After completing negotiations to hammer out intellectual property issues, MitoKor said last week that it had signed formal agreements with the Buck Institute for Age Research and the University of Oregon to collaborate on a comprehensive study of the human mitochondrial proteome.
The three parties have agreed to share their respective expertise in protein separations, mass spectrometry, and cell biology to identify the 1,500 to 2,000 proteins believed to inhabit human mitochondria. San Diego-based MitoKor hopes to use the resulting data to identify potential drug targets for neurodegenerative diseases such as Alzheimer’s, type II diabetes, and age-related diseases such as osteoarthritis, said Thomas Sanders, MitoKor’s vice president for business development.
Sanders declined to disclose the exact nature of the intellectual property arrangements between the three parties, but said that the company has the right of first refusal for any discoveries resulting from the research. “Eventually we’ll make the database [publicly] available when appropriate,” he said, although he wouldn’t predict when that would occur.
MitoKor first began working with Buck Institute researcher Brad Gibson several years ago on a preliminary basis to develop the company’s mass spectrometry capabilities, and on research involving oxidative stress, Gibson said. The recently signed agreement marks the beginning of a specific project to detail all the mitochondrial proteins.
“We were working off the cuff for the last six to eight months [on the mitochondrial proteome],” Gibson said. “We’re just now starting to move more quickly and aggressively in the area.”
In return for research funding, Gibson will help MitoKor analyze the mitochondrial proteins using his Applied Biosystems MALDI-TOF and Q-TOF instruments, he said. Gibson also helped set up MitoKor’s mass spectrometry lab in San Diego, where the company makes use of Thermo Finnigan ion trap spectrometers for peptide sequencing.
MitoKor has also licensed both gel and 2D chromatographic separations technology from the University of Oregon, where biologist Roderick Capaldi initially developed the techniques. Capaldi is supplying MitoKor with the mitochondrial samples, as well as contributing his expertise in subfractionation and the design of antibodies specific to mitochondrial proteins.
Gibson said the dynamic range and variety of insoluble proteins in the mitochondrial proteome makes accessing non-gel separation techniques necessary. “We need new chromatographic strategies that don’t require 2D gels, because [2D gels] don’t have the dynamic range or the ability [to handle] membrane-associated proteins,” he said.
As the project progresses, Gibson said the team will most likely seek out new technologies, such as those being developed in the labs of Ruedi Aebersold of the Institute for Systems Biology and Brian Chait at Rockefeller University, that will help the researchers delve more deeply into the mitochondrial proteome.
“I don’t think we have everything in place right now, we’ll make our way and get about 30 to 40 percent into it over the next year, and look around for new technologies,” he said. “Proteomics is such a fast-evolving field that we just don’t know which technologies will be developed.”
In a previously announced agreement, MitoKor is collaborating with the University of California, San Diego, to develop an annotated database of mitochondrial proteins. Sanders said the company is helping to fund the database development work at UCSD and the San Diego Supercomputing Center by matching a California state grant designed to encourage industry-academic partnerships.
Simon Melov, another researcher at the Novato, Calif.-based Buck Institute, is collaborating with Proteome Systems researcher Mary Lopez on a project to study mitochondrial proteins in mice. Gibson said the two projects do not explicitly overlap.
— JSM