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NIH Prepares to Build RNAi Facility To Support Genome-Wide Screening

The National Institutes of Health has begun preparations to establish an RNAi facility to provide intramural researchers with access to the equipment and expertise necessary to conduct genome-wide RNAi screens in mammalian cells, RNAi News has learned.
The facility “is going to work as a collaborative [resource] for doing RNAi assay development, screening, and initial follow up,” Christopher Austin, director of the NIH Chemical Genomics Center who is overseeing the creation of the RNAi facility, told RNAi News last week.
“In this way, it is very similar to what the NCGC does with small molecules” in helping investigators develop and optimize their assays for screening, conduct the screens and related informatics analyses, then perform follow-up screens on promising leads, he added. “Then, we collaborate with the PI … to do the downstream biology required to get the quality publications and the kind of groundbreaking results you want.”
But Austin cautioned that the RNAi facility is still in the planning stages, and that it won’t likely be accepting project proposals from the general NIH research community before 2010.
“All of those issues of governance, how projects are going to get selected, what the outcomes are going to be, [and] how many people there are going to be [at the facility, have] not been worked out,” he said. At the same time, the specific ways in which the RNAi facility will be funded remains uncertain since, as part of the NCGC, it will be supported by all of the NIH’s institutes.
“Whenever you have an organization [that] has as its mission to do projects across the spectrum of biology, and therefore across the spectrum of all the categorical NIH institutes … it’s a wonderful thing” as it can act as a sort of crossroad for all the various aspects of biology, he said.
“But that [also] means the governance is non-trivial because all of the institutes want to have a role … which they should,” he added. “I would say that by the end of this year we will have worked all of those things out,” he added.
If this timeline proves accurate, the RNAi facility will likely spend most of 2009 running a handful of pilot assays and then a few select projects from NIH researchers in a sort of beta-testing period.
“We plan to use those as our guinea-pig assays through a positive control, if you will, to work out all the bugs in the system [that] will inevitably happen,” Austin explained.

“Whenever you publicize something like this, people get their hopes up … that there will be something they can access fully formed immediately. The reality is that to do something … this complicated right is going to take a year or more.”

Once all of that work has been completed, the RNAi facility will be able to begin evaluating proposals for screening experiments from NIH investigators. But while Austin said he expects interest in the facility to be high, he noted that it will likely take some time before the average researcher is ready to take advantage of it.
“These folks never would have … conceptualized experiments to take advantage of this kind of capacity, much less build assays that will be amenable to high-throughput RNAi for genome-wide screening,” he said.
As such, it will take years for researchers to “find out about the power of this approach … [and] learn what the nitty-gritty needs are to convert a lab-based assay [for which] one is using three or four RNAi constructs into something that can be run across a hundred thousand of those in a robotic platform,” Austin said.
This issue is one with which Austin is familiar since he was involved in the establishment of the NCGC almost five years ago.
“When we started small-molecule screening [at the NCGC], people had never had access to this kind of resource outside of a major pharma before, so there was a lag period while investigators began to learn how to put together assays to take advantage of the technology,” he explained. “A huge amount of education [went] into that … [and] I anticipate that is going to be necessary for the RNAi [facility], as well.
“But it’s like any new technology: it’s more complicated than people might thing, but well worth the investment,” he added.
Still, Austin said that at this point the NIH has remained tightlipped about its plan for the RNAi facility “because whenever you publicize something like this, people get their hopes up … that there will be something they can access fully formed immediately. The reality is that to do something … this complicated right is going to take a year or more.
“We’re building the organization for the long haul and [want to] do this in the most rigorous way we can,” he said. “With the blessing … of the powers that be here, we’re going to spend some time doing not only further due diligence with people in the [research] community who have operations that do this sort of thing … but also spend some time doing technology development to make sure that our processes are as robust as possible.”
Here, too, Austin anticipates that the experience building the NCGC will come into play. As it ramps up operations over the coming year, the RNAi facility, which will be housed in new space within the NCGC, is expected to have a dedicated staff of between five and ten people with expertise in a variety of areas including biology, robotics, and informatics.
“But realize that there are 60 people at the NCGC now and [an existing] infrastructure of compound management, robotics, engineering, informatics, biology, administration,” he said. The RNAi facility is “getting grafted onto that infrastructure, so there will be a tremendous amount of support.
“It is not starting from scratch,” he added. “A lot of the issues for RNAi screening are the same as those for small-molecule screening … and those we’ve tackled quite effectively at the NCGC.”
For all the work put into building the NCGC, Austin said that the biggest payoff for the planned RNAi facility will be the “robust” informatics infrastructure that has been put into place.
“Undoubtedly, the limiting [factor] in all high-throughput projects, bar none, after about the first week becomes informatics and deriving information out of the data,” he said. “The conventional approach is to take all of the data, throw it in an Excel spreadsheet, and sort. That is not a scalable approach.
“The time we took to build the informatics infrastructure is going to be a huge advantage in building the RNAi facility,” he said. Additionally, “we have a huge amount of experience with robotics. We all came from various pharmas and biotechs, so we’ve had that experience before. But we really have it now.”
Overall, though, “what we’ve learned and put together is a really nice system to engage with academic investigators who know virtually nothing about screening or the kind of informatics we do, et cetera, and work with them in a mutually dependent relationship [to] establish common goals, learn from each other … and bring real value to this approach.”

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