Susan L. Lindquist, PhD

Member, Whitehead Institute Professor of Biology, MIT Investigator of the Howard Hughes Medical Institute 617.258.5184 lindquist_admin@wi.mit.edu

Whitehead Member 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 and discusses her work in a video [ 512 kbps QuickTime] and TWiT.tv "Futures in Biotech" podcast [26.5 mb mp3, or http://twit.tv/fib0077].

Protein misfolding has been implicated as a major mechanism in many severe neurological disorders including Parkinson’s and Huntington’s diseases. Lindquist and colleagues have developed yeast strains that serve as living test tubes in which to study these disorders, unraveling how protein folding contributes to them. They have succeeded in reproducing many of the biological consequences of Parkinson’s disease in yeast cells and are screening for drugs to prevent and treat the disease.

Prions are proteins that can change into a self-perpetuating form. They have only been discovered recently, but one of them is already well known as the cause of mad cow disease. The Lindquist lab investigates both how prions form and the diseases they cause. In addition, Lindquist is convinced that other prion proteins play many important and positive roles in biological processes. The first evidence for this was shown in her work with Nobel Laureate Eric Kandel, which demonstrated that prions may be integral to memory storage in the brain. The Lindquist lab has also used yeast to prove that inherited traits can be passed on via prion proteins, without any change in DNA or RNA, findings that have added a twist to traditional understanding of inheritance.

Heat shock proteins are a group of molecular chaperone proteins that, as their name might suggest, guide other proteins to fold and mature correctly. Lindquist has established that heat shock protein 90 (Hsp90) can reveal hidden genetic variation in fruit flies and in cress plants (Arabidopsis) under certain 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. This mechanism has great potential for use in creating better crop plants by conventional breeding methods, without the need for transgenic manipulations of crops. The lab is currently investigating closely related mechanisms involved in the progression of cancerous tumors and in the evolution of antibiotic resistant fungi.

Lindquist is a Member and former Director (2001-2004) of Whitehead Institute, a Professor of Biology at MIT, and a Howard Hughes Medical Institute investigator. Previously she was the Albert D. Lasker Professor of Medical Sciences from 1999-2001, and a Professor in the Department of Molecular Biology, University of Chicago, since 1978. She received a PhD in Biology from Harvard University in 1976, and was elected to the American Academy of Arts and Sciences in 1997, the National Academy of Sciences in 1997 and the Institute of Medicine in 2006.

Selected Publications

Heinrich, S.U., Lindquist, S. (2011). Protein-only mechanism induces self-perpetuating changes in the activity of neuronal Aplysia cytoplasmic polyadenylation element binding protein (CPEB). Proc Natl Acad Sci USA 108: 2999-3004.

Jarosz, D.F., Lindquist, S. (2010). Hsp90 and environmental stress transform the adaptive value of natural genetic variation. Science 330: 1820-4.

Dong, J., Castro, C.E., Boyce, M.C., Lang, M.J., Lindquist, S. (2010). Optical Trapping with High Forces Reveals Unexpected Behaviors of Prion Fibrils. Nat Struct Mol Biol 17: 1422-30.

Alberti, S., Halfmann, R., King, O., Kapila, A., Lindquist, S. (2009). A systematic survey identifies prions and illuminates sequence features of prionogenic proteins. Cell 137: 146-158.

Yeger-Lotem, E., Riva, L., Su, L.J., Gitler, A.D., Cashikar, A., King, O.D., Auluck, P.K., Geddie, M.L., Valastyan, J.S., Karger, D.R., Lindquist, S., Fraenkel, E. (2009). Bridging the gap between high-throughput genetic and transcriptional data reveals cellular pathways responding to alpha-synuclein toxicity. Nat Genet 41(3): 316-23.

Gitler, A.D., Chesi, A., Geddie, M.L., Strathearn, K.E., Hamamichi, S., Hill, K.J., Caldwell, K.A., Caldwell, G.A., Cooper, A.A., Rochet, J-C., Lindquist, S. (2009). α−Synuclein is part of a diverse and highly conserved interaction network that includes PARK9 and manganese toxicity. Nat Genet 41(3): 308-15.

Tyedmers, J., Madariaga, M.L., Lindquist, S. (2008). Prion switching in response to environmental stress. PLoS Biol 6(11): e294.

Dai, C., Whitesell, L., Rogers, A.B., Lindquist, S. (2007). Heat-shock factor 1 is a powerful multifaceted modifier of carcinogenesis. Cell 130: 1005-18.

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