PROTEOMICS PROJECTS
HUPO Plasma Proteome Project: Challenges and future directions During a 2-hour evening workshop at the U.S. HUPO Second Annual Conference held in March, researchers discussed the remaining challenges for the HUPO Plasma Proteome Project (PPP) now that the pilot phase has concluded. According to Gil Omenn, who is a co-chair of PPP and is at the University of Michigan, the project will continue with several working groups. The working groups will likely focus on six missions: developing consensus standard operating procedures (SOPs); identifying or preparing peptide, protein, and plasma reference standards; prioritizing plasma proteins for antibody production or procurement by the HUPO Antibody Initiative (HAI); recruiting several major laboratories that have experience with advanced technologies to a nalyze plasma samples and share the results; interfacing with disease-oriented and organ-based proteomics initiatives; and sustaining a robust bioinformatics effort to integrate findings from PPP, other HUPO initiatives, and various published works. A major thrust of PPP will be to develop SOPs for specimen collection and handling. Sample collection seems like a straightforward matter, but even slight variations in technique by clinicians who withdraw blood from volunteers or by chemists who analyze the samples could have a large effect on which proteins are identified. According to Omenn, SOP development is particularly important for researchers who
are conducting studies of specific organs or diseases. If protein biomarkers are identified initially in biopsied tissues, then researchers could examine the blood to determine whether these biomarkers are in the circulation. The advantage is that blood tests are much less invasive than biopsies. Omenn says that to make progress on developing blood tests for biomarkers, researchers tallying the proteins in organs should also collect blood samples—something that is not t ypically done. SOPs developed by PPP could help encourage these researchers to collect samples in a standard way. To get the ball rolling, Ruth VanBogelen of Pfizer offered to make the company’s SOPs for specimen collection available to PPP. “Companies in general are eager to see cooperation with the academic sector and across companies on methods and evidence for standardization so that the FDA [U.S. Food and Drug Administration] can develop and issue clear guidance on what would be acceptable methods for submissions” to the agency, says Omenn. In addition to standard protocols, some researchers noted the need for standard plasma reference samples. A lively discussion at the PPP session centered on how a reference standard would be created. “The choice of a [particular] plasma sample for a standard and whether it should have certain proteins spiked into it or whether you should just spike a mixture of nonhuman proteins into test plasmas are all [topics that are] under discussion,” says Omenn. He adds that the U.S. Nation-
al Institute of Standards and Technology and the U.S. National Cancer Institute have hosted meetings on this issue and that PPP will have a working group investigating the options. Another PPP working group will collaborate with the HAI, which is led by Mathias Uhlén of the Royal Institute of Technology (Sweden). The group will recommend that HAI produce or obtain antibodies to certain plasma proteins. As Omenn points out, many decisions must be made regarding antibody production. For example, researchers must choose whether to develop polyclonal antibodies, which recognize many epitopes but are not renewable, or monoclonal antibodies, which recognize only a single epitope but are a renewable resource. Finally, a small group of perhaps six major laboratories will analyze plasma samples with state-of-the-art technologies. For example, Omenn reported that Ruedi Aebersold at ETH Hönggerberg (Switzerland) is developing a “proteotypic” peptide approach in which unique glycopeptides are isolated, and synthetic versions of the peptides are labeled with heavy isotopes. The labeled peptides are then used to identify and quantitate plasma proteins. Various instruments and bioinformatics tools will be tested among PPP investigators as the analyses move forward. Omenn says that the next step for the group is to present the plans to the HUPO Initiatives Committee and the HUPO Executive Committee for review and approval. —Katie Cottingham
GOVERNMENT AND SOCIETY
A new proteomics building for Rutgers Rutgers, the State University of New Jersey, has announced that $55 million of its capital investment funds will be used to construct a new proteomics building scheduled for completion by 2008. Called the Center for Integrative Proteomics Technologies, the building will be located at the university’s Piscataway, N.J., campus and will bring together researchers from several proteomics-related fields under one roof. Many Rutgers researchers are al-
ready involved in proteomics, structural biology, and computational biology as participants in the Northeast Structural Genomics Consortium, the Protein Data Bank, and the BioMaPS Institute for Quantitative Biology, which are all based at the university. Most of the ~14 laboratories will be led by new principal investigators in proteomics, structural biology, and computational biology as part of a current faculty recruitment drive at the school. According to university officials, the three-story building will include
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meeting space for researchers to gather and exchange ideas. Researchers within the walls of the new building may also want to get together with their new neighbors. The building will be located near the new Rutgers Life Sciences Building and the Center for Advanced Biotechnology and Medicine, a collaborative effort of Rutgers and the University of Medicine and Dentistry of New Jersey. This location is prime; the Center for Integrative Proteomics Technologies could help bridge the gap between investigators at the two universities.
