Paving the way for proteomics
A field of study that is only about five years old is beginning to blossom at Pacific Northwest National Laboratory. Proteomics is the systematic study of patterns of proteins expressed in living organisms.
"Where the genome is the blueprint of all the possible proteins within a cell, the proteome is the subset of those proteins that actually are made and change within a cell over time as the cells respond to their surrounding environment or disease," said Karin Rodland, a lead scientist in PNNL's proteomics program.
Rodland explained that there are two related and interdependent components of proteomics research at PNNL. The first has to do with developing uniquely powerful analytical tools that are being applied to help the U.S. Department of Energy. For example, the researchers at DOE's William R. Wiley Environmental Molecular Sciences Laboratory (EMSL) are working to identify all the proteins expressed by organisms such as Deinococcus radiodurans, one of the most radiation-resistant organisms known. As more is learned about how the proteins in this organism react to radioactivity, researchers might know more about how to protect people from exposure to radiation or reverse its effects.
The second component is more focused on human biology and health-related research. "As we track what groups of proteins do, we can begin to discover the disruptive influences that may cause problems in the cells," Rodland said. "Identifying the proteins that cause problems and removing or repairing them could help cure or prevent diseases such as cancer." By using proteomic tools developed at EMSL, researchers can compare proteins in normal cells with those of diseased cells.
In one project funded by the Department of Defense, PNNL's Rick Zangar is looking for early biomarkers of breast cancer by analyzing fluid discharged from the breast. In time, this research could lead to the development of a clinical test where a protein chip, or assay, could quickly determine if a patient is expressing the biomarkers for breast cancer.
Another research project being proposed would compare the proteins expressed on the cell surface in different stages of ovarian cancer. By determining the differences between early-stage ovarian cancer with a cure rate of 95 percent and late-stage cancer that has only a 15 percent survival rate, researchers may be able to detect ovarian cancer earlier and keep it from progressing.
"These projects are examples of how the national laboratories push the frontiers," Rodland said. "We're developing the tools and starting the transition of applying those tools to meet real needs."
One such tool involves instrumentation that measures the mass of peptide fragments, or accurate mass tags, with the level of accuracy needed for protein identification. Researchers at EMSL are leading the world in developing these instruments. By identifying accurate mass tags, a proteome can be characterized with more confidence and with higher throughput than achieved by other methods.
In diagnostics, the future could lead to protein chips that could be used to quickly identify specific cancers based on blood or saliva samples. "You could identify the type of cancer, how far it progressed and match it with an extensive collection of drugs tailored specifically for the kind of tumor a patient may have," Rodland said. "Researchers around the world will jump on this approach, addressing one cancer at a time, until we begin to make a dent in the problem of targeting therapeutics specifically to the patient's cancer."
www.biomolecular.org/research/proteomics/
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www.pnl.gov/news/back/proteomics.htm