Honors and Awards 1125
The 2008 Genetics Society of America Medal
Susan Lindquist
Susan Lindquist
HE 2008 recipient of the Genetics Society of and transcriptional mechanisms, making it the stron- T America Medal is Susan Lindquist. Lindquist has gest most global change in eukaryotic gene expression completely transformed our understanding of the role known (McKenzie et al. 1975; McKenzie and Meselson of protein folding in biological systems. Her work has 1977; Lindquist 1980, 1981). She also discovered that employed, and to great effect, a zoo of powerful genetic eukaryotic cells have the unexpected capacity to discri- systems, including yeast, fruit flies, Arabidopsis, and minate between coexisting mRNAs and independently mice. She is also a fearless biochemist, employing state regulate their translation. During heat shock they of the art technologies and inventing new ones. Again translate heat-shock mRNAs with high efficiency and and again, she has shown the power of biochemistry to block normal mRNAs from translation, yet hold them expand and explicate fundamental insights gained from ready for reactivation after heat shock (McKenzie et al. genetic analysis and the power of genetics to disentangle 1975; Lindquist 1980, 1981; DiDomenico et al. 1982). intractable problems in biochemistry. Her work has In a seminal series of experiments Lindquist contin- provided paradigm-shifting insights into the most basic ued to exploit the heat-shock response to establish how aspects of cell biology, genetics, and evolution. intricate and highly orchestrated the regulation of eu- karyotic gene expression can be. Her work revealed regulation operating at the level of RNA splicing (Yost HEAT-SHOCK RESPONSE, HEAT-SHOCK PROTEINS, and Lindquist 1986, 1988, 1991), selective RNA and AND STRESS TOLERANCE protein transport in and out of the nucleus (Velazquez Lindquist’s work began with studies of the heat-shock et al. 1980; Wang and Lindquist 1998), selective RNA response when she was a graduate student at Harvard in degradation (Petersen and Lindquist 1988, 1989), Matthew Meselson’s lab. (At that time she published and selective deadenylation (Dellavalle et al. 1994). under the name Susan McKenzie.) As a second-year Her group also established that it is the heat-shock student, she was casting about for a new project when proteins themselves that turn these mechanisms off, at she bumped into a new assistant professor in the hallway every level (Yost and Lindquist 1986, 1991; Dellavalle of the biology labs. Sally Elgin told her of some exciting et al. 1994; Vogel et al. 1995). As it became clear that new work by Tissiers and Mitchell: that proteins were heat-shock proteins help to prevent and repair the made in response to heat shock in the salivary glands of damage caused by stress (a story to which Lindquist fruit flies. Lindquist decided to see if tissue culture cells also made important contributions), the extremely had the same response, which would make it tractable to elegant logic of the regulatory circuitry was revealed: as molecular analysis and provide a powerful wedge to ex- heat-shock proteins (Hsps) restore normal protein ho- plore the then murky waters of eukaryotic gene regula- meostasis they reset the damaged regulatory systems tion (McKenzie et al. 1975; McKenzie and Meselson that prevent the transcription, translation, splicing, 1977). She discovered that these cells did have the degradation, and deadenylation of normal mRNAs. By response and that it was governed by both translational restoring regulatory systems to their normal state, Hsps 1126 Honors and Awards remove their own advantage, turning off the response. lished that it was an inherent property of Sup35 itself. Due in large measure to her work (complimented by Remarkably, once a small fraction switches, it rapidly the seminal work of Spradling, Pelham, Lis, and Wu on templates the conversion of other proteins to the same transcription), the heat-shock response provides per- state. Prion1 cell lysates can template this conversion, haps the most beautiful and complete example of but not prion