Introduction
Professor Dame Janet Thornton, DBE, FRS, FMedSci, is a Senior Scientist at the European Molecular Biology Laboratory European Bioinformatics Institute (EMBL-EBI). She is one of the world’s leading researchers in the field of structural bioinformatics [1, 2, 3]. Her research work and career have significantly advanced the fields of structural biology and protein science, especially the understanding of protein structure, function and evolution [3, 4, 5]. She is considered, along with others, as a pioneer of structural bioinformatics and she has played a profound, decisive and indispensable role in the development of the field [3, 4, 5, 6].
Through her career, as a Professor at Birkbeck and UCL, then as Director of the EMBL-EBI in Cambridge from 2001-2015, Janet has been one of the leading figures in the UK helping researchers capitalise on the bioinformatics boom, which has seen the rapid rise in sequencing, protein data, and computational methods for analysing biological data [1, 5, 6]. Janet been instrumental in overseeing the expansion of bioinformatics as a field [1, 6].
In addition to her extensive interdisciplinary research career in structural bioinformatics, Janet has led and participated in several initiatives and collaborations that have helped expand the reach and impact of the field of bioinformatics, increasing its impact on biological and biomedical research [2, 3, 4, 6]. These initiatives include ELIXIR, a pan-European infrastructure for biological data, and Biosapiens, a European virtual institute for genome annotation [3, 4, 7].
Janet has won a number of awards and honours for her contributions to life sciences. She became a Fellow of the Royal Society (FRS) in 1999, a member of the European Molecular Biology Organization (EMBO) in 2000, a Fellow of the Academy of Medical Sciences (FMedSci) in 2014, and a Fellow of the US National Academy of Sciences in 2003 [ 1, 7, 8, 9]. She was awarded a CBE in 2002 and was appointed a Dame of the Order of the British Empire in 2012 for her service to bioinformatics [1, 5, 7, 8, 9].
It is difficult to overstate Janet’s profound impact on the fields of life sciences and computational biology, through her extensive research work, her mentorship of scientists who have become scientific leaders in their own right, and through her leadership of various computational biology institutes, consortia, collaborations, and resource developments.
Link: Q&A with Professor Dame Janet Thornton
Educational and Research Background
Janet began her scientific career in physics, having done her undergraduate degree in physics at the University of Nottingham [1, 4]. Her transition into biology and biological sciences started when she started her PhD in 1970, at the National Institute for Medical Research, where she did her research on the structure of dinucleotides [1, 4]. As she did not have a background in biology, she also did a Master’s (MSc.) in biophysics at King’s College, London in her first year to help her with the transition to biology [1, 4]. Despite doing the Master's, however, Janet found the start of her PhD quite difficult and almost quit after 18 months to become a hospital physicist [4]. She decided to finish her PhD, however, and found her interest and enthusiasm for structural biology increasing [1]. By the time she finished her PhD she had decided she wanted to stick with basic research [1]. At the time, Janet did not have a particular plan, but pursued what she enjoyed, and found that “her enjoyment - and success - increased as she moved deeper into the field of computational biology” [4].
After completing her PhD, Janet became a research fellow and systems administrator in the crystallography lab of Professor David Phillips at Oxford University [1, 6]. David was a founding leader in structural biology [6]. While in David’s lab, Janet began trying to understand how protein sequences affected their three-dimensional structure [1, 6]. Her work formed the basis of her interest in finding simple patterns in “apparently complex or unordered structures” [1, 6].
Relevant Link: What is structural biology
In 1980, she joined the crystallography department of Birkbeck College, London, as an advanced fellow in the lab of Professor Sir Tom Blundell, a well-known and respected structural biologist [1, 6]. There she continued studying sequence-structure relationship of proteins [6]. She collected and sorted details of proteins structures (initially in a big blue lab book) and formed the idea of developing a system to classify protein structures in some hierarchical way [6]
In 1990, Janet became the Professor and Director of the Biomolecular Structure and Modelling Unit in the Department of Biochemistry and Molecular Biology at University College London (UCL) [1,4,7]. She then held a joint appointment at UCL and the Bernal Chair in the Crystallography department at Birkbeck [1, 4]. While at Birkbeck, then as a professor at UCL, Janet worked on, and supervised, a number of important projects that would go on to become critical to the field of structural bioinformatics.
