Louise Johnson remembered
Scientists from around the world have been remembering Louise Johnson, one of the pioneers of protein crystallography, who passed away on 25 September 2012.
Credit: Anne-Katrin Purkiss, Wellcome Images
With her in-depth knowledge of X-ray crystallography combined with a long-standing interest in biochemistry, Louise made major contributions to the emerging field of structural biology. Her work deciphering the structure of lysozyme, and following this ribonuclease S, glycogen phosphorylase and cell cycle regulatory proteins, transformed our understanding of how complex biochemical and cell-biological systems work.
The impact of Louise’s activities was felt at both a national and international level. She led the development of the UK synchrotron, the Diamond Light Source near Didcot, as Diamond’s Life Science Director. In this role, she oversaw the building and development of this highly effective national facility. She also worked energetically to support and encourage scientists in developing countries to establish effective research laboratories.
Louise’s scientific career began with a degree in physics at University College London. In 1962, she embarked upon a PhD at London’s Royal Institution under David Phillips, a pioneer of protein crystallography.
Building on these early studies, Louise was interested in using an understanding of structure to uncover fundamental biochemical mechanisms. Her contribution was to work out the structure of lysozyme, the second protein and first enzyme ever solved at atomic resolution by X-ray crystallography. She determined its structure when it was bound to N-acetyl-glucosamine, a component of bacterial cell walls which inhibits lysozyme. The research led to the first structural evidence that a substrate slots into an enzyme, much as a key fits into a lock.
The team that got lysozyme: Don A. Koenig,Colin C.F. Blake, Louise N. Johnson, Tony C. North, and Raghu Sarma. David C. Phillips was away at the time. Image credit: unknown
Max Perutz emphasized the extraordinary significance of this work in an obituary he wrote for David Phillips in the Journal of Synchrotron Radiation. ‘Certain moments are deeply engraved in my memory. One is the Monday morning in March 1953 when Crick called me into his room to show me his and Jim Watson's double helical model of DNA which immediately revealed the molecular basis of heredity. Another is the moment when David Phillips, Louise Johnson and Charles Vernon made me understand how an enzyme works.’
Louise’s studies in London were followed by a short period of work at Yale University. Here, she solved the structure of the enzyme ribonuclease S, demonstrating that X-ray crystallography could be applied to complex proteins. In 1967, she returned to the UK to join Phillips who had moved to the Laboratory of Molecular Biophysics (LMB) at Oxford.
At the LMB, Louise ran a successful research group and continued to push forward cystallography and synchrotron life science research. Her group was at the forefront of those using synchrotron radiation at Daresbury Laboratory for macromolecular crystallography in the early 1980s.
Members of the Department of Zoology, Oxford, 1976 . Louise is third from the left in the front row. Image: Department of Zoology, Oxford
In 1990, Louise was appointed the first David Phillips Professor of Molecular Biophysics at Oxford. As head of the LMB she encouraged a highly cooperative working environment among the different groups which was extremely productive. From 2003, she combined her position at the LMB with the role of Life Sciences Director at Diamond.
Highlights of Louise’s research during her 40 years at Oxford are numerous. They include the determination of the structure of glycogen phosphorylase, a large and complex enzyme, which showed how an enzyme may be regulated by reversible phosphorylation, and ground-breaking studies on cell cycle cdk/cyclin complexes.
As well as carrying out cutting-edge research, Louise nurtured numerous careers, training a generation of crystallographers in Oxford who themselves now train future leaders across the world. Her book on protein crystallography with Sir Tom Blundell, published in 1976, became a classic textbook for students and researchers alike.
Professor Elspeth Garman, whose career moved from nuclear physics to protein crystallography thanks to Louise’s influence, comments that Louise had some admirable qualities. ‘Nothing could ruffle her - she was very calm and rode above the nitty-gritty. Believing in the best of people, she always got the best out of them.’
Louise Johnson with Ian Clifton in front of the Evans & Sutherland PS300 graphics station in the Rex Richards Building, Oxford. Image courtesy of Janos Hajdu
She was also considerate and caring towards her colleagues, says Elspeth. ‘She respected the fact that meetings after 4pm were impossible for some staff and she would never schedule meetings then. And she always made an appearance at lab gatherings, showing that she thought all staff were important.’
Elspeth recalls that, despite her seniority, Louise managed to stay in touch with what daily research involved. ‘Although Louise did not normally accompany us on the trips to the synchrotron, during one of her sabbatical terms, she asked to be brought up to speed in using the current X-ray equipment and software for crystallography. She determinedly and methodically worked her way through our usual training programme for new researchers, asking penetrating and pertinent questions at every stage.’
Louise also demonstrated very clear long-term vision, says Elspeth. She could see the ‘big picture’ and where the work was leading, and helped to open up new areas of research in the field.
Professor Jane Endicott, a long-term collaborator of Louise, notes another of Louise’s special qualities – enthusiasm. ‘Louise’s enthusiasm for science and for doing experiments was infectious and inspirational,’ she comments.
When, as a post-doc, Jane met regularly with Louise, she would come out of the meetings conscious that she had met with someone who embodied Kipling’s ideal of treating the twin impostors of triumph and disaster equally. Jane recalls that ‘although Louise helped enormously to keep an even keel when it was disaster that presented itself, anyone who had the privilege of reporting a good result to her will remember with great affection the enthusiastically-offered word “Splendid”.’
Ground-breaking ceremony on the Diamond Light Source campus. Image courtesy of Diamond Light Source
Professor Martin Noble, who similarly spent many years working for and with Louise, has equally fond memories.He recalls some of the lessons that Louise had learned from others and passed on to her colleagues and friends.
One of these was a warning that she offered, quoting from Aaron Klug, saying: ‘A full diary is the enemy of good research’. Martin adds that Louise is not alone in offering this advice, but is maybe unique in heeding it. ‘Despite her many accomplishments and commitments she would always find time to share in an exciting result, or to puzzle at how to overcome an intransigent problem,’ he remembers.
Louise retired from the LMB and the Life Sciences Directorship in 2007 and 2008 respectively, but continued to work at Diamond and more recently in the department, where she was finishing papers with colleagues.
Her influence will be widely felt and is deeply appreciated, as demonstrated by some of the comments which Elspeth has received from ex-LMB members since Louise’s death was announced. One colleague simply said: ‘After working in other places, only now do I realise what a special place it was under her leadership.’