Located in the Department of Chemistry and Chemical Biology, the centralized facility will produce proteins for cancer-related research throughout Cornell's Ithaca campus as well as at the Weill Medical College of Cornell and its Tri-Institutional Collaboration partners (Rockefeller University and Memorial Sloan-Kettering Cancer Center) in New York City.
At first the facility will produce milligram quantities of naturally occurring proteins for structural analysis with X-ray crystallography and nuclear magnetic resonance (NMR), using bacterial (E. coli ) and insect cell systems. Subsequently, as rational design identifies molecular targets to treat disease, the facility can scale up to produce larger quantities of proteins for clinical trials in the Comparative Cancer Program of the College of Veterinary Medicine and at other cancer centers.
Another goal of the new Cornell facility is to move beyond bacterial and insect cell-based production systems to the much more difficult -- but potentially useful -- process with mammalian cells, according to Danny Manor, assistant professor of nutritional sciences and director of the laboratory.
"Biomedical research benefits tremendously from being able to understand the three-dimensional structures of relevant proteins," Manor explains. "Such molecular-level pictures can open the door for educated design of intervention strategies by modifying the protein's biological activity."
But a bottleneck in structural determination of proteins often is the limited supply of highly purified proteins, Manor notes. "A centralized facility, where the necessary resources (equipment, personnel and know-how) are available, achieves three objectives: access for researchers who are not able to prepare such proteins on their own, reducing the cost associated with large-sale protein production, and expert help and training for interested investigators."
One cancer researcher who understands the difficulty of producing purified proteins and welcomes the new facility is Richard Cerione, a professor in the Departments of Molecular Medicine and Chemistry and Chemical Biology. His studies of molecular "switches" and other signaling components during malignant transformation of cells are aimed at eventually developing intervention strategies. But first he must determine the structure of numerous proteins functioning in complex, and that requires quantities of purified proteins that have been made, with considerable difficulty, in his labs.
"Our ideal goal, if we know the structure of a molecule we think is playing a role in cancer, is to make a small molecule in chemistry that can affect the protein's activity, then test the small molecule in clinical trials," Cerione said. "The first step is to be in a position to obtain molecular information about these important proteins. The advantage of a specialized, centralized facility is to bring together a lot of diverse groups on campus and in New York to expedite getting detailed information about cancer-relevant proteins."
Regarding clinical trials of treatments that are developed from basic-science studies, Rodney L. Page, director of the Comparative Cancer Program and professor of clinical sciences, says, "It could be quite a while before that happens. But the hope is that by identifying a protein and being able to determine the structure, we can modify it to make it work better or inhibit its function. Then we might be able to develop a research program and test in various systems, from in vitro systems up to the animal models."
The new facility has been producing proteins from bacterial systems for several months, and capabilities for insect-cell production are about to be added, Manor reports, "but structural determination of proteins produced in mammalian cells is not something that is done yet, anywhere, so that is a goal to look forward to."