Proteins run amok
Proteins in cells can sometimes start behaving badly as the human body ages.
By Joe DiGiovanni, Jour ’87
When these proteins “misfold” and aggregate and become what scientists call amyloids, it can cause a host of problems, including Alzheimer’s and Parkinson’s diseases.
Dr. Anita Manogaran, assistant professor of biological sciences, is studying prevention — specifically how to prevent protein amyloids from forming and causing damage. This research could one day contribute to the development of therapies targeting diseases, including Alzheimer’s and Parkinson’s.
Manogaran and her team are looking at the mechanics of a process called protein quality control. Understanding how these control processes work is key to determining how to prevent proteins from misfolding and forming amyloids. The key may be found in young cells, which seem to have fewer problems in protein misfolding. “How does a young cell naturally keep misfolding proteins from causing problems?” Manogaran asks. “By learning how young cells solve the problem, we may be able to develop therapies that will help combat protein misfolding in old cells.”
Studying the initial appearance of a misfolding protein is extremely challenging in mammalian systems, so these researchers are focusing on misfolding-prone proteins in quickly reproducing yeast cells. “It distills our work down to basic systems,” Manogaran says. “We can closely study the fundamental questions underlying amyloid formation in a living organism.”
Alzheimer’s and Parkinson’s diseases develop more often in older patients, but the amyloid proteins that are associated with these diseases are thought to build up in the brain many years before symptoms appear.
A study Manogaran and Dr. Stephen J. Merrill, professor of mathematics, statistics and computer science, completed earlier this year found specific amyloid proteins, called prions, are infectious when newly formed.
Manogaran and her team used 4-D live cell imaging, biochemistry and protein transfection techniques to observe how the prion amyloids form in the cell in order to learn more about these early stages of amyloid formation. This new study showed there are multiple ways prions can form to become infectious, suggesting that prion formation is more complex than previously thought. •