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NIH Adopts Trans-Institute Proteomics Initiative Plan with Its $2.1B Roadmap

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The $2.1 billion Roadmap for Medical Research that NIH director Elias Zerhouni introduced at a Sept. 30 press conference will include three proteomics-focused trans-NIH initiatives, including one that establishes several National Technology Centers for Networks and Pathways, according to NIH officials and released materials.

The announcement came less than two months after a recommendation from the Board on Life Sciences of the National Academies’ that the NIH implement trans-NIH initiatives for proteomics and other areas of science that often involve cross-disciplinary research (see PM 8-8-03). According to Zerhouni, the NIH has been working on developing the roadmap’s initiatives for the last 12 months, well before the report came out. He said at the press conference that “no organization the size of the NIH should be without a process for reevaluating its structure.”

The roadmap is divided into three main themes, each of which has several trans-NIH initiatives associated with it: New Pathways to Discovery, Research Teams of the Future, and Re-engineering the Clinical Research Enterprise. The first theme has the most relevance to proteomics, and includes all three proteomics-focused initiatives.

Associated with each team are several task forces whose job it was to create programs to implement the theme. One of these, the Building Blocks, Pathways, and Networks Implementation Group, developed two of the proteomics initiatives: the National Technology Centers for Networks and Pathways, and the Standards for Proteomics and Meta-bolomics/Assessment of Critical Reagents for Proteomics. The Structural Biology Implementation Group developed the third: Protein Production Facilities.

The grant for the National Technology Centers for Networks and Pathways, or TCNPs — which was released concurrently with the roadmap announcement — will be composed of two to four centers over five years, with $7.4 million earmarked for the first year. Applicants can ask for up to $2 million in the first year in direct costs.

As one of only four RFAs put out immediately following the NIH press conference, the grant establishing the TCNPs will be a guinea pig for the roadmap’s trans-NIH scheme. Douglas Sheeley, director of the Division of Biomedical Technology at the National Center for Research Resources and the current leader of the cross-institute team that will manage the grant, said that as a trans-NIH initiative, the TCNPs will receive funding and administrative support from all of the NIH’s many institutes. While the NCRR will take the lead in the early days of the grant administration — having so far taken charge of writing and publishing the RFA — [the program] “is going to be a cooperative effort between many institutes and we’re going to try to be as inclusive as we can,” according to Sheeley. He said that there was “substantial input” from all of the institutes when constructing the program. He mentioned in particular the participation of the NIDDK, NIAID, NHLBI, NHGRI, NIGMS, NIEHS, and NIDA, but emphasized that this list was far from complete.

Proteomics is a good model for the roadmap design, said NIDDK director Alan Spiegel, also a director of the Building Blocks implementation group. “The NCI, NIAID, NHLBI, and NIDDK all have major initiatives in proteomics. But these are primarily focused on taking existing technologies and applying them to the disease, organs, and problems of mission-specific interests of those institutes,” he said. “The concept of the roadmap is for the NIH to push the technology further.” Spiegel said that when composing the roadmap, all the institute directors had agreed to set aside the $2.1 billion from the “top of the NIH budget.” This was a positive move, Spiegel said, because it made the financial burden for trans-NIH initiatives “neutral with respect to the base of individual institutes.”

The TCNPs are being created to focus on developing technologies that can look at dynamic systems of proteins and produce quantitative, spatial, and temporal information at high resolution. “The folks in the Building Blocks, Pathways, and Networks group reached this mutual conclusion that obviously proteomics is an important area for a lot of reasons we both know,” said Sheeley. “One of the things we think we’re doing well now [in proteomics] is to look at a complex, take an inventory of the proteins that are there, and take a kind of static snapshot of the system. But that doesn’t tell us a lot about how it’s changing, or which proteins are participating at what times.”

Sheeley said that the main goal of the RFA would be to develop technology that showed the dynamics of a system rather than just cataloging the proteins, and that applicants could focus on different ways to do that, whether that method entailed finding quantitative, spatial, or temporal data — or all three. Sheeley was also purposely vague about what particular technologies the grant was targeting. “We’re deliberately trying not to be too directive about what people propose,” he said. “It’s important for us to communicate the kinds of problems we’re interested in having solved. It’s less important what we think the answers are.” He said that “evolutionary” changes such as improvements in mass specs, as well as “revolutionary changes” that no one has yet foreseen, are both welcome candidates. “What we’re looking for is what’s going to give us the biggest bang for our buck,” he said.

The parameters that the RFA does explicitly set are that the investigators address the three main areas of front end preparation, sample analysis, and informatics; that they work in collaborative teams; that the proposal includes some element of “high risk”; and that their teams address all six “cores” detailed in the RFA. The cores divide the tasks of the groups into thematic parts, including technology development, Driving Biological Projects, and the dissemination of the technology into the community. The DBPs, Sheeley said, “provide a test bed — a challenging problem that couldn’t be solved by other means and that helps them to see if they’re really doing something.”

Spiegel said that the second proteomics initiative — Standards for Proteomics and Metabolomics workshops — would be headed by three institutes: the NIDDK, NCRR and NHGRI. An “appropriate community of investigators” will be selected to advise the NIH during a series of workshops beginning in 2004, and likely following up in 2005. Scientists will discuss issues of standardization and coordination in the areas of data release and reagents. “Of course there's HUPO, and they pay attention to standards. But just as with the genome sequence where there had to be standards in terms of data release and accuracy, here where there's even greater complexity, one really needs standardization so the entire community of investigators can communicate,” Spiegel said.

The Protein Production Facilities initiative will seek to develop fast and reliable methods for producing membrane proteins. An outline of the 28 roadmap initiatives, available here, gives a short explanation.

The TCNP RFA, available here, has an application date of March 16, 2004, but, Sheeley said, “We’re eager to talk to people well in advance of submission.”

— KAM

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