In 1991, she supervised Professor Christine Orengo as a postdoctoral fellow. Christine used a method called SSAP, which she had developed in the lab of Dr. Willie Taylor, to implement Janet’s idea of creating a hierarchical system to classify protein structures [4]. In collaboration with Professor David Jones and others, Christine put together the CATH classification of protein structure database, which classified protein structures in a hierarchical manner to help understand their evolution and function [1, 4, 7]. The CATH database went on to become one of the most widely used databases for studying protein classification, function, and evolution [11]. The CATH database website is still maintained and updated by the Orengo group at UCL and has millions of monthly hits from researchers around the world [11].
In addition to CATH, another widely used bioinformatics tool that came out of Janet’s group was PROCHECK, a tool that helps experimental biologists ensure that structures they determine for their proteins comply with physicochemical rules [4]. PROCHECK was developed by Dr. Roman Laskowski while he was in Janet’s lab and become a widely used tools in structural biology [4]. PROCHECK is still used and maintained by Roman, although other tools have been developed since for similar purposes [4].
In 1992, Professor David Jones, who was a PhD student in Janet's lab, worked with Janet and with Dr. Willie Taylor at NIMR to develop a method known as protein threading. Protein threading predicted protein tertiary structures by “threading” a protein’s sequence onto a framework of existing protein folds to find the most energy-efficient fit [1, 6]. The work was a significant development for the prediction of protein structures and was later developed into the THREADER and GenTHREADER methods which are still available on the Bioinformatics website at UCL [10].
In 1998, while at UCL, Janet, along with a number of her colleagues, helped set up a small drug discovery company called Inpharmatica, which was set up with the goal of using bioinformatics and chemo-informatics to improve target identification for drug discovery [4, 6]. The company grew to over 100 people and did very well, but was eventually disbanded into different parts and acquired by the biotechnology company Galapagos in 2006 [6, 12]. The ChEMBL database, which was developed at the company, was eventually purchased by the Wellcome Trust and set up at EMBL-EBI and has since been very well used in both industry and academia [6].
Relevant Profile: Feature Profile: Professor Christine Orengo [former postdoc in Janet's group]
From 2001-2015, Janet was the Director of EMBL-EBI [1, 3, 4, 7, 8]. The EBI provides core bioinformatics services, especially in the form of publicly available genome and protein data, small molecule data, as well as proteomics, metabolomics, and transcriptomics data with the aim of helping researchers navigate and use massive amounts of biological data [3, 8]. The institute also performs investigator-led bioinformatics research [3, 8]. As director, Janet was able to help guide strategic developments in the institute and in field of bioinformatics [5]. Under Janet’s leadership, the Institute dramatically expanded its research activities [1].
In 2015 Janet stepped down as director of EMBL-EBI and is now a Senior Scientist at the EBI, where she leads a group of bioinformaticians in studying how enzyme catalysis, protein sequence variants, and small molecules cause diseases [3]. In addition, her group does work using computational approaches to study the causes and impacts of ageing [3, 7].
Janet’s research, leadership, and passion for computational biology have had profound and fundamental impacts on the fields of biology, biomedical science, and bioinformatics research. She has played a key role in shaping the current landscape of structural bioinformatics in Europe and abroad. She was Vice-President of the European Research Council from January 2019 to December 2020 and was responsible for the Life sciences domain [3].
Janet has said that more than any of her research breakthroughs or awards, she is most proud of her students and postdocs, many of whom have gone on to have research groups and labs of their own [4]. She has collaborated with and supervised several people who went on to become powerhouses in bioinformatics. She still has long-term collaborations with many previous members of her group, including Professor Christine Orengo and Dr. Roman Laskowski, who is now a senior staff scientist in Janet’s group at the EBI [4].
Relevant Profile: Feature Profile: Dr. Sarah Teichmann [former postdoc in Janet's group]
When she is not doing research work, Janet enjoys spending time with her family and friends and keeps in touch with colleagues and former students and postdocs [4]. Janet also enjoys spending time in her garden and in nature, as it was a love of nature and living things that first sparked her love for and interest in biology [4, 6, 9].
