Taking advantage of the Canadian government’s multihundred million dollar program to foster the country’s biotech research capabilities, Affinium Pharmaceuticals, née Integrative Proteomics, said last week that it had received $7 million from Genome Canada and the Ontario Genomics Institute to study viral proteins.
The project, which was approved for funding by a committee of scientific and financial advisors assembled by Genome Canada, will involve Affinium as well as several of the company’s academic collaborators with expertise in virology, said Molly Schmid, Affinium’s vice president for antibacterial pharmaceuticals and alliances. Together, the researchers hope to systematically express, identify interactions between, and determine the structures of proteins isolated from pathogenic viruses.
To augment the company’s proteomics technologies, Affinium has signed on three academic virologists, Grant McFadden, an expert in poxvirus at the John P. Robarts Research Institute in London, Ont., Lori Frappier, an expert in Epstein-Barr virus at the University of Toronto, and James Smiley, an expert in herpes simplex virus at the University of Alberta, to help guide the company in its exploration of the viral proteomes.
Schmid declined to disclose the specific viruses the company plans to investigate, but said that the goal is to study all of the key viral pathogens, from the very simple, such as hepatitis C virus, to the very complex, such as herpes simplex. “It’s a project to explore viral proteins and the host proteins that interact with [them] to learn more about the cell biology of viral infection, [and] from a more applied point of view to identify more information about the viral proteins themselves for the purpose of using them as antiviral targets for small molecule drugs,” Schmid said.
Because the Canadian government is providing the funds for the project, Schmid said Affinium is obliged to make its data publicly available. “The government is really seeking to foster science as a broad statement; they’re not looking to subsidize companies, so we will make our information available to the academics,” she said, adding that “obviously we are a company so we will protect our commercial interests.”
An independent scientific steering committee that includes representatives from Affinium and Genome Canada will manage the financial and scientific interactions between the industrial and academic partners, Schmid said. Selecting the viruses to study will be based on the severity of the disease, its prevalence in the human population, and the prospects for developing an effective vaccine in the near future, she added.
Affinium plans to collect its data on the viral proteins’ function and structure by first cloning and expressing the proteins using genomic information, and then applying its platform of protein-protein interaction and structure determination technologies.
To study protein-protein interactions, Affinium has developed techniques for labeling purified recombinant proteins, allowing the purified proteins to associate with whole cell extracts, and then isolating the resulting protein complexes via microaffinity chromatography. After digesting the protein complexes, the company attempts to identify the constituents by MALDI-TOF or electrospray TOF mass spectrometry, using the Bruker Daltonics instruments Affinium has on-site. If MS/MS capabilities are required to accurately identify the proteins, Affinium researchers have access to electrospray ionization tandem mass spectrometers at the Ontario Genomics Institute’s core proteomics facility in Toronto.
Affinium will acquire structural information on the viral proteins with the help of the x-ray crystallography and NMR instrumentation it acquired from Bruker AXS and Bruker BioSpin, respectively, in a March 2001 deal in which the three Bruker companies made an undisclosed investment in Affinium in return for an exclusive vendor partnership. Affinium can also co-crystallize and determine the structure of protein complexes identified via affinity chromatography, said Affinium CEO John Mendlein, with an average resolution of 2.2 Å. Mendlein claimed that the company can crystallize and determine the structure of proteins ranging in size from 10 kDa to 400 kDa in as little as four weeks.
Schmid added that Affinium will most likely determine the structures of all the viral proteins it expresses, because the company’s robotics allow the crystallization and structure determination to occur in a reasonable frame of time. Now the difficult decisions involve which protein to pursue as a drug target, as opposed to which protein’s structure is worth determining, she said. “It''s a much more interesting and difficult question [as to] which of these we are going to choose to go after for drug targets,” she added.