Chris Dobson, Master of Protein Folding Research, Dies at 69
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Researchers are mourning the untimely passing of a pioneer 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
References
News Citations
- "Insight" into Protein Folding
- Amyloidoses—Native and Synthetic Fibril Formers Offer Clues
- Aggregation Alchemy: Dobson Reviews Therapeutic Approaches
- Make or Break—Equation of Everything Fibrillar?
- Aβ Fibrils Drive Oligomer Formation, New Model Suggests
- Bexarotene in AD—New Twist to its M.O.
- Shaping Up Amyloid Toxicity: Does It Compute?
- Single-Molecule Study Zeroes In on α-Synuclein Oligomers
Further Reading
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Comments
Max-Planck-Institut für Biochemie
I have known Chris Dobson for more than 25 years. He was one of my closest colleagues and a true friend. We got to know each other during a conference in England, and he spontaneously invited me and my wife, Manajit, to come to Oxford to discuss possible collaborative research on chaperonins with him and his colleagues Sheena Radford and Carol Robinson. In contrast to some others in the protein-folding field, Chris immediately embraced the new view of chaperone-assisted protein folding.
Chris was an innovator and a visionary. His original insights into the mechanisms of protein folding and aggregation were paradigm-changing and will have a lasting impact. Besides being an exceptional scientist, he was also a passionate mentor. He had a warm and generous personality. We will never forget the wonderful times we were able to spend with him and his wife, Mary. Chris was a remarkable person, a true English gentleman.
University of Cambridge
Chris was a truly exceptional scholar and scientist whose work transformed the study of protein-aggregation diseases, but also a remarkable person whose sharp wit, visionary leadership, and generosity were widely admired. 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. We are very, very sad to lose one of the most eminent chemists of a whole generation, a much loved and admired colleague, and a friend. His legacy will live on through the work of all those whose lives he has touched and enriched in so many ways.
Lund University
Chris Dobson has made a tremendous impact on the field of neurodegenerative disease. His findings that the formation of amyloid fibrils, as well as oligomer toxicity, are grossly sequence-independent have changed the way we think in this field. Chris has been an invaluable colleague and friend. I have enjoyed numerous deep scientific discussions with Chris, in which no aspect or phenomenon was ever established enough not to deserve rethinking. He has also generously shared his views on how to mentor the next generation of brilliant minds to let them reach their full potential. The world will be a lesser place without him.
University of Florence
One would need many pages to describe just the major contributions provided by Chris Dobson to science.
The first significant contribution was on elucidating the principles of protein folding, using a number of proteins as models, such as lysozyme.
At the end of the ’90s, Chris’ intuition led him to discover that in addition to folding, proteins can also misfold and aggregate into well-structured fibrillar structures, such as amyloid fibrils, which had been thought before to be a prerogative of a small number of proteins associated with disease. Proteins could form not just amyloid-like fibrillar aggregates, Chris found, but also form oligomers during the process that could be highly toxic to cells, leading to the principle that even our own proteins living in our body can easily transform into toxins. With a large group and with many collaborators, Chris started to elucidate the fundamentals of protein aggregation, including how mutations affect the process, which regions of the sequence promote it, how oligomers mediate their toxicity, and how the kinetics of amyloid fibril formation can be treated analytically, ultimately dissecting the various phases of aggregation and the effect of external agents on them.
Chris’s contribution led to more than 840 papers, including 38 contributions in the three top journals, Nature, Science, and Cell. His papers have been cited almost 80,000 times and his H-index is as high as 135 (source Scopus). They are highly impressive numbers.
But in my opinion, an even more important element of his legacy is the many students and postdocs whom he was able to motivate, stimulate, support, strengthen, reassure, who overall became self-confident and fully independent, regardless of their personality, native language, or nationality. Over 100 of them obtained group leader positions and some of them are renowned experts in the their own fields, with international reputations, including a few who are working in the same field of protein misfolding and its link to neurodegeneration that was so central to Chris Dobson’s research.
After I finished my Ph.D. in Belgium, I was exploring options to do a postdoc. I was particularly interested in advancing the understanding of Alzheimer’s disease and wanted to apply my knowledge of biophysical chemistry to do so. When I discussed this ambition with the senior researchers in this field whom I knew in Belgium, they all pointed in one direction: Chris Dobson was the scientist who had put this field on the map, perhaps created it, and not only that, he had also supported so many junior researchers in this emerging field that everywhere I looked, someone told me about how much they learned from Chris or how they wouldn’t be where they were without Chris.
Needless to say, I was delighted when Chris accepted my application to work with him in Cambridge, and 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. Chris leaves two legacies, one in the form of his science, which has tremendously advanced the global understanding of conditions such as Alzheimer’s disease, and one in the form of a large community of colleagues, researchers, and students, by whom he will be greatly missed and remembered as, above all, an incredibly kind and supportive person.
