back to news Oct. 9, 2018

Wysocki lab making huge advances in protein characterization

Our bodies couldn’t function without proteins, yet scientists still have much to understand about how they’re structured.

That’s because proteins — especially protein complexes made of multiple proteins, or those bound to RNA, DNA or in the cell membrane — are extremely dynamic and interconnected to numerous biological processes, constantly changing, evolving and interacting with other proteins and molecules to meet their goals.

Characterizing protein complex structures, their interactions and how they relate to biological functions is key to identifying, preventing and treating disease, but multiple challenges have prevented this from happening on a large scale.

To close the gap between the number of protein complex structures currently solved and those that are biomedically relevant, a Resource for Native Mass Spectrometry Guided Structural Biology has been formed at Ohio State under the direction of Vicki Wysocki, professor of chemistry and biochemistry, Ohio Eminent Scholar and director of the Campus Chemical Instrument Center.

The Resource is supported by a $6.8 million P41 grant from the National Institutes of Health, which designates the initiative as a national Biomedical Technology Research Resource. These resources are created to develop and disseminate novel, often critical technologies throughout the broader biomedical research community.

The Wysocki Research Group has a proven track record solving challenging, previously unmapped protein complexes through the use of mass spectrometry, an analytical technique used in a wide array of fields that can reveal chemical structures of molecules.

A Thermo Scientfic Exactive plus EMR mass spectrometer, which has been modified to include a quadrupole and SID device, at Ohio State's Campus Chemical Instrument Center.
A mass spectrometer at Ohio State's Campus Chemical Instrument Center. 


“Mass spectrometry has a lot of advantages to study proteins, for example we need only small amounts of material, and we don’t need highly purified material,” Wysocki said. “We want to combine our lab’s methods with existing techniques to create an integrated approach that will provide structural information for most protein complexes.”

Specifically, the Wysocki lab is the first to utilize a mass spectrometry method called surface-induced dissociation, in which protein complexes in the mass spectrometer are smashed at high speed into a surface, yielding valuable structural information while keeping the complex as close to its native state as possible — something other approaches have failed to do.

A scientific instrument designed for surface-induced dissociation, a novel mass spectrometry method being perfected at Ohio State.
A device designed for a novel mass spectrometry technique called surface-induced dissociation, which is being perfected by the Wysocki Research Group.


The new national Resource will build on the lab’s expertise in native mass spectrometry by collaborating with co-principal investigators and Ohio State chemistry and biochemistry faculty members Susan Olesik, Abraham Badu-Tawiah and Steffen Lindert, experts in separation science, ionization and computational chemistry, respectively. Collaborators from Texas A&M University (David Russell) and West Virginia University (Lisa Holland) bring additional knowledge in instrument development and separation science.

“If we can do more kinds of experiments at once that combine as many of our techniques together … we can standardize protein complex structure determination and solve more structures,” said Sophie Harvey, a research associate in Wysocki’s lab and a key partner in the new Resource.

The Resource — housed in the Wysocki lab and the Campus Chemical Instrument Center — will work with investigators across the nation and globe on challenging biomedical projects ranging from viral hemorrhagic fevers and HIV to cataract formation and neurological disorders. 

“A lot of the proteins that we work on are very dynamic; they might exist in different complexes, or they might exist sometimes as two copies of the protein bound together and sometimes four copies. And those can be challenging to study with existing techniques,” Harvey said. “We’ve sought out proteins and projects that are difficult and that we think our technologies can help with.”

Funding for the Resource is renewable for two additional five-year periods, and the team envisions three general phases: technology development, dissemination through beta installations and, finally, widespread commercialization — made possible in part through established vendor partnerships.  

“Our hope is that we can solve more biomedical problems in shorter amounts of time, with less sample and using more streamlined, integrated approaches than currently possible,” Wysocki said.

.@OSU_CBC lab named national Resource for Native Mass Spectrometry Guided Structural Biology. #ASCDaily

 

Ohio State collaborators not mentioned above include Zachary Van Aernum, Florian Busch, Benjamin Jones, Andrew Norris, Erin Panczyk, Samantha Sarni, Justin Seffernick, Arpad Somogyi and Alyssa Stiving.

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