A Chain for the Better

Twenty amino acids, driven by the genetic code, form thousands of protein chains that fold into just the right conformation to maintain cell function — until something goes wrong.

It’s part of the “protein folding problem,” and it’s one of the most difficult puzzles scientists have ever faced. To maintain human life, amino acids are continually used to form protein chains, which then fold into precise three-dimensional conformations in order to function properly. Sometimes, however, the protein chains misfold, for reasons that remain a mystery, and the mutant proteins malfunction — causing chronic disease.

The Mystery of Misfolded Proteins
“Understanding the amino acid sequence of how a protein folds into its final conformation remains one of the greatest unsolved problems in biochemistry,” says Wilfredo Colón, Rensselaer associate professor of chemistry, and 2000 winner of the prestigious Presidential Early Career Award for Scientists and Engineers.

Fortunately, for humankind, scientists like Colón are on the case. He is researching the toxic effects associated with the misfolding of the protein Superoxide dismutase (SOD1), which causes 20 percent of the cases of Familial Amyotrophic Lateral Sclerosis or FALS – or Lou Gehrig’s disease. In addition, his fundamental research recently earned him a $1,000,000, four-year grant from the National Institutes of Health to study how mutations in SOD1 may lead to this devastating disease.

Breaking the Chain Reaction
Lou Gehrig’s Disease (FALS) is a deadly neurodegenerative disorder nicknamed after the legendary baseball player who contracted it. FALS is uniquely interesting and challenging because some SOD1 mutations lead to an aggressive form of the disease, killing patients within a few years after it appears. Another SOD1 mutation causes a milder form of the disease that allows patients to live nearly two decades after the first symptoms. Colón’s research team is working to discover what causes one mutant form of SOD1 to be more deadly than the other. Is it a protein-folding problem or some associated defect? Regardless, the ultimate goal is to understand the toxic effects that result from the SOD1 mutations and devise drugs to counteract them.

Colón’s research also holds promise for Alzheimer’s disease, the most prominent of all neurodegenerative disorders, since it, too, is associated with the misfolding and self-assembly of proteins. In fact, there are 20 known diseases linked to the degenerative effects of misfolded proteins, all of which could be helped by Colón’s research.

Why is Rensselaer Trying to Find Good Proteins Gone Bad?
Misfolded proteins are linked to a variety of illnesses associated with age. Finding answers to age-related diseases goes to the heart of improving the quality of life for all mankind, with innovations that will help people around the globe live longer, healthier lives. At its most fundamental level, this research represents the very mission of Rensselaer: solving real-world challenges with high technology, breakthrough thinking, and multidisciplinary collaboration.

Why not change the world?