Date(s) - 08/22/2014
8:00 pm - 9:00 pm
Friday Evening Lecture – Lederberg Lecture
Susan Lindquist, Whitehead Institute for Biomedical Research; HHMI
“From Yeast Cells to Patient Neurons: A Powerful Discovery Platform for Combating Neurodegenerative Diseases”
Lillie Auditorium, 8:00 PM
Introduction by Dr. Gerald Weissmann, Editor-in-Chief, The FASEB Journal; Professor Emeritus of Medicine; Research Professor, Department of Medicine, NYU School of Medicine
Many neurodegenerative diseases (NDs) arise when specific proteins misfold and then aggregate, forming complexes that disturb the biochemical processes within neurons. Although different NDs involve different proteins, the misfolded complexes are a common pathological feature. For example, Parkinson’s disease involves the protein alpha-synuclein (α-syn) and Alzheimer’s disease involves proteins Aβ and tau. Many basic biological processes within cells are highly conserved over millions of years of evolution from yeast to human. This conservation allows us to develop models for the pathologies caused by these ND-associated proteins by expressing the human proteins in yeast. Yeast offer a well-defined genetic toolbox and are much more easily manipulated in the lab than are neurons. When we express the ND-associated human proteins in yeast, the yeast grow more slowly. Through genetics, we can use these yeast to discover genes that help the yeast expressing the toxic protein to grow better. In addition, these yeast can be grown in the presence of thousands of compounds (called high throughput screening) to identify compounds that alleviate toxicity. We have found that each of our yeast models exhibits a specific mechanism of cellular toxicity, which depends on the human protein being expressed, and yields a discovery platform directly relevant to the human disease associated with that protein. Our yeast findings were validated when the same genes and compounds identified in yeast rescued neurons in other experimental organisms. Thus, these yeast discovery platforms allowed identification of genes and compounds with high therapeutic potential as well as insight into how these compounds work to alleviate the toxicity that results in neurodegeneration.
Dr. Susan Lindquist is a pioneer in the study of protein folding. She has shown that changes in protein folding can have profound and unexpected influences in fields as wide-ranging as human disease, evolution and nanotechnology. Dr. Lindquist is a Member and former Director (2001 to 2004) of the Whitehead Institute for Biomedical Research, a Professor of Biology at MIT, and a Howard Hughes Medical Institute investigator. Previously she was the Albert D. Lasker Professor of Medical Sciences at the University of Chicago (1999 to 2001), and a Professor in the Department of Molecular Biology, University of Chicago. She received a Ph.D. in Biology from Harvard University in 1976. She is a member of the National Academy of Sciences, the American Academy of Arts and Science, the American Philosophical Society and the Institute of Medicine. Her honors also include the Dickson Prize in Medicine, the Otto-Warburg Prize, the Genetics Society of America Medal, the FASEB Excellence in Science Award, the Max Delbrück Medal, the Mendel Medal and the E.B. Wilson Medal. In 2009, she was the recipient of the National Medal of Science. She was a co-founder of FoldRx Pharmaceuticals, Inc., and is currently on the board of directors of Johnson and Johnson.
About the Joshua Lederberg Lecture:
The Joshua Lederberg Lecture is sponsored by The Ellison Medical Foundation in honor of Joshua S. Lederberg, Ph.D., Nobel Laureate and founding Chair of the Ellison Medical Foundation Scientific Advisory Board. Dr. Lederberg’s insight, energy, and creativity were essential to the creation and successful development of The Ellison Medical Foundation over its first ten years.