When proteins in our body work properly, we can see, smell, consume and digest food, grow muscle and brain cells. But when these infinitely useful biological building blocks fail, the most pernicious diseases arise. Susan Lindquist has scrutinized the complex origami-like shapes of proteins and come to understand how structural mistakes can lead to a frightening class of neurodegenerative disorders, including “Mad Cow Disease.”
It turns out that misfolding in just one part of a protein can transform it from a helpful agent to an infectious material capable of replicating itself. Over time, these misshapen proteins, called prions, run roughshod in the brain, leaving holes where normal cells once functioned. The evolution of this disease may take decades in humans, so Lindquist has teamed up with yeast, which can produce millions of generations of cells in a short time, and provide the perfect laboratory for studying prions. In fact, says Lindquist, “yeast cells share an amazing variety of basic biology with humans—as different as we are physically.” Lindquist is now systematically looking in yeast for factors “that predispose proteins to get into trouble” and for chemical compounds that can reverse these malfunctions. These compounds may turn into the next generation’s cure for Alzheimer’s or Parkinson’s disease.
Susan L. Lindquist is a pioneer in the study of protein folding. She works not only with bakers’ yeast, but also with fruit flies, the plant Arabidopsis and mammals. Her labs use genetics, molecular and cell biology to understand the mechanisms of prion propagation, generation of diversity and human disease.