17 Sep 2019

Researchers are mourning the passing of a giant in the field of protein chemistry. Christopher Dobson succumbed to cancer on September 8, a month shy of his 70th birthday. Dobson, who had worked at the University of Cambridge since 2001, was the first to describe how proteins misfold into fibrils, and he developed equations to describe the kinetics of this process. His work has advanced the understanding of the toxic aggregates responsible for neurodegenerative diseases including Alzheimer’s, Parkinson’s, and frontotemporal dementia. In 2018, Dobson was knighted in recognition of his work.

Christopher Dobson

Colleagues called Dobson a visionary. “He was a true pioneer, bringing chemical thinking and methodology to the study of protein misfolding and aggregation, and he inspired a whole generation of scientists,” Tuomas Knowles at the University of Cambridge wrote to Alzforum (see his and other comments below). Sara Linse at Lund University, Sweden, agreed, “His findings … have changed the way we think in this field,” she wrote.

Dobson studied the dynamics of protein folding, how it goes awry, and how misfolding might be targeted therapeutically (Dec 2003 news; Mar 2004 news; May 2004 news). In 2009, he established an equation describing how fibrillization proceeds. He was one of the first to mathematically describe how the breakup of large fibrils could release small pieces that themselves seed nucleation of new fibrils (Dec 2009 news; May 2013 news). Scientists now recognize secondary nucleation as a major force driving the aggregation of Aβ, α-synuclein, prion protein, tau, and other proteins that cause neurodegenerative diseases. Dobson and colleagues later capitalized on this understanding of folding kinetics by looking for drugs that could disrupt this process (Feb 2016 news).

Dobson emphasized the importance of small oligomeric aggregates. He tied Aβ oligomers to toxicity in a fly model, and described how oligomers of α-synuclein act as a stepping stone to fibril formation (Oct 2007 news; May 2012 news). Dobson was an author on more than 800 papers and reviews, which together have been cited more than 80,000 times.

In 2013, Dobson co-founded the Cambridge Centre for Misfolding Diseases and, in 2016, helped establish the start-up Wren Therapeutics to develop treatments for Alzheimer’s disease. He accumulated numerous honors, including the 2014 Heineken Prize for Biochemistry and Biophysics, and the 2014 Feltrinelli International Prize for Medicine. He was knighted in 2018.

Colleagues said the many students and postdocs Dobson mentored form an important part of his legacy. “Over 100 of them obtained group leader positions, and some of them are renowned experts in their own field,” wrote Fabrizio Chiti at the University of Florence, Italy, to Alzforum. Karen Stroobants at the Royal Society of Chemistry was a postdoc in Dobson’s lab. “It has been an absolute privilege to know him, both for the scientific giant he was, and because he’s been an extraordinary mentor to me,” she wrote.

Others noted how kind, warm, and humble Dobson was. “He always treated everyone he met—no matter who they were—in an even-handed and respectful manner,” wrote Wren chairman Kelly Martin. Franz-Ulrich Hartl at the Max Planck Institute of Biochemistry in Martinsried, Germany, noted his generous nature. “Chris was a remarkable person, a true English gentleman,” he wrote.

Alzforum invites others to share memories of Chris Dobson below.—Madolyn Bowman Rogers