The National Institutes of Health is on the verge of choosing six institutions or companies in the US to become part of the Molecular Libraries and Screening Center Network, a component of the NIH’s Roadmap for biomedical research.
But in the meantime, the NIH announced earlier this month that it is soliciting novel assays — a significant percentage of which are expected to be cell-based — to arm the MLSCN with the most current screening technologies available.
According to a program announcement released on March 1, the NIH is “inviting investigators to seek access for their [high-throughput screening] assays to the MLSCN, [which] intends to screen 100 to 200 HTS assays per year to fully utilize the capacity of the screening centers.”
The full program announcement can be seen here.
Although letters of intent for the first round of awards were due last week, the application receipt deadline is April 13. However, last week, Ingrid Li, coordinator for the MLSCN program told Inside Bioassays that researchers wishing to submit their assays for consideration can still do so by sending their applications directly to the MLSCN program office.
In addition, the assay solicitation process will be ongoing, Li said. The program will continue through May 2006, with additional application deadline dates of Sept. 14, 2005; Jan. 18, 2006; and May 18, 2006. In each case, the letter of intent is due approximately a month prior.
“The reason that the date is so short this time is that we wanted to have a set of assays that could come in and be selected by the end of the [NIH] fiscal year, so before Oct. 1,” Linda Brady, team leader for the MLSCN program, told Inside Bioassays. “And also, we wanted to have a set of assays to be considered for implementation within the MLSCN, which we anticipate will be in place later this year.”
The program announcement also states that up to $3,000 will be available for each award to cover assay implementation costs, including providing required reagents and travel to the screening centers.
“Although the primary function of this process is to select assays for implementation in the MLSCN,” the program announcement continues, “the mechanism to be used for application, review, and selection will be the Small Research Grant R03 award in a form that provides limited funding for one year.”
However, MLSCN program officials recently told Inside Bioassays that the relatively small monetary award is not the real draw for researchers that might be interested in submitting their assays for consideration.
“Another function of the MLSCN is that it will be able to provide optimization chemistry support,” Li said. “If the investigator identifies a novel target of some biological significance, and then they are looking for a small molecule to modulate that process — these will be places where we can provide that type of service.”
Brady added that researchers would be able to take advantage of the repository of approximately half a million small molecules that the NIH is currently building.
“It’s offering an opportunity to an academic investigator that has a really interesting assay, and they need a small-molecule probe to do their research, but they don’t have high-throughput screening capabilities,” Brady explained. “These assays can be peer-reviewed and taken into the network, and a compound library run through the assay to generate a hit.
“The hits will then be optimized to make them useful as a probe, and the probes will be made available to the scientific community,” Brady added. “So the investigator that submitted the assay will eventually, we hope, have a probe that they can use in their research. But they won’t have put in the effort to get that probe — it was something that the screening center will have done as a service.”
Such a scenario may be attractive to academic and other non-profit scientists, but will the arrangement attract industry scientists to submit their assays for consideration? Li and Brady think so, especially for smaller biotech companies that do not have their own small-molecule repositories. Many of these companies currently rely on industry partners for such a resource.
“The only thing that we’re asking is that people don’t try to protect any intellectual property that comes out of here,” Brady said. “That’s sort of the price for going into the screening centers network.
The MLSCN is soliciting a wide variety of assays for as wide a variety of targets. According to the program announcement, these are roughly broken down into four areas:
• Target-based biochemical assays including enzymatic assays, and receptor-ligand binding assays;
• Cell-based assays including functional assays, reporter gene assays, and phenotypic assays for cellular processes and pathway analysis or model organisms such as yeast, C. elegans, zebrafish, et cetera;
• Assays for non-traditional targets of interest, including transcription factors, nucleic acids, multimeric proteins, membrane proteins, polymorphic gene products, sub-cellular processes, post-transcriptional editing or splicing of gene products, and protein or RNA stabilization;
• Other assays, including those for metabolism, bioavailability, toxicity, and blood-brain barrier permeability.
In addition to the obvious second category, the final two categories can be construed as having a significant cell-based, small-organism, or small-animal component.
Li and Brady were reluctant to place specific emphasis on any one category, but did say that if the response to last year’s RFA, entitled “Assay Development for High-Throughput Molecular Screening,” (which can be seen here) serves as any guide, there will be a large number of potential cell-based assays, as well as assays for non-traditional targets, especially from the academic side.
“There were 111 applications from the research community, and that can give us a pretty good idea,” Li said. “It seems like the percentage of cell-based assays is much higher there than in industry, [which] does not prefer to use cell-based assays. It’s true that a lot of phenotypic assays rely on cell-based assays, though, and all the screening centers will have the capability to implement [them].” Li added.
“When you look at the percentage of druggable targets that industry focuses on, we didn’t see that same balance reflected in the applications that came in to the assay-development RFA,” Brady added. “There was much more of a focus on non-traditional, non-druggable targets. So we actually expect a lot more innovative targets that may not have been tried in an industry setting coming in; at least, that would be our hope.”
Screening Centers Coming Soon
The MLSCN panel is currently wrapping up the unenviable task of whittling down 36 applications that it received for membership in the MLSCN to six, Brady said.
Brady said that the decisions are likely to be made by the end of this month. “From that point I think it might take another one or two months for our grant-management people to process all the awards and get everything in place for making the awards. So we’re really hoping, say, around May at the latest for the awards to be issued.”
It wasn’t clear if the MLSCN would be in place before the Oct. 1 fiscal deadline, but such a scenario seems to make sense, considering the rush to solicit assays that can be used in the MLSCN before that same deadline.
Brady said that interest has come from both the public and private sectors, with about one-third of the applications coming from the latter.
“We covered a broad range of expertise and skills in molecular screening,” she said. “Several of the potential centers are really high-industry centers.”