William C. Earnshaw completed his Ph.D. with Jonathan King at MIT in 1977. Postdoctoral training in Cambridge with Aaron Klug and Ron Laskey and Geneva with Ulrich Laemmli was followed by 13 years at the Johns Hopkins School of Medicine in Tom Pollard's Department of Cell Biology and Anatomy. In 1996 he moved to Edinburgh as a Wellcome Trust Principal Research Fellow as part of the initiative to bring modern Cell Biology research to Edinburgh. He continues to hold that fellowship today.
Bill Earnshaw’s primary goal throughout his career has been to understand how chromosomes are compacted and segregated when cells divide. He began by studying DNA packaging in bacteriophages, but then moved on to the study of mitotic chromosomes in vertebrate cells. Discoveries from the Earnshaw Lab have led to fundamental breakthroughs in the study of kinetochore structure and function and in the study of apoptotic execution. The Lab's discovery of the chromosomal passenger proteins and their role in the integrated control of chromosomal and cytoskeletal events during mitosis unleashed one of the most active areas of mitosis research.
Principal achievements of the Earnshaw Lab include the following:
• Combining small-angle x-ray scattering with conventional electron microscopy and computer modelling, Bill developed the first detailed model for the organisation of DNA packaged within the heads of double-strand DNA bacteriophages. This was confirmed 30 years later by others using cryoelectron microscopy.
• Bill's biochemical analysis of the mitotic chromosome scaffold identified key components, including DNA topoisomerase II, SMC2 and KIF4. Later genetic studies by lab members Damien Hudson, Paola Vagnarelli and Reto Gassmann revealed that SMC2 is a key architectural factor in mitotic chromosomes and provided important insights into regulation of the still mysterious factor(s) that condenses the chromosomes in mitosis.
• Bill pioneered the use of autoantibodies for identification and cloning of key chromosomal proteins. His identification and cloning of human centromeric proteins using serum from a scleroderma patient was the breakthrough that opened the way for the molecular characterisation of the metazoan kinetochore. He holds two patents for the use of cloned autoantigens as immunodiagnostics.
• Discovery of INCENP by Carol Cooke led Bill and Becky Bernat to propose the firstintegrated control mechanism for the spatial and temporal coordination of chromosomal and cytoplasmic events in mitosis by chromosomal passenger proteins. Later biochemical studies by lab members Richard Adams, Sally Wheatley, Ana Carvalho and Reto Gassmann led to identification of the chromosomal passenger complex (CPC), containing Aurora B kinase plus its targeting and regulatory subunits INCENP, Survivin and Borealin/DasraB. Studies of the CPC are now one of the most active areas of mitosis research.
• Biochemical studies of chromatin condensation in vitro by Eddie Wood led Yuri Lazebnik to develop the first cell-free system to study chromatin condensation and other nuclear events during apoptosis. This led to the first discovery and mapping of caspase cleavage sites, paving the way for detailed biochemical studies of apoptotic execution.
• While sitting in the audience at an EMBO Workshop in Heidelberg, Bill designed a synthetic DNA array that in collaboration with Vladimir Larionov and Natalay Kouprina (NIH, USA) plus Hiroshi Masumoto (Kazusa Institute, Japan) was used to obtain the first synthetic human artificial chromosome. This chromosome has a kinetochore whose activity can be modulated by engineering its chromatin environment. It is being used to study the role of chromatin modifications and RNA transcription in the maintenance and assembly of the vertebrate kinetochore
• Shinya Ohta performed the first comprehensive proteomic analysis of vertebrate mitotic chromosomes in a collaboration with Juri Rappsilber's group, identifying >4000 proteins and determining the number of copies of each per cell. To analyse the data, the two labs developed MultiClassifier Combinatorial Proteomics (MCCP) a multidimensional analyses that allows the identification of groups of proteins that co-vary in response to various biochemical and genetic treatments. This analysis is being used to develop a comprehensive list of all components of the kinetochore, to define the comprehensive pathway of kinetochore assembly and to predict the function of novel proteins.
• Bill's text book Cell Biology, co-written with Tom Pollard and illustrated by Graham Johnson, is used throughout the USA and Europe. A second edition was published in May 2007.
The work of the Earnshaw lab has been characterised by an integrated multidisciplinary approach involving methods as diverse as small-angle X-ray scattering, computer modeling, light and electron microscopy, proteomics, synthetic biology and gene knockout technology. Many of Bill's >215 refereed publications spanning the years 1973 to the present date have been highly influential. When his entire output of >275 publications is considered (excluding meeting abstracts), the publications have been cited >27,000 times - an average of 112 times each.
Bill is an elected Fellow of the Academy of Medical Sciences, the Royal Society of Edinburgh and the AAAS and a member of EMBO. He was awarded the Gregor Mendel Medal of the Czech Academy of Sciences in 2002 and an honorary Doctorate of Medicine by Charles University, Prague in 2009.