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NIH Releases Screening Instrumentation RFA as Part of Biomedical Research Map

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The National Institutes of Health is seeking applications for novel bioassay technologies.

A little after two years since rolling out its “roadmap” for biomedical research, the institutes are finishing the roadwork on one of the largest initiatives in this plan — the Molecular Libraries and Imaging project.

On July 13, the agency unveiled the Request For Application for the last of four grant and funding opportunities that fall under this initiative — this one for the development of screening instrumentation. According to the RFA, which can be seen here, letters of intent are due by September 22, and the application receipt date will be a month later.

The types of technology sought by the NIH span the realm of biological assays, and include innovative microfluidics and lab-on-a-chip technologies; improved high-content cell-based assay formats; innovative methods for data acquisition and management; and novel screening system integration methods.

Bradley Ozenberger of the division of extramural research at the National Human Genome Research Institute, who is heading the instrumentation initiative, cited the importance of miniaturization in assay and instrumentation development.

“This is important with these small molecule libraries,” Ozenberger said. “The NIH will have its own repository of synthetic chemicals and natural products, and these are in limited supply. So miniaturization is always important — not only to increase efficiency, but also to conserve reagents.”

But Ozenberger also stressed that the NIH wants to see “substantial innovation from applicants. We purposefully try to not give too many or too specific examples, because we want to leave it out there for researchers’ creativity,” he said.

In addition, Ozenberger said that the agency would consider both brand new instrumentation platforms and proposals that seek to improve upon existing technologies.

“We actually debated that quite a bit,” Ozenberger said. “It’s a difficult line to walk. It’s going to be somewhat dependent on [the] response to this RFA. We are looking for innovation, but we are also looking for a practical device at the end of the grant.”

For example, he said, there currently aren’t massively high-throughput approaches for large whole-genome gene expression as an HTS tool. “So if somebody can bring in that device which can integrate a gene chip into that kind of approach, that would be something we would want to see,” he said. But, Ozenberger added, particularly in the arenas of miniaturization and lab-on-chip technologies, “people are working on one platform that will go from cell culture to screening to phenotypic readouts all on a very small scale. That’s not going to be readily integrated with current robotics and may require a whole stand-alone system, so that would be great as well.”

The instrumentation funding availability is quite generous relative to its counterparts in the Molecular Libraries and Imaging initiative.

The instrumentation arm, according to Ozenberger, is operating under the R01 grant mechanism, under which investigator-initiated research receives a large amount of funding — typically over $500,000. In this case, Ozenberger said, the NIH has budgeted $4 million a year with the anticipation of funding four to six grants for up to four years.

Meanwhile, the other three grant and funding opportunities in the Molecular Libraries and Imaging initiative — the screening centers network, assay development, and high-resolution probes for cellular imaging — are moving along.

Screening Centers

The first of these funding opportunities to close will be the screening centers, for which candidates had to submit a letter of intent by yesterday. The application due date is August 24. The goal of this initiative is to create a network of small molecule screening centers to assist in screening the NIH’s large repository of small molecules against known and novel therapeutic targets.

“The targets and assays are fairly well developed,” said Linda Brady, the screening centers project team leader. “But the centers would actually implement them to a higher level of throughput, and then test the compounds that we have in the repository through the assay, and then make the data available publicly.”

Brady said that although it is a bit early, the agency has already seen eight to ten letters from groups that are planning to put in instrumentation, and that “we expect that we will receive 10 to 15 more. We had about 22 or 24 responses to an earlier request for information, so we’re anticipating almost that many groups,” she said. Furthermore, she said, the NIH held a technical assistance workshop on June 2 that was well-attended by both the academic and private sectors.

Some companies are already courting customers at potential centers. Two weeks ago, Carl Zeiss — along with technology partner and high-content screening pioneer Cellomics — announced its intent to promote the use of its instrumentation and services to academic-affiliated screening center candidates. (See article in this issue, Cellomics and Zeiss Sniff Out Customers At Potential NIH-Funded Screening Centers).

Other companies have already secured big instrumentation contracts: San Diego-based Kalypsys in June had its suite of ultra-high throughput screening technology selected by the first screening center — the government-affiliated Chemical Genomics Center — to the tune of a possible $30 million. (See Inside Bioassays, 7/13/2004).

But Brady made it clear that the NIH was not endorsing the use of any particular screening technologies. “We’ll be looking for cell-based, biochemical, organism-based, and high-content or phenotypic assays,” she said. “But we’re really leaving it up to the scientific community to make its own selections of all of the resources. We’re not endorsing anything in particular, but I know that there are a lot of private sector organizations that are very interested in our initiative because it’s going to involve academic investigators more in conducting this kind of research.”

Brady said that the agency has allocated approximately $20 million in funding for the first year with the goal of selecting anywhere from six to eight centers. In the first year of funding, she said, the NIH will award each center $1 million in direct costs with $500,000 allowed for equipment, with an incremental increase to $2 million in the second year and $3 million in the third year.

“Because that represents direct costs instead of total costs,” she said, “[$20 million] will probably be for seven or eight centers because it’s going to be hard for us to predict what indirect costs will be and how much equipment individual centers might ask for.”

Integration

The other two funding opportunities in the Molecular Libraries and Imaging initiative are for the development of high-resolution probes for cellular imaging — for which the letter of intent is due Oct. 20 and applications are due Nov. 20 — and for the development of high-throughput screening assays.

The HTS screening assay funding opportunity is ongoing, Brady said, but has already seen a tremendous response, having received 120 applications since it was announced on Feb. 25. These applications will be the first of the RFAs to be reviewed, on Aug. 5 and 6, she said.

Throughout this entire process, the NIH will provide plenty of opportunity for interaction between the four arms of the initiative, with the would-be screening centers acting as hubs for such interplay.

“Through these centers we’re hoping to bring these technologies and different areas together somewhat,” Ozenberger said. “For example, the intramural center will have bench space for people to come in with assays or instrumentation, and spend time and see what the needs are and how their own technologies or methodologies can fit in.

“We don’t want that to be limiting,” Ozenberger added. “We are looking for generally applicable instrumentation … but there will be an opportunity for grantees to come to these centers and make sure their system integrates.”

—BB

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