify damaged tissues based on the proteins sloughing off them and washing into the bloodstream. Such a map might even help doctors come up with the best treatment for a cancer based on its particular protein profile.

To understand these biomarkers of disease or damage, researchers first will have to understand the protein makeup of a healthy person.

Although it may seem that very little of the proteome remains to be sequenced, that's far from the case, researchers said.

The proteome map is far from static — in fact, it's more like a dynamic heat map that must keep up with changing conditions, Pandey said. When we eat or exercise, for example, our bodies respond by producing different combinations of proteins.

This means it will be a long time before researchers fully understand the human proteome, Pandey said. "Basically, the proteome will never be done."

amina.khan@latimes.com

Copyright © 2014, Los Angeles Times
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