This article has been updated from a previous version to include a comment from an Odyssey Thera official regarding the company's technology.
The National Institutes of Health's Chemical Genomics Center will use cell lines and reporter gene technology from Invitrogen to identify activators or inhibitors of disease pathways such as the MAP kinase pathway, Jak-STAT pathway, and hypoxia response, Invitrogen said this week.
Though the agreement lacks any direct financial benefit for Invitrogen, which is giving NCGC the tools for free, it could spur revenue-generating collaborations down the road involving other Invitrogen assay technologies, such as its RNAi reagents and protein microarrays.
The company said it also hopes the deal will help "train the next generation of screeners to use these technologies" and therefore tap new revenue sources in the future.
For the NCGC, the collaboration, which is part of its high-throughput chemical genomics-based effort to profile its collection of small molecules in cells, adds to its growing stable of cell-based assay technologies borrowed from industry in support of the Molecular Libraries Roadmap initiative.
With these tools, the agency aims to conduct industrial-scale screens of a small-molecule repository to extend the findings of the Human Genome Project into a similarly comprehensive map of drug targets, protein interactions, and disease phenotypes, and deposit the data into PubChem, NCGC said. (The latest data deposited into PubChem from collaborative screening campaigns can be seen here.)
"Chemical genetics approaches are more like fishing expeditions — sometimes you come back with a sunfish, sometimes you come back with a tuna."
Specific terms of the collaboration call for Invitrogen to supply NCGC five of its CellSensor cell lines, which use GeneBLAzer beta-lactamase reporter gene technology. Invitrogen describes CellSensor as optimized, stable cell lines that can measure the intracellular effects of growth factors or drug candidates on signal transduction pathways, or interrogate individual steps within particular signal transduction pathways using the ratiometric beta-lactamase readout.
The NCGC will then screen the cell lines — most likely in parallel — against its library of small molecules.
"An area of investigation by the NCGC involves the broad profiling of large chemical libraries against an array of cellular assays," Jim Inglese, director of biomolecular screening and profiling at the National Institutes of Health's Chemical Genomics Center, wrote to CBA News in an email. "The assays from Invitrogen are included, among others, in this ongoing study — the idea being that the resultant pharmacology collected across a host of cellular model systems will provide general insights aiding the understanding of the molecular basis of compound activity in complex cellular settings."
Other cell-based assay technologies NCGC has recently either adopted or evaluated for adoption include Italian biotech Axxam's cell lines with glow luminescence reporter technology (see CBA News, 1/13/2006); DiscoverX's PathHunter brand of cell-based assays featuring enzyme fragmentation complementation technology (CBA News, 11/7/2005); and Odyssey Thera's cell lines featuring protein-fragment complementation technology (CBA News, 8/29/2005).
John Printen, R&D director of Invitrogen's Drug Discovery Solutions business, told CBA News that each of the cell-based assay technologies has a particular place in the NCGC project.
"I think it depends on what [scientific] question you're asking," Printen said. "I know they have some cell lines from Odyssey, and that's looking at very specific protein-protein interactions. With the CellSensors, you're interrogating an entire signal transduction pathway, so you're looking at multiple points of intervention, essentially."
According to John Westwick, Odyssey Thera’s president and CEO, Odyssey’s technology is also conducive to investigating entire signaling pathways. “Odyssey is probing entire pathways and networks in living cells, not simply a specific protein interaction,” Westwick said. “We have done compound screening with literally hundreds of our assays, and the vast majority of hits turn out to be regulating targets within the signaling pathway or network of interest, but rarely on the proteins comprising the assay.”
Invitrogen will be providing the cell lines to NCGC without charge, and Invitrogen researchers will not be actively participating in the screening efforts. However, Printen said, the possibility exists for them to do so in the future.
"In the first instance, we're only providing the cell lines and reporters, but we're leaving it open," Printen said. "If interesting compounds come out, we would look to then use some of the RNAi technologies in house at [our] Madison, [Wisc., facility] to knock down particular genes along the pathway that we think are involved, and see if we can phenocopy the compound effects.
"Our goal is to train the next generation of screeners to use these technologies that were developed specifically for high-throughput screening," Printen said. "We find that people in the academic community are just adapting what they are currently using, and those may not be getting them the right answers.
"As high-throughput screening becomes more commonly accepted in the academic community, we want postdocs and graduate students to be using beta-lactamase and the other Invitrogen technologies," he added. "I think that's where we'll see the financial benefits."
Still, there is no guarantee that the NCGC will collaborate with Invitrogen in the future — NCGC's Inglese declined to comment on the potential — but Printen believes that at the very least, NCGC's screening work will serve to "demonstrate the utility of the technology and how powerful it can be" to the general research community.
Printen added that a future collaboration is "something I would like to see happen. Going into it, we just didn't know what we'd be turning out, because chemical genetics approaches are more like fishing expeditions — sometimes you come back with a sunfish, sometimes you come back with a tuna."
— Ben Butkus ([email protected])