Mass spectrometry has become one of the must-have tools of modern biology. The technology brings a new level of precision to challenges such as developing effective drugs, diagnosing diseases early and monitoring the progress of treatments.
The Morgridge Institute for Research, as part of its Metabolism Initiative, is working with a University of Wisconsin–Madison team to greatly expand the scope of “mass spec” applications on campus. A new resource housed in the UW–Madison Biotechnology Center brings together a multi-million dollar investment in mass spectrometry tools from multiple sources to form a central repository to tackle large-scale investigations.
Joshua Coon, a UW–Madison professor of chemistry and biomolecular chemistry and renowned innovator of mass spec technology, will lead the new initiative. Jason Russell was hired by the Morgridge Institute in October to lead the daily management of the lab.
“We are attempting to develop the capability to empower any kind of metabolism systems research that scientists here could imagine doing,” says Coon. “We want to follow a collaborative model that provides users with the expertise to help interpret the data and bring the results into their experiments.”
Mass spectrometry is a method of determining the precise chemical identity of a substance. It is able to measure the molecular mass of compounds in a sample and quantify their abundance, which is often the first step in determining the role it plays in biological function or disease.
“You can put in a tremendously complex mixture of chemicals, and use mass spectrometry to pull out the precise chemical mass of hundreds of compounds, and also determine the amounts of each compound in a sample,” Coon says.
The potential of that type of precision is enormous. Coon cites a current project with the Wisconsin Registry for Alzheimer’s Prevention, a multi-generation study with more the 1,500 subjects that looks for risk factors of the disease. Coon’s team has analyzed more than 300 plasma samples from people who have already shown signs of dementia and from those who have shown no symptoms. By identifying what groups of molecules express differently across different cohorts, they hope to identify Alzheimer’s risk factors even before clinical symptoms arise.
“Mass spectrometry can tell you what’s going wrong early enough to offer up targets for therapy and intervention,” he says.
Coon says the team hopes to develop a formal plan this spring for how the lab will operate. The team researched similar resources at a number of research universities and found that the best models are built on collaborative science, rather than a traditional core service. The goal will be to get involved early enough to influence the design of research projects to maximize the value of mass spectrometry to the ultimate questions scientists are after.
After a few years of operation, Coon says the goal would be to support the resource through mass spectrometry projects written directly into new research grant proposals.
Russell says UW–Madison researchers are only scratching the surface of the technology’s potential. In his first two weeks after taking on the associate director role, researchers from departments across campus have already contacted him with big ideas on collaborating.
“You can see the excitement in their eyes because they have a hypothesis and they think they know what’s happening,” says Russell. “They just don’t have the tools to help mine the information. That’s where we come in.”
Investing in mass spec capabilities is one of the top priorities of the Morgridge Metabolism Initiative, says Morgridge CEO Brad Schwartz, since it is one of the foundational tools for measuring metabolic chemistry.
“We’re pleased to be able to move quickly on this investment and put a resource in place that will be used by a wide array of research areas on campus,” Schwartz says.
The lab will bring together mass spectrometers from three different places: The Coon Research Group; Dave Pagliarini, director of the new Morgridge Metabolism Initiative; and the Great Lakes Bioenergy Research Center. The Morgridge Institute and the Department of Biochemistry supplemented the fleet this fall with funding to purchase three new mass spectrometers.
“We see this as helping the science progress at a much faster pace, by removing the limiting factor of data interpretation,” Russell says. “We will have people able to interpret data and relate it on a level that allows researchers to map it back to their biology.”
Russell, who earned his PhD from the Coon lab in 2012, came to Morgridge from Agilent Technologies in Madison, where he saw firsthand the burgeoning demand for mass spec and the spike in activity around metabolism.
While the lab will formally open in early 2016, Russell is interested in talking to UW–Madison scientists about potential collaborations. If you have ideas, contact Russell at jrussell@morgridge.org.