New Center for Physiological Proteomics Aims to Transform Diagnosis and Treatment of Disease

By Elliot Wolf

There's little doubt that proteomics—the study of an organism's complete complement of proteins—will transform the life sciences in the years to come.

"To really understand biological processes, we need to understand how proteins function in and around cells since they are the functioning units," said John Yates, a professor in the Scripps Research Institute Department of Physiology who is pushing new frontiers in the proteomics field.

Increasing the excitement surrounding the field is the fact that proteomics offers the possibility of identifying proteins associated with specific diseases. These proteins can then potentially be used as markers for detection or prevention, or as targets for the design of new drugs.

To better address the complex problems in biology and medicine through proteomics, Scripps Research has created a new Center for Physiological Proteomics, headed by Yates. The center will promote collaboration among scientists in the field and act as a dedicated center of excellence, employing state-of-the-art mass spectrometry, powerful bioinformatics tools, and chemical biology approaches to advance the field. The institute is currently seeking private philanthropists to contribute to the new center.

From Breast Cancer to Cystic Fibrosis

Proteomics is often considered the next logical step in the study of biological systems after genomics, but understanding the proteome has its share of challenges.

One is the sheer number of proteins to be identified. The approximately 25,000 genes in the human genome can code for at least ten times as many proteins; in extreme cases, a single gene can code for more than 1,000. Another challenge is that amino acids—the base units of proteins—are so small. Each amino acid is made from anywhere between 7 and 24 atoms. This is far beyond the reach of even the most powerful microscopes. In addition, one organism's proteins differ within each part of the body, stage of the life cycle, and interactions with changing environmental conditions.

But some leaders in the burgeoning field of functional proteomics are making progress at Scripps Research.

Professor Ben Cravatt and his group, for example, have looked at dozens of samples of human tumors from breast cancer patients, and have successfully analyzed them with proteomics. The scientists were able to detect human proteins that may be associated with breast cancer—including some never before associated with the disease.

"We have found some known and novel markers of breast cancer pathogenesis," said Cravatt. "This method could potentially be applied to other human diseases to discover new markers currently evading detection by other methods."

Yates was also the lead scientist in a collaborative project involving 18 researchers at half a dozen laboratories in the United States and Great Britain to determine the proteome of the most deadly form of the malaria pathogen—Plasmodium falciparum.

"This was the first instance that I know of where these proteomics studies have gone along side-by-side with the genome sequencing project," said Yates.

The effort identified the proteins in the single-celled Plasmodium that cause malaria. These efforts will pay huge dividends in global healthcare if even a few of the newly identified proteins lead to the development of new malaria vaccines—and Yates and his colleagues found an unprecedented total of more than 2,400 proteins. Knowing which proteins are expressed by Plasmodium falciparum should help scientists understand how the pathogen causes malaria and, with luck, how to thwart it.

Yates has also applied proteomics in a collaboration with Scripps Research Professor William Balch, which advanced the understanding of the many protein-folding diseases affecting human health, notably cystic fibrosis. The work is providing targets for therapeutic intervention.

Building on a Successful Track Record

Philanthropists making private contributions to the Center for Physiological Proteomics would be providing a "seed" investment in a proven, world-class research program whose work will continue to push the frontiers of biomedical research.

Once leading Scripps Research investigators such as Yates and Cravatt acquire necessary state-of-the-art proteomic technology and expanded scientific staff, they will be positioned to receive larger-scale funding from the National Institutes of Health (NIH). The NIH has made proteomics a priority, but a solid proteomics infrastructure must be in place for researchers to receive such federal funding.

"Understanding the proteome, the structure and function of each protein and the complexities of protein-protein interactions will be critical for developing the most effective diagnostic techniques at early stages to stop disease in its tracks, and treat disease in the future," said Cravatt. "Proteomics is fundamental to translating genomic information into knowledge that will allow us to predict and manage diseases such as cancer, diabetes, and neurodegenerative disorders."

For further information on funding the Center for Physiological Proteomics, please contact Wendy Scott Keeney, vice president of Philanthropy, (858) 784-7083, wkeeney@scripps.edu.

Send comments to: mikaono[at]scripps.edu

"To really understand biological processes, we need to understand how proteins function in and around cells since they are the functioning units."

—John Yates