Proteomics: The Human Genome

by Food and Drug Administration (FDA)

While the genes that compose the human genome provide the building blocks for who we are, it's the proteins that do the heavy lifting within the body.

"A protein is like a mini-machine in your body that makes it work," says Rick Edmondson, Ph.D., a senior researcher at the Food and Drug Administration's National Center for Toxicological Research (NCTR). "Your muscles are made of protein. If you think that you want to pick up a cup, the proteins are the ones actually doing the work.

"Proteins break down the food you eat so it can be absorbed in a form your body can use. Proteins in your brain store your thoughts. Basically, proteins are what we are made of," says Edmondson, who oversees the NCTR's Center for Proteomics.

The completed human genome published in 2003 contained between 30,000 and 35,000 genes, far fewer than the 100,000 genes predicted by scientists when the project began in earnest in the mid-1990s.

Those genes contain the recipes for between 1 million and 5 million proteins. Many of those proteins are not new proteins. Some proteins become other proteins. Others are modified during metabolism and other body functions.

"When some proteins do their job, they may break down to another protein," says Raj K. Puri, M.D., Ph.D., director of the Division of Cellular and Gene Therapies at the FDA's Center for Biologics Evaluation and Research. "Then they may have another job to do."

All in all, it's the elegant, continuous interaction of your genes, proteins, and other biochemical actions inside your body that make you — you.

What Is Proteomics?

Nearly every cell in your body has two complete sets of chromosomes — one from your mother and another from your father. Deoxyribonucleic acid — DNA for short — makes up the core of those chromosomes and serves as the blueprint for another nucleic acid called ribonucleic acid (RNA). The areas of DNA that provide the code for RNA are organized into genes, and most genes contain information for making a specific protein.

The process of building RNA molecules using the DNA sequence code as a guide is called transcription. In turn, RNA molecules direct the building of specific cellular proteins from amino acids in a process called translation. These proteins directly regulate cellular functions including cell growth, responses to activity outside the cell, and cell death.

Proteins also play a role in most diseases.

Put simply, proteomics is the study of the function of all expressed proteins. Initially, the term was used to describe the set of proteins coded for in the genome. But now proteomics is used by many to describe not only all the proteins of any given cell, but also the interactions, modifications, and much of what happens after gene expression.

"You can think of proteomics as profiling changes," says Daniel Casciano, Ph.D., director of the NCTR. "We are using proteomics for pattern recognition. We're taking protein samples — typically blood serum and sometimes urine — and looking for changes between a normal state and a disease state."

Much of the research being done at the NCTR centers on identifying the telltale molecular changes called biomarkers that are characteristic of a disease.

"Finding the protein or proteins associated with a disease or adverse event is going to lead to a much earlier identification of biomarkers," says Edmondson. "Someday, we'll be able to identify proteins in your body signaling that something is occurring long before the symptoms are visible."

For example, prostate-specific antigen (PSA) is a protein produced in a man's prostate gland. A test developed to measure the level of PSA in the blood allows physicians to use this biomarker to help diagnose prostate cancer. PSA levels, alone, do not provide enough information to distinguish between cancer and benign prostate conditions, but high levels of PSA may indicate that further tests for prostate cancer are warranted.

Edmondson's work focuses on pattern recognition — looking for changes in protein expression in blood serum taken from healthy and diseased tissue.

"It's sort of like 'Sesame Street' — which one is most like the other?" says Edmondson.

The Big Picture

Proteomics provides the opportunity for researchers to get a global view of the communications and always-changing events within a cell, instead of focusing on the more static singular gene, says Puri. "Proteins inside the cell talk to each other," he says. "They interact." This nearly constant back-and-forth between cells is called "cell signaling circuitry."

"It's a new way of looking at the biological process," according to Puri. Indeed. The term "proteome" was coined in 1994 by Marc Wilkins, an Australian postdoctoral fellow. Wilkins defined proteome as all the proteins being expressed in a given cell at a given time. He called the study of the proteome, proteomics.

Proteomics, like the other "-omics," is a young science. Many of the tools needed to identify and purify proteins were developed during the 1980s and early 1990s. And, while the progress in mapping the human genome has some thinking about doing the same with the proteome, the technology to do so doesn't exist — at least not yet.

But that hasn't slowed researchers armed with high-throughput systems capable of mining mountains of data in search of the defective proteins responsible for diabetes, arthritis, Alzheimer's, cancer and a host of other maladies.

"It's a different way of looking at things," says Puri. "If you can correlate gene expression with protein expression, you have a very powerful technology."

About the Author

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