Eric Ross, associate professor of biochemistry and molecular biology at Colorado State University in Fort Collins, was awarded an MDA research grant totaling $363,000 over a period of three years to study proteins whose aggregation causes neurodegeneration.

Neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), are characterized by the formation of protein clumps, or aggregates, in or around muscle-controlling nerve cells called motor neurons. Aggregates also are seen in the muscle disease inclusion-body myositis (IBM). These aggregates are believed to indicate an ongoing toxic process within the cell and may be toxic themselves.

“Interestingly, similar protein aggregation can be seen even in simple single-cell organisms such as yeast,” says Ross. Some aggregates can harm not only the cell in which they form, but also neighboring cells by spreading to them and inducing aggregation. Such proteins are called prion-like for their resemblance to proteins found in prion diseases like bovine spongiform encephalopathy (mad cow disease).

Yeast makes a powerful model system in which to study the spread of prion-like proteins, Ross says, because it grows rapidly and its genes can be easily manipulated. “Based on studies in yeast, our lab has developed methods to identify new disease-associated proteins in other organisms. Remarkably, in just the past few years, various labs have linked mutations in six of these proteins to certain inclusion-body myopathies and some forms of ALS.”

Ross will be examining how the sequence of amino acids in these proteins affects aggregation and toxicity, and how disease-associated mutations change the physical properties of the proteins.

“These studies will provide insight into the causes of these diseases, facilitate the identification of potential drug targets for therapeutic intervention, and improve our ability to identify other disease-associated prion-like proteins,” he says.

Funding for this MDA grant began Feb. 1, 2013.