By Doug Macron
The La Jolla Institute for Allergy and Immunology announced last week that it has received a $12.6 million grant from the National Institutes of Health to establish an RNAi screening center.
"RNAi … is a powerful technology with the potential to transform human health, and we are pleased that the NIH has entrusted us with bringing the first publicly funded RNAi facility to San Diego," Mitchell Kronenberg, LIAI president and CSO, said in a statement.
According to the institute, the center's overall goal will be to host research projects from throughout the San Diego area, although LIAI CTO Stephen Wilson told Gene Silencing News this week that its reach could potentially extend farther once the initiative is up and running.
Part of the institute's mission under the grant is to "invigorate the local scientific community" so that the screening center enhances "more than just our own research," he said. "We'll have partners locally for sure, and possibly nationally or even [internationally] once we get up to speed."
Getting up to speed, Wilson said, will first involve putting together a permanent staff to run the screening facility. "Minimally, we believe there will be enough work for a manager and two full-time technicians," as well as a center director who may or may not come from within LIAI.
With space within the institute already dedicated to the screening center, he said that the facility is expected to be "largely built out" with lab space and equipment by this coming March. As such, a search for the facility manager is expected to get underway shortly.
Wilson noted that he expects LIAI will have to look nationally to fill this role because people with the experience and expertise to run a high-throughput RNAi screening facility and oversee the necessary library maintenance "are not really common."
The center will at first be focused on supporting immunology research, and its first efforts will center around four ongoing projects, being conducted by investigators from LIAI and partner institute Scripps Research Institute, which had heretofore not benefitted from RNAi screening, Wilson said.
"We're going to consolidate enough projects and the right kind of people and equipment [so that] people … can take advantage of large-scale RNAi screens," he said. "It's bringing [the technology] home to immunologists who don’t do this kind of genomics work otherwise."
The first effort "will use a genome-wide siRNA screening to identify missing players in the cellular response to double-stranded RNA, and a focused lentiviral shRNA screen to identify the unknown DNA-binding proteins that initiate responses to foreign microbial" double-stranded DNA, according to the grant's abstract.
The second will screen a library of microRNA-expressing lentiviruses for their ability to abrogate B cell tolerance in vivo. This work is being conducted by Scripps researchers David Nemazee and Changchun Xiao.
Once completed, a third project will apply the outcome of this miRNA screen, along with focused lentiviral shRNA library directed against transcription factors and chromatin-associated proteins, to identify candidates that "influence the decision of CD8 T cells to express markers of effector or memory cell fate," the abstract states.
The fourth project will use the shRNA lentiviral library to "identify transcription factors and chromatin-associated proteins that influence the ability of [CD1D-restricted invariant natural killer T cells] to express the cytokines interleukin-4 and interferon-3, first in cultured human cell lines and later in pooled shRNA screens in vivo," the abstract adds.
Despite its initial emphasis on immunology, "we don't want to … become introspective or limited," Wilson noted. "We want to be as open as possible because, as immunologists, we benefit tremendously from other disciplines.
At the same time, "there is a kind of conservation of mass and energy here, and we need to be careful about not getting too … spread out," he said. In order to strike a balance, LIAI will assemble a committee comprising "thought leaders" within the institute, as well as collaborators at Scripps.
"We'll hear ideas and try to get as involved as possible" in other areas of research being conducted at other institutions, he said.
Wilson said that the $12.6 million NIH grant will support the research staff for the center's first four projects, provide the first year of funding for the center's technical staff, and cover equipment costs.
LIAI, meanwhile, will cover the expense of building out the center's space within the institute.
According to the grant's abstract, the RNAi screening center is expected to be "self-sustaining" within three years.
"By the end of this period, we're hoping there will be other support mechanisms to subsidize the facility," Wilson said. "Federal grants would be the best way to let us keep the program open and collaborate far and wide."
One source of financing that isn't expected to be tapped right away is the pharmaceutical industry.
"The [center's] mission is not to pair up with industry," which often conducts large-scale projects that could "overwhelm an academic facility," Wilson noted. "Right now, we haven't identified any industrial partners … [and] we aren't looking for them. We're not going to be a CRO or any kind of service provider."
Still, "there's some good science being done in industry," he said. "I can't predict the future; for all I know, there will be an industrial scientist who will come to us and will have some shared needs."