Discovery Research MRL UK, MSD
I had the privilege of doing my Ph.D. in Chris Dobson's lab. Under his guidance, not only did I learn how to be a better scientist at the lab bench, but also how to conduct myself as a researcher. I am eternally grateful for his kind words and unwavering encouragement, and incredibly proud to have known him. He leaves a tremendous scientific and personal legacy behind him, and has paved the way for an exciting future in the field of protein misfolding.
Wren Therapeutics
Chris Dobson transformed the field of protein misfolding and aggregation, dramatically advancing our understanding of Alzheimer's disease and related disorders. He pioneered the introduction of powerful chemical and biophysical approaches, reshaping our understanding of the fundamental principles that drive these complex systems. His immense scientific contributions are overshadowed only by the kindness and generosity that he showed to all those that he interacted with. Chris supported and inspired a whole generation of scientists as an adviser, mentor, and friend, and he leaves behind a vast scientific family, many of whom are now world-leading experts in their own right.
I met Chris for the first time when, on a Saturday afternoon some years ago, he invited me to the Master's Lodge at St John's College, Cambridge, to discuss the possibility of undertaking a Ph.D. under his supervision. What struck me at the time was how Chris was interested in my aspirations and ideas, speaking to me as an equal, just as he treated everyone with whom he interacted. The unwavering support and generosity that Chris offered in that first meeting proved to be a constant over the next decade, as each and every one of his students and collaborators found it to be. Together, we traveled the most exciting of scientific journeys, working to understand the kinetics of protein misfolding and aggregation, and how this could be modulated, eventually leading to the formation of a startup company, Wren Therapeutics, whose mission is to develop new treatments for currently incurable illnesses such as Alzheimer's and Parkinson's diseases.
Chris will be missed greatly. His legacy will live on not only in the science he has left us, but also in our continuing journey, and the journeys of all of those whom he has inspired and supported.
University of Florence
I knew Chris at the end of 1980s when he was still in Oxford. Since then, for many years I had a stimulating scientific collaboration with him in many aspects of protein folding, misfolding, aggregation, and aggregate toxicity, leading to co-authoring 23 papers. He was a great protein chemist, but the biological and cellular aspects of his scientific interests intrigued him in depth, such that he became progressively also a great biochemist and cell biologist. Together with with Fabrizio Chiti, we first showed that the early oligomeric assemblies were the most highly cytotoxic amyloids, even in the case of peptides/proteins not associated with any amyloid disease, leading us to propose some shared basic mechanism of cytotoxicity. I will really miss Chris, a great scientist, a delightful person, a true English gentleman.
Various
Chris Dobson was, first and foremost, a terrifically unique person in every way. A great family man and, in his profession, caring, thoughtful, sincere, honest, humble, and always treating everyone he met, no matter who they were, in an even-handed and respectful manner. From a science point of view, his work, and following on from his collaboration in the field with the late Dr. Dale Schenk, will ultimately be proven as correct: that the key to unlocking and providing clinical relief to the myriad of protein misfolding diseases (with Alzheimer’s being the most notorious) is to target protein pathology. Chris always used to say, “While there have been many misses over the previous two decades from a clinical trial point of view, just because it is hard to do does not mean it is the wrong thing to do.” By taking a physical science and kinetic system approach to this human biological problem, Chris and his colleagues have provided mankind with the keys to solving what has been—so far—an intractable scientific and clinical problem. Chris’s full contribution to the world will become more visible in the near term, as his completely unique approach to solving protein misfolding is understood and incorporated into the field.
University of Cambridge
Chris Dobson has made major contributions that have helped shape our current understanding of the normal and aberrant behavior of proteins. His research primarily concerned the fundamental principles that regulate the folding, misfolding and aggregation of proteins and their links with human disease. He had the ability to transcend his own discipline and span across different fields. In this way, he has been profoundly influential, by recognizing that the same physical and chemical principles that determine the behavior of proteins in the test tube translate to physiological environments. This observation has opened the way for highly quantitative mechanistic studies in model systems, which in turn are leading to rational pharmacological interventions for a wide range of human conditions, which include Alzheimer’s and Parkinson’s diseases and Type II diabetes. I have no doubt that his scientific vision will eventually prove to be correct and result in effective treatments for these devastating disorders.
For those who had the privilege to meet him, Chris was a kind and inspiring person. He had the rare ability and dedication to help others fulfill their potential. Nothing gave him more pleasure than to witness the growth and success of those working with him. He was capable of offering stability and understanding to all those around him, which often resulted in the transformation of their lives. His example and his spirit will remain with us for many years to come.
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