The University of Pittsburgh and Carnegie Mellon University said this week that they will use a five-year, $13.3 million grant from the National Institutes of Health to establish a National Technology Center for Networks and Pathways.
The center, to be housed on CMU's campus, will focus on "developing fluorescent probes and imaging technologies to investigate regulatory pathways and networks in real time in living cells," according to a statement from the universities.
It also is expected to spawn multiple industry collaborations, partly due to the pharma-scale screening work being conducted as part of UPitt's Molecular Libraries Screening Centers Network endeavor, and partly because several of the new center's lead investigators have close ties to industry.
"There is a close industry cross-over here, because building these systems and these dye technologies in isolation without close collaboration with industry would be rather foolish," said Simon Watkins, co-director of the new center and professor of cell biology, physiology, and immunology at UPitt. "We can't pretend to have the wherewithal to build cameras and many of the other technologies we need."
"There is a close industry cross-over here, because building these systems and these dye technologies in isolation without close collaboration with industry would be rather foolish."
The NTCNP is one of five similar centers funded through the National Center for Research Resources in recent years. According to Douglas Sheeley, program director for the NCRR, the NIH made two awards for such centers in 2004: $18.3 million to the Burnham Institute for a "Center on Proteolytic Pathways;" and $17 million to Johns Hopkins University for "Networks and Pathways of Lysine Modification."
Sheeley said that the NCRR, which is administering the NTCNP grants, received a second round of applications from interested institutions in 2005, and in the fall of that year made awards for three additional centers: $12.5 million to Rockefeller University for "New Tools for Exploring the Dynamic Interactome;" $12.3 million to the University of Connecticut School of Dentistry and Medicine for "Polarity in Networks and Pathways;" and $13.3 million to UPitt/CMU, for "Fluorescent Probes and Imaging for Networks and Pathways." All of the awards are for five years.
"We won't be funding any more centers," Sheeley told CBA News this week. "That's the end of the announcements, and we won't renew the call for applications."
The status of UPitt and CMU as an NTCNP is significant because UPitt was also one of nine institutes in 2005 to have been named a member of the Molecular Libraries and Screening Centers Network established under the NIH's Roadmap for Biomedical Research (see CBA News, 6/20/2005).
The Burnham Institute also has this distinction, but the difference is that the principal investigator on the UPitt MLSCN grant, John Lazo, is also on the NTCNP grant. In fact, several researchers can be found on both grants, including Watkins and CMU professor Alan Waggoner, who is principal investigator on the NTCNP grant and co-director along with Watkins. The PI for the Burnham Institute's NTCNP is not involved with the MLSCN project at Burnham.
"You can find commonalities in different Roadmap programs because they tend to be inter-disciplinary programs," Sheeley said. "So while they don't really overlap, they bump up against one another, and there are these edges where I think there will be opportunities for folks to work together.
"John [Lazo] and Alan [Waggoner] and several other folks are long-time collaborators, and they certainly are going to take advantage of opportunities to help each other, and to leverage the investments," Sheeley added. "That's a good thing. Where these programs do happen to have some adjacencies, because of funding at the same institutions, we're really happy when they can help each other out."
Or, as Watkins put it, "essentially the NIH gets more bang for the buck. There is not overlap, but they'll facilitate each other. You can't have a grant that has overlap. I'm on both grants, and we will be developing assays and products in the Pathways grant that will be used in the MLSCN. So they're mutually supportive."
The NTCNP at UPitt/CMU is also unique in that it arguably has the largest live-cell imaging component to its research of any of its contemporaries. Watkins is the director of UPitt's Center for Biologic Imaging, which houses about 25 microscopes ranging from confocal laser scanning to epifluorescence to electron. Meanwhile, Lazo directs UPitt's Fiske Drug Discovery Laboratory, which regularly runs industrial-scale drug screens, many of which involve high-content automated imaging.
And, according to Watkins, there will likely be the need to acquire additional imaging-related hardware to support the NTCNP work. It remains to be seen whether this means fully automated imaging systems or off-the-shelf components such as cameras, basic microscopes, and filters. Watkins, for one, is heavily involved in building imaging systems from scratch, while many of the other researchers involved have a great deal of comfort and expertise with automated imaging systems.
"We use a lot of off-the-shelf products," Watkins said. "We have hardware budgets, but a lot of my hardware budget is machine time and electronic shop time to build specialized pieces for me. Certainly on top of that are defined hardware acquisitions."
Many of the investigators on the NTCNP grant also have close industry ties. For instance, Watkins said he sits on the scientific boards of Molecular Devices and Photometrics, a division of scientific camera maker Roper Scientific. Waggoner is the co-founder of three biotechnology companies, including Cellomics and Cellumen, and was or is a member of those companies' scientific advisory boards. He also worked for Amersham Biosciences (now GE Healthcare) for a brief period between academic stints.
Watkins said that an example of how he'll be working with industry is to develop new and more sensitive cameras that are capable of imaging the types of dyes and sensors being developed by UPitt and CMU.
"We're working with another [academic] group as a part of this, peripherally, on long-wavelength dyes," Watkins said. "To image these, you need long-wavelength cameras, and there are very few out there at the moment that have a high QE in the near-IR — right now there is only one or two that has any sensitivity in the 1,000-nm range.
"I'll be working directly with industry to encourage them to build me cameras that will work that way, because I'm not building a camera," Watkins said. "So that's the kind of interactions I have with industry, in that we come up with a specific need."
One of the first projects to come out of the new center will be the development of an improved biosensor for kinases, Watkins said, which will eventually be used in Lazo's HCS work.
"Until now, no one has created fluorescent probes to visualize kinase and phosphatase reactions," CMUs Waggoner said. "But there are many hundreds of these reactions within cells, and they are critical to driving pathways involved in disorders like cancer, diabetes, stroke, and infection."
— Ben Butkus ([email protected])