Persistence to isolate elusive protein leads to publication and scholarship

08/20/13 Portland, Ore.

Cristina Butterfield, OHSU graduate studentCristina Butterfield is a persistent science student. How else would you describe someone who would take on a research project where four previous students had failed, make a new discovery, turn it into a published research paper, and receive a Vertex Scholarship?

Butterfield is a graduate student in the Division of Environmental and Biomolecular Systems at OHSU’s Institute of Environmental Health. Working with her advisor Dr. Brad Tebo, Butterfield’s research focuses on the isolation of a protein that oxidizes manganese and makes manganese oxide minerals.

For several years, she attempted to isolate an elusive protein and ultimately discovered that the functional protein required the organization of three proteins, an unprecedented trait to this family of proteins. Her research findings were published in the Proceedings of the National Academy of Sciences (PNAS) on July 1, 2013.

"Nobody has ever studied a manganese oxidizing protein before because it has never been available in enough abundance," Butterfield said. “I am the first to isolate it and describe its ability to bind copper and facilitate Mn oxidation.”

Her major findings demonstrate that bacterial manganese (Mn) oxidation from soluble Mn(II) to insoluble Mn(IV) oxides is a two step reaction catalyzed by a multicopper oxidase (MCO)-containing complex. She and her co-authors posit that their protein transfers electrons from Mn to protein-bound copper (Cu) and finally to oxygen (O2), forming MnO2 oxide minerals and water. These minerals have similar chemical signatures as those found on the surface of Mn oxidizing bacteria, supporting the argument that their protein is the driving force for Mn mineralization in the environment.

“Cristina’s breakthrough in purifying the active manganese oxidase will enable scientists to uncover its mechanism, potentially applying it in new technologies for bioenergy and pollution remediation, and generally broadening the understanding of manganese mineral formation and the bioinorganic capabilities of multicopper oxidases,” Tebo said.

With her first lead author manuscript accepted, she has learned that a handful of collaborators are eager to participate in studies with her purified protein. She has also filed a provisional patent application with OHSU’s Technology Transfer and Business Development.

“I feel privileged to work with established scientists, learn new techniques, and become a bona fide biochemist,” Butterfield said. “The chemical nature of the challenges I have now are easily overcome compared to the inherent unpredictability of biological protein production.”

If that research achievement wasn’t enough, Butterfield’s determined attitude has recently garnered her a Vertex Scholarship. The OHSU-Vertex Educational Partnership Program offers $35,000 scholarships funded by Vertex Pharmaceuticals, a biotechnology company based in Cambridge, Mass. The award will fund Butterfield’s stipend and fees for one year.

"I can say that my persistence paid off in the end and I am hopeful that the trend will continue," Butterfield said. “The scholarship will help advance my research findings and hopefully provide me with a prolific final year in graduate school.”


OHSU Institute of Environmental Health believes preventative medicine starts with a healthy environment. There is overwhelming evidence that human activities and the global climate are affecting environmental health and sustainability. Increasingly, these consequences are causing serious implications for human health. IEH seeks to develop scientific understanding in environmental and biomolecular systems that  elucidates environmental processes and their links to human health.