Feature
Making the Most of Disorder
June 21, 2007
Ya-Yue Van describes how she's building a business on the science of protein disorder
Ya-Yue Van, president of Molecular Kinetics, Inc. is taking the research from her husband, IU bioinformatics center director Keith Dunker, to the marketplace.
Ya-Yue Van calls her company a "one-stop shop for disordered proteins."
To the uninitiated, it may sound like a home for unruly cousins of the critical molecules that control the activities of every living cell.
But her Indianapolis company, Molecular Kinetics, could someday be the origin of a powerful drug to cripple cancer cells or reverse the ravages of Alzheimer's disease.
It's hard to predict, because, as Van says, the field of disordered proteins "is like virgin territory. Any seeds you plant there — let's see what sprouts!"
Van and her tiny company are hoping to grow something from science and software developed by her husband, Keith Dunker, director of the Indiana University School of Medicine's Center for Computational Biology and Bioinformatics, and one of the founders of the field of protein disorder.
The standard thinking about proteins has been this: The function of a protein depends on its structure. To do what it does, a protein must fold into a particular shape. But Dunker and a growing number of scientists are studying other portions of proteins that don't fold into specific structures — regions they call "disordered."
Dunker's research has shown that these disordered regions play important roles in cell signaling, which makes them important in the study of variety of diseases, including Alzheimer disease, Parkinson disease and cancer.
In fact, Van says, the research indicates that of proteins known to be associated with diseases, eight percent of those involved with signaling are "ordered," but 21 percent are "disordered." Currently, she said, most research at pharmaceutical companies focuses only on the ordered proteins. As a result, many potential targets "are basically being thrown away."
As Dunker developed his research, Van said, "We talked about the fact that he had invented the basic science, but nobody knew what to do with it commercially. So we wanted to see if we could turn it into applications that people can use for the good of society."
So Van and her company licensed the software, known as PONDR, that had been developed as part of the research from Washington State University, where Dunker conducted his initial work in the field.
In 2003, however, Dunker was recruited as part of the Indiana Genomics Initiative to head the new bioinformatics center. As a result, Molecular Kinetics moved to Indiana along with Dunker and Van.
Subsequently, Vladimir Uversky, another pioneer in this protein field, was recruited from the University of California Santa Cruz to become a senior research professor of biochemistry and molecular biology at the School of Medicine and director of research at Molecular Kinetics.
Since then, Van and her tiny Molecular Kinetics team have been developing their science with the assistance of seven Small Business Innovation Research Awards and matching grants from the Indiana 21st Century Research and Technology Fund.
The company has developed both the PONDR software and created databases of information about proteins known to be associated with human disease, licensing them to more than 2,000 commercial and academic users around the world.
But the protein research is leading in unexpected directions. In the near term, for example, the company is developing a laboratory tool called AquoProt for dissolving proteins.
"Protein insolubility is a big problem for all protein chemists — to work with them they have dissolve them in water," Van said. AquaProt promises to be a dramatic improvement over current products if the company can get the funding it needs for development.
"We have the proof of principle. If we had an infusion of money now, about $2 million, we could get it to market in less than two years."
The result, she would be a $10 million to $16 million business.
Then there's drug discovery. Molecular Kinetics has developed databases containing information on proteins associated with cancer, cardiovascular disease, diabetes, neurodegenerative disorders and auto-immune disease. That information could be used, in a process called "rational drug discovery," to develop molecules that would block interactions that lead to disease, especially among the "disordered" proteins in which Molecular Kinetics specializes.
Drug discovery will be a long-term process, however, Van said: "10 [to] 15 years, easy."
Molecular Kinetics started out as an informatics company, she said. "We had no idea this was going to lead to drug discovery. It turns out, that's what grew out."
