On weekends, Fabrizio Chiti can be found behind the wheel of his RV, exploring the Italian countryside with his wife and daughter. A decade ago, as an undergraduate at the University of Florence, Chiti never imagined he would be doing science in his home country, let alone in the same department where he became fascinated by proteins. "I was told there were no chances for me," Chiti says. "The opportunities and funding for science were not very good in Florence at that period."
A young Chiti heeded the warning and left for the University of Oxford in 1996 to do his doctoral work with Chris Dobson. Chiti spent three years researching the folding properties of muscle acylphosphatase. Before Chiti's graduation, however, Dobson's interests shifted to protein aggregation, and Chiti was reluctant to follow. "I was deeply involved in protein folding," Chiti says. Dobson wanted his student to explore the possibility that an ordinary protein not related to disease, such as acylphosphatase, could form amyloid fibrils. "I finally asked him so many times, he did [the experiment]," says Dobson.
Despite his hesitations, Chiti's research was a major success. He demonstrated that under certain conditions, acylphosphatase can form amyloid fibrils identical to those found in diseases such as Alzheimer's and Parkinson's.
Chiti decided to focus on finding the mechanism that proteins use to avoid misfolding and aggregation. A funding opportunity became available through the Jerry Lewis-inspired Telethon Foundation, which funds Italian research on genetic diseases. With his bride-to-be in Florence, Chiti returned in 1999 to the lab of Giampietro Ramponi, where he had previously studied.
Chiti investigated aggregation from multiple angles: biochemical, genetic, statistical, and structural. With Massimo Stefani's group he showed that early protein aggregates can also be cytotoxic, implying that avoiding aggregation is more important to the cell than first imagined.
As this new direction opened up, so did a faculty position at the University of Florence. Now, as an associate professor (he skipped the assistant-professor stage, a rare promotion in Italy), Chiti's next goal is to quantify aggregation properties in vivo. Dobson calls Chiti's interdisciplinary approach the "wave of the future ... and he has done this to an extreme degree."
1. F. Chiti et al., "Designing conditions for in vitro formation of amyloid protofilaments and fibrils," Proc Natl Acad Sci, 96:3590-4, 1999. (Cited in 383 papers) 2. M. Bucciantini et al., "Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases," Nature, 416:507-11, 2002. (Cited in 527 papers) 3. F. Chiti et al., "Rationalization of the effects of mutations on peptide and protein aggregation rates," Nature, 424:805-8, 2003. (Cited in 165 papers)