Invitrogen will supply certain researchers from the John S. Dunn Gulf Coast Consortium for Chemical Genomics with siRNA libraries, imaging probes, and real-time qPCR technology to support the consortium’s small-molecule and RNAi-based screens, representatives from both organizations said this week.
The collaboration will have a strong high-content imaging component based on Beckman Coulter’s former IC 100 imaging platform, now supported by Thermo Fisher Scientific’s Cellomics unit. In addition, the partnership may foster additional functional genomics and small-molecule screening collaborations between Invitrogen and GCC-CG’s network of academic labs.
Under the arrangement, Invitrogen will supply scientists from Baylor College of Medicine and the University of Texas Health Science Center — two members of the GCC-CG — with a variety of reagents to conduct large-scale cell-based screens, many of which will incorporate high-content imaging.
These reagents will include unspecified imaging probes from Invitrogen’s Molecular Probes business, “several different libraries” of synthetic siRNA molecules, and the SYBR GreenER real-time qPCR technology.
In a statement, Invitrogen said its work with GCC-CG is a “strategic scientific relationship.” This week, Peter Davies, executive vice president of research at the University of Texas Health Science Center and director of GCC-CG, told CBA News that it was a “broad-based collaborative research interaction” between the Gulf Coast Consortium and several of Invitrogen’s divisions that would help GCC-CG drive its multi-faceted cell-based screening approach.
“We’ve been looking for ways to work and collaborate with private entities such as Invitrogen to [bring] together the different components that are necessary to make this work,” Davies said. “We’ve been working with them in what I would describe as a collaborative arrangement to develop, on the one hand, some of the siRNA screening tools that they have; and on the other hand, looking at some of the things they have that support the imaging-based end of the program.”
Davies said that discussions with Invitrogen started last year when the company helped GCC-CG organize a symposium on image-based screening. This symposium helped familiarize many GCC-CG scientists with various applications of image-based screening, such as functional genomics and small-molecule screens.
“There was a very nice meeting of the minds between myself and others at Invitrogen, and of course [various] members of the GCC-CG, about how to truly understand in a biological context what is happening once cells are challenged — for instance, certain genes are knocked up or down — and how we would need to look at this using a number of different technology platforms,” he said.
Davies said the GCC-CG is “very interested in … marrying image-based screens with other forms of readouts, such as real-time PCR, so that one could capture from the wells, potentially in a multiplexed format, both the images and sufficient amounts of RNA to be able to quantitate transcripts and really do multiplexed multiple readouts from individual wells and samples.”
These types of screens contribute both to basic biomedical research and small-molecule drug discovery research, he added.
“It’s really actually part of the evolution that we think is going on within this field,” Davies said. “When we had launched the consortium two or three years ago, our focus was largely on small-molecule-based screening strategies. But we’ve come to appreciate that … the two go hand in hand; that with siRNA-based screens, there is the opportunity to potentially define targets, and then come back with more targeted small-molecule screens, to focus in on the targets of interest for a particular endpoint.”
The GCC-CG’s screening efforts will have a large high-content imaging component, and will primarily use the IC 100 imaging cytometer, formerly sold by Beckman Coulter. Though the platform is no longer commercially available, Cellomics services and supports the platform with a small group of Beckman employees.
The GCC-CG, and in particular the Baylor College of Medicine, was one of the early adopters of the IC 100 instrument, dating back to when it was called the EIDAQ 100 and sold by Q3DM, which was subsequently acquired by Beckman. In particular, Mike Mancini, an assistant professor of molecular and cellular biology and director of the Integrated Microscopy Core at Baylor, invested early on in a pair of IC 100's to support research on interrogating transcription function in live cells and for some GCC-CG screening activities.
And, despite the fact that the IC 100 is no longer commercially available, GCC-CG will continue to base its high-content imaging work around it.
“The focus of the consortium — and we’re very much configured to support the needs of our investigators — [is] to be able to support a variety of research programs,” Davies said. “Some of them, and particularly in the siRNA area, are built around our high-throughput imaging capability. There, the focus of the consortium is on the Beckman instrumentation. We have several of the IC 100 scopes; we like them, we’re frankly impressed with their capabilities, and are pleased with the way we’re using them.”
“This is something that I hope and I think is starting to get some traction, and we definitely look forward to an increase in the amount of academic high-throughput technologies because I think we’re well-positioned to help there.”
Davies added that GCC-CG will also employ more “conventional,” non-image-based readout technologies, such as multi-mode plate readers, as well as instrumentation for conducting high-throughput real-time PCR for gathering quantitative information on transcripts.
“Merging that technology in terms of PCR-based screens, particularly in a 384-well format, for some of our investigators, is going to be attractive, particularly for those who are looking at complex biological endpoints, such as cell differentiation endpoints,” Davies said.
A Developing Market?
It is unclear whether GCC-CG is paying Invitrogen for access to the reagents. Lewis Vann, business development manager for Invitrogen’s Consortium Program, declined to comment on whether partnerships like this with academic or non-profit institutes constitute a potential ongoing revenue source. However, he noted that Invitrogen, like many other biotech tool providers, is eyeing the academic research and screening markets with interest.
“We think it has large, untapped potential because … the approach of the academic process of screening is to be more hypothesis-driven,” Vann said. “So rather than throwing a chemical library at something and looking at the outcome, it’s actually understanding the gene regulation that’s involved and doing some informed, targeted profiling.
“This is something that I hope and I think is starting to get some traction, and we definitely look forward to an increase in the amount of academic high-throughput technologies because I think we’re well-positioned to help there,” Vann added.
Another prime example of this trend is the National Institutes of Health’s Molecular Libraries Screening Center Network, which comprises screening centers at several US universities. The MLSCN has thus far fostered multiple collaborations with industry, and while many of those relationships may not become cash cows for the involved companies, they have helped promote their technologies through the publication of validated data.
The GCC-CG comprises four additional member universities – Rice University, University of Houston, University of Texas MD Anderson Cancer Center, and University of Texas Medical Branch at Galveston – besides UT-Houston and Baylor College of Medicine.
Although GCC-CG is not part of the MLSCN, it seems to be developing a comparable multi-location screening network — or, as Davies called it, a “hub-and-spoke arrangement.” It is here that the GCC-CG has worked closely with Beckman Coulter beyond the area of HCS to develop a common automation infrastructure, and as such may similarly prove to be rife with opportunity for further collaborations with Invitrogen or other industrial partners.
“We’ve had a lot of support and worked closely with Beckman Coulter in terms of our robotics and automation, and in building our GCC network, where the central screening laboratory is equipped for the library and compound collection screens,” Davies said. “Then our participating individual institutions are putting in place satellite laboratories where the assay-development work takes place. We’re working hard to make sure the platforms are the same so that assays developed in the satellite laboratories can move as efficiently as possible to the central screening platform.”