Janet: “I enjoy understanding how living things work and marvelling at the beauty of nature from the molecular to whole organisms. Proteins and their structures are elegant, intricate and amazingly beautiful. Understanding their evolution and the consequential evolution of life has been a terrific pleasure – and there's still a long way to go.”
Janet: "Enjoying what you do in life is really one of the most important things. If if you're lucky enough to do something that you really enjoy, it is wonderful because there is nothing like the high you get from research going well"
Janet: “The people I have met through my work have been one of the great delights of my career. I have always worked with PhD students and it is wonderful to watch them participating in this research field."
Publications:
Janet has been an author on over 600 journal articles, with over 120,000 citations. A full list of her publications can be found here
The following is a list of highlighted publications that include work discussed in this profile:
Todd, A.E., Orengo, C.A. and Thornton, J.M. 2001. Evolution of function in protein superfamilies, from a structural perspective. J Mol Biol: 307(4), 1113-43. Available at: https://pubmed.ncbi.nlm.nih.gov/11286560/.
Orengo, C.A., Michie, A.D., Jones, S. Jones, D.T., Swindells, M.B., and Thornton, J.M. 1997. CATH – a hierarchic classification of protein domain structures. Structure: 5, 1093-1109. Available at: https://www.sciencedirect.com/science/article/pii/S0969212697002608.
Orengo, C.A., Jones, D. T., and Thornton, J. 1994. Protein superfamilies and domain superfolds. Nature: 372, 631–634. Available at: https://www.nature.com/articles/372631a0.
Laskowski, R.A., MacArthur, M.W., Moss, D.S., and Thornton, J.M. 1993. PROCHECK: a program to check the stereochemical quality of protein structures. Journal of Applied Crytallography: 26. Available at: https://scripts.iucr.org/cgi-bin/paper?gl0276.
Jones, D.T., Taylor, W.R. & Thornton, J. 1992. A new approach to protein fold recognition. Nature: 358, 86–89. Available at: https://www.nature.com/articles/358086a0.
Sternberg, M.J. and Thornton, J.M. 1985. Prediction of protein structure from amino acid sequence. Nature: 271, 15-20. Available at: https://www.nature.com/articles/271015a0.
Resources:
1. Ebi.ac.uk. n.d. Janet Thornton | EMBL’s European Bionformatics Institute. [online] Available at: https://www.ebi.ac.uk/about/people/janet-thornton.
2. Microbiologyresearch.org. n.d. Microbial Genomics: Standing on the Shoulders of Giants | Microbiology Society. [online] Available at: https://www.microbiologyresearch.org/sotsog/janet-thornton.
3. ERC: European Research Council. 2021. Dame Janet THORNTON. [online] Available at: https://erc.europa.eu/erc_member/dame-janet-thornton.
4. Dhillon, P. and Thornton, J., 2020. In conversation with Janet Thornton. The FEBS Journal: 287, 4106-4113. Available at: https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.15567.
5. Royalsociety.org. n.d. Janet Thornton | Royal Society. [online] Available at: https://royalsociety.org/people/janet-thornton.
6. Zagorski, N., 2005. Profile of Janet M. Thornton. Proceedings of the National Academy of Sciences, 102, 12296-12298. Available at: https://www.pnas.org/content/102/35/12296.
7. Ebi.ac.uk. n.d. Janet Thornton | EMBL’s European Bionformatics Institute. [online] Available at: https://www.ebi.ac.uk/about/people/janet-thornton.
8. HDR UK. n.d. Janet Thornton - HDR UK. [online] Available at: https://www.hdruk.ac.uk/people/janet-thornton/.
9. Exeter.ac.uk. n.d. Professor Dame Janet Thornton FRS | Living Systems Institute | University of Exeter. [online] Available at: https://www.exeter.ac.uk/livingsystems/team/honorary/thornton.
10. Bioinf.cs.ucl.ac.uk. n.d. UCL-CS Bioinformatics: Threader. [online] Available at: http://bioinf.cs.ucl.ac.uk/software_downloads/threader/
11. Ismb.lon.ac.uk. n.d. Christine Orengo ISMB – ISMB. [online] Available at: http://www.ismb.lon.ac.uk/christine-orengo/.
12. Science|Business. 2006. Galapagos acquires UCL spin out in €12.5M all-share deal. [online] Available at: https://sciencebusiness.net/news/72901/Galapagos-acquires-UCL-spin-out.