Susan Lindquist - Research

Research

Lindquist is best known for her research that provided strong evidence for a new paradigm in genetics based upon the inheritance of proteins with new, self-perpetuating shapes rather than new DNA sequences. This research provided a biochemical framework for understanding other mysteries in biology, such as Alzheimer's disease and Creutzfeldt-Jakob disease. She is considered an expert in protein folding which, as explained by Lindquist in the following excerpt, is an ancient, fundamental problem in biology:

"What do "mad cows", people with neurodegenerative diseases, and an unusual type of inheritance in yeast have in common? They are all experiencing the consequences of misfolded proteins. ... In humans the consequences can be deadly, leading to such devastating illnesses as Alzheimer's Disease. In one case, the misfolded protein is not only deadly to the unfortunate individual in which it has appeared, but it can apparently be passed from one individual to another under special circumstances - producing infectious neurodegenerative diseases such as mad-cow disease in cattle and Creutzfeld-Jacob Disease in humans."

--from "From Mad Cows to 'Psi-chotic' Yeast: A New Paradigm in Genetics," NAS Distinguished Leaders in Science Lecture Series, November 10, 1999.

Lindquist worked on the PSI+ element in yeast (a prion) and how it can act as a switch that hides or reveals numerous mutations throughout the genome, thus acting as an evolutionary capacitor. She also proposed that a heat shock protein, hsp90, may act in the same way, normally preventing phenotypic consequences of genetic changes, but showing all changes at once when the HSP system is overloaded, either pharmacologically or under stressful environmental conditions. Most of these variations are likely to be harmful, but a few unusual combinations may produce valuable new traits, spurring the pace of evolution. Cancer cells too have an extraordinary ability to evolve. Lindquist's lab investigates closely related evolutionary mechanisms involved in the progression of cancerous tumors and in the evolution of antibiotic-resistant fungi.

Recently, Lindquist has made advances in nanotechnology, researching organic amyloid fibers capable of self-organizing into structures smaller than manufactured materials. Her group also developed a yeast “living test tube” model to study protein folding transitions in neurodegenerative diseases and to test therapeutic strategies through high-throughput screening. She is a co-founder of FoldRx, a company developing drug therapies for diseases of protein misfolding and amyloidosis.

Dr. Lindquist lectures nationally and internationally on a variety of scientific topics. In June 2006, she was the inaugural guest on the "Futures in Biotech" podcast on Leo Laporte's TWiT network. In 2007, she participated in the World Economic Forum in Davos, Switzerland with other MIT leaders.