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SD Gross BFI0403 Janet Thornton Bioinformatician avant la lettre Michael Gross B ioinformatics is very much a buzzword of our time, with new courses and institutes dedicated to it sprouting up almost everywhere. Most significantly, the flood of genome data has raised the gen- eral awareness of the need to deve-lop new computational approaches to make sense of all the raw information collected. Professor Janet Thornton, the current director of the European Bioinformatics Institute (EBI), an EMBL outpost based at the Hinxton campus near Cambridge, has been in the field even before there was a word for it. Coming to structural biology with a physics degree from the University of Nottingham, she was already involved with computer-generated structural im- ages in the 1970s, when personal comput- ers and user-friendly programs had yet to be invented. The Early Years larities. Within 15 minutes, the software From there to the EBI, her remarkable Janet Thornton can check all 2.4 billion possible re- career appears to be organised in lationships and pick the ones relevant decades. During the 1970s, she did doc- software to compare structures to each to the question at hand. In comparison toral and post-doctoral research at other, recognise known folds and spot to publicly available bioinformatics the Molecular Biophysics Laboratory in new ones. Such work provides both packages such as Blast or Psiblast, Oxford and at the National Institute for fundamental insights into the workings Biopendium can provide an additional Medical Research in Mill Hill, near Lon- of evolution on a molecular level, and 30 % of annotation, according to Inphar- don. The former, then under the leader- practical benefits, as it facilitates the matica’s managers. For example, public ship of David Phillips is famous for its prediction of structural and functional domain searches for kinases would give protein crystallography work, the latter aspects from sequence data. you less than 800 examples, while for structural NMR. Thus Thornton was Biopendium came up with 973. involved with the elucidation of protein University College Launched in 1999, Biopendium was structures at a time when the explosive successful enough to allow Inpharmatica growth of structural biology was only In 1990, Thornton moved to University to grow and pursue an unusual two- beginning. During the 1980s, she worked College London (UCL), just a few hundred thronged business strategy. The com- at the department of crystallography at metres down the road from Birkbeck. UCL pany continues to sell data resources like Birkbeck College, London. Although she offered her a chair dedicated exclusively Biopendium, but it is also involved in also started raising a family during this to what we now call bioinformatics. The drug discovery collaboration based on time and was employed part-time for a new position enabled her to develop her their second big development, Pharma- number of years, she became a lecturer specific computational approach to struc- carta, which matches proteins to small and eventually a senior lecturer at Birk- tural biology to full bloom. Programs molecules, and which is available only on beck, and established her reputation in developed by her lab are used by re- the basis of collaborative agreements. In- structural biology by analysing common searchers world wide. One particularly pharmatica has forged such partnerships motifs in the growing number of known useful piece of software, now incorpo- with companies including Swiss-based protein structures. During that time, it rated in platform known as BioPendium, biotech company Serono. While the com- began to emerge from her work that, led her to the foundation of a spinout pany has successfully detached itself while the number of structures increased company, Inpharmatica, in 1998. from its academic origin in the UCL exponentially over time, the number of Biopendium is a tool to annotate new research labs – it boasts IT-heavy corpo- truly different arrangements of the sequences. It picks up all the publicly rate headquarters in Charlotte Street, polypeptide chain, the “folds”, remained available sequence data and all of the West London, along with research sites relatively small and might be limited to a more than 30,000 structures, and allows in Camden and Hemel Hampstead – surprisingly small number, perhaps less the user to compare all of them, and to Thornton keeps a close eye on it, as she than 1000. Her group started developing find even distant relationships or simi- chairs the scientific advisory committee. BIOforum Europe 4/2003, pp 178–179, GIT VERLAG GmbH & Co. KG, Darmstadt, Germany, www.gitverlag.com/go/bioint Another offshoot of Thornton’s work at currently maintains a number of public- focus is very much to train the trainers UCL is the CATH database of structural domain databases with gene and protein throughout Europe. We are hoping to domains, a systematic classification of sequences, structures, and expression establish a forum for the scientists who folds based on the hierarchical criteria of data. Using this recognised strength of the teach bioinformatics to share experi- Class, Architecture, Topology, and Homol- institute as a foundation, she is building a ences and to provide updating on new ogous superfamily. This project has re- stronger research institute, with teams technologies in bioinformatics. This mained at UCL, where a team of around from different disciplines interacting with forum is still in the planning stage.” 20 PhD students and post-docs, super- each other and with the expertise of the Meanwhile, Thornton chairs the or- vised by Christine Orengo, keeps it going database facilities. New group leaders have ganising committee for a major bioin- (http://www.biochem.ucl.ac.uk/bsm/cath_new/). already been appointed, and further posi- formatics conference to be held in Glas- During the last years at UCL, Thornton tions will be advertised in the autumn. For gow, August 2004. The third European also chaired two initiatives shared with this expansion, the core funding that the Conference on Computational Biology her former department at Birkbeck, EBI receives from the EMBL has been in- will be the first in the series to be held in namely the Joint Research School in Bio- creased to € 10 million. On top of that, the UK, and the first to be held in con- molecular Sciences and the BBSRC-funded there are major grants from the Wellcome junction with the leading annual interna- Bloomsbury Centre for Structural Biology. Trust and the European Union, among tional bioinformaices conference series others. The growing enterprise of bioin- on Intelligent Systems in Molecular Bio- EBI formatics also needs connections to the logy. It looks like bioinformatics will keep outside world. Thornton says: “We will growing bigger for some time to come. Since 1994, she has also been involved need to provide bridges between the bio- with the EBI as a consultant, and finally be- molecular data we collect and archive, and Weblinks: came the institute’s director in October the related data in chemistry, medicine or 2001, with initially a five-year tenure. other important areas of application.” www.cryst.bbk.ac.uk Birkbeck Crystallography www.biochem.ucl.ac.uk UCL Biochemistry While she keeps up her involvement with On joining the EBI, Thornton has also www.inpharmatica.co.uk Inpharmatica fundamental research, the new job is very emphasized the need to develop inter- www.ebi.ac.uk EBI much that of a mover and shaker. The ex- faces with smaller biotech companies, ponentially growing flood of of biological as well as the importance of spreading Michael Gross data requires strategic planning. As Thorn- expertise in bioinformatics. “Training is He is a science writer in residence at the school ton puts it: “we need a 5-year plan that will a very important part of the role of of crystallography, Birkbeck College, University of London. His latest book, “Light and Life” is available involve some expansion, including the need the EBI and we need to complement the from Oxford University Press. for additional space.” Part of her brief is to provisions made by the universities in See www.proseandpassion.com for details. expand the activities of the EBI, which Masters and PhD courses. Therefore our.
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