Susan Lindquist wins HHMI appointment

CAMBRIDGE, Mass. (May 16, 2006) — Whitehead Member Susan Lindquist has been appointed an Investigator of the Howard Hughes Medical Institute (HHMI). Lindquist will remain at Whitehead Institute while HHMI employs her and funds a large percentage of her research.

“HHMI allows scientists to undertake high-risk, high-payoff research without worrying about short-term deliverables and grant cycles,” says Lindquist. “I can now move forward with what I hope will be visionary projects.”

Most public funding for science is earmarked for specific projects. HHMI, on the other hand, supports specific people. HHMI identifies smart, creative scientists with proven track records and gives them money with virtually no strings attached. These investigators can pursue projects deemed risky by traditional funding sources and change course as they follow their scientific instincts.

Before coming to Whitehead and serving as Director from 2001 to 2004, Lindquist was an HHMI Investigator for 13 years at the University of Chicago, where she studied protein folding. HHMI funding allowed her to conduct several high-risk studies, including one that demonstrated a role of protein folding in the process of evolution.

“The postdoctoral fellowship that was written for that work was turned down everywhere,” she says. “I was able to support the project with Hughes’ money.”

Lindquist and her colleagues uncovered the first major mechanism by which organisms can acquire complex traits rapidly. They discovered that a protein called Hsp90—which promotes the folding of a special group of proteins called signal transducers—plays a major role in this process.

Signal transducers are key regulators of cell growth and developmental fates. When organisms are exposed to stress, Hsp90 expression increases, but often not enough to fully maintain all signal transduction pathways. This means that small changes in members of these pathways that have been accumulating in the genome can suddenly exert strong effects. Most are detrimental, but when they are beneficial, selective breeding can enrich the genetic changes, creating organisms with new traits.

While some researchers in Lindquist’s lab still study this mechanism, most are working on other aspects of protein folding, conducting experiments in fields ranging from nanotechnology to neurological diseases such as Alzheimer’s and Parkinson’s. Her lab, for example, reproduced many of the biological consequences of Parkinson’s disease in yeast cells, work that enabled other researchers to begin screening potential therapeutic drugs.

Lindquist is also well known for her studies on prion proteins, such as the one responsible for the human equivalent of mad cow disease. The “misfolded” version of the protein PrP causes other proteins to assume its aberrant form, a chain reaction that wreaks havoc in cells. Lindquist’s group established that the same type of chain reaction can have beneficial effects with different proteins.

“Sue Lindquist's work on prions is imaginative and original,” says Whitehead Member and HHMI Medical Advisory Board Member Gerald Fink. “She is just the sort of scientist that HHMI prides itself in supporting.”

"Sue Lindquist's reappointment to HHMI is a testament to the sustained excellence and creativity of her work," says Director David Page, who is also an HHMI Investigator. "Sue and her lab add to the excitement and buzz that define Whitehead science."

Whitehead Member David Bartel also holds an HHMI appointment, and 25 of the roughly 320 HHMI investigators in the nation have worked at Whitehead at some point in their careers.

“I’m excited to be part of the Hughes community again,” says Lindquist. “I’m looking forward to the cross-fertilization of ideas among Investigators.”