UW News

March 10, 2005

Scientist from one of top prion labs will explain ‘amazing’ biology

Prions, which have been identified as the causative agent in mad-cow disease, Creutzfeldt-Jacob disease and scrapie, a disease of sheep and goats, were identified, named and characterized by Dr. Stanley Prusiner, who received the 1997 Nobel Prize in physiology or medicine for the work.

There are normal prion (PREE-on) proteins in humans and other species, but these become altered into a form that causes other proteins to mis-fold and then form clumps. These disease-causing prions are remarkably stable, and they can arise spontaneously, be inherited or be transmitted as infectious agents.

Dr. Susan Lindquist, a member and former director of the Whitehead Institute at the Massachusetts Institute of Technology (MIT), is one of the leading researchers working out exactly how prions turn into “proteins gone bad” and what could be done to stop the process.

She will present this year’s Annual Science in Medicine Lecture at noon on Thursday, April 7, in Hogness Auditorium at the Health Sciences Center. The lecture is open to everyone. The Science in Medicine series is presented by the School of Medicine’s Office of Research and Graduate Education.

Her topic is “The Amazing Biology of Prion Proteins.” She will be talking about the work she and her colleagues have been doing with prions in a wide spectrum of life forms, ranging from yeast and plants to roundworms and mice.

In work published in 2002, Lindquist and a colleague showed that even very small amounts of prion protein, when it accumulates in a part of the cell called the cytosol, caused the death of neurons, or nerve cells, in cell cultures and in transgenic mice. Normally, proteins that mis-fold are destroyed in the cytosol as a method of quality control. But it now seems that the system may cause neuron death if overtaxed. This mechanism can cause the neurons to die even before the prions convert to the stable mis-folded state that causes clumps of aggregated protein to form.

Lindquist and her colleagues are also using their yeast model to study other neurodegenerative diseases. In a recent collaboration, she worked with Dr. Paul Muchowski in the UW Department of Pharmacology on research that established different genetic pathways in the development of Huntington’s disease and Parkinson’s disease. The yeast model has proved to be surprisingly useful for understanding some of the processes involved in neurodegenerative diseases.

Lindquist is a professor of biology at MIT, as well as a member of the Whitehead Institute, where she was director from 2001 until December 2004. She earned a bachelor’s degree from the University of Illinois at Champaign-Urbana, and then a Ph.D. in biology from Harvard in 1976. Her postdoctoral training, with support from the American Cancer Society, was at the University of Chicago and she joined the faculty there in 1978. From 1988 until 2001, she was a professor of molecular genetics and cell biology and an investigator for the Howard Hughes Medical Institute at the University of Chicago.

She lectures widely and has been active in national public science education programs. She also worked on the film “Lights Breaking,” about recombinant DNA technology, which received several prizes as a short science film, and she was a consultant to the Museum of Science and Industry in Chicago for exhibits on cell biology and genetics. In addition, she has given many lectures on women in science careers and on combining a career in science with raising a family.

She is a member of the National Academy of Sciences and of the American Academy of Arts and Sciences, and was named one of the 50 “most important women in science” by Discover magazine in 2002.