Tom Blundell

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Sir Tom Blundell

FRS FRSC FMedSci FRSB MAE
Blundell Tom 280306 crop.jpg
Blundell in 2006
Born
Thomas Leon Blundell

(1942-07-07) 7 July 1942 (age 81) [1]
Brighton, England, UK
Education Steyning Grammar School
Alma mater University of Oxford (BA, DPhil) [1]
Known for
Spouse
Lady Bancinyane Lynn Sibanda
​
​
(m. 1987)​
[1]
Children3 [3]
Awards
Scientific career
Fields
Institutions
Thesis The determination by X-ray diffraction methods of the crystal and molecular structures of some co-ordination compounds  (1969)
Doctoral advisor Herbert M Powell [6]
Doctoral students
Website www.bioc.cam.ac.uk/research/blundell

Sir Thomas Leon Blundell, FRS FRSC FMedSci MAE (born 7 July 1942) is a British biochemist, structural biologist, and science administrator. He was a member of the team of Dorothy Hodgkin that solved in 1969 the first structure of a protein hormone, insulin. Blundell has made contributions to the structural biology of polypeptide hormones, growth factors, receptor activation, signal transduction, and DNA double-strand break repair, subjects important in cancer, tuberculosis, and familial diseases. [11] He has developed software for protein modelling and understanding the effects of mutations on protein function, leading to new approaches to structure-guided and Fragment-based lead discovery. In 1999 he co-founded the oncology company Astex Therapeutics, which has moved ten drugs into clinical trials. Blundell has played central roles in restructuring British research councils and, as President of the UK Science Council, in developing professionalism in the practice of science. [12]

Contents

Education

Insulin monomer Insulin worm bw.jpg
Insulin monomer

Born in Brighton in 1942, Blundell was educated at Steyning Grammar School. He was the first in his family to attend university, winning an Open Scholarship to the University of Oxford. He earned a First Class degree in Natural Sciences in 1964, then moved to research in the Department of Chemical Crystallography, first with Herbert Marcus Powell[ citation needed ] FRS for his Doctor of Philosophy degree [6] and later working on insulin with Dorothy Hodgkin.[ citation needed ] He was a Junior Research Fellow at Linacre College, University of Oxford, where he is now an Honorary Fellow.

Career and research

Blundell's early posts were at the University of Oxford and the University of Sussex. In 1976, Blundell joined the Department of Crystallography at Birkbeck, University of London, becoming head of department in 1978.

In 1991, while continuing academic research, he moved further into science administration and policy, as Director General of the Agricultural and Food Research Council (1991–94) and then the founding Chief Executive of the Biotechnology and Biological Sciences Research Council (BBSRC) (1994–1996). He is a former president of the Biosciences Federation (2004–06). In June 2011 he became President of the Science Council.

In 1995 he became the fifth Sir William Dunn Professor of Biochemistry and head of the Department of Biochemistry at the University of Cambridge; [13] he currently also holds the Chair of the School of Biological Sciences at that university. He is a fellow of Sidney Sussex College. His speciality is molecular biology and his research on identifying the chemical processes of diseases has led to the development of drugs to treat Aids, cancer, cataracts and diabetes. He is the co-founder of two drug discovery companies, Astex Technology Ltd and Biofabrika.

On 15 September 2010, Blundell, along with 54 other public figures, signed an open letter published in The Guardian , stating their opposition to Pope Benedict XVI's state visit to the UK. [14]

Blundell has been active on environmental issues, first as Chair of the Planning Committee of the Oxford City Council (1970–73), during the time when it stopped the building of a motorway through the city centre, pedestrianised much of the historic centre, and made North Oxford a conservation area. From 1998 to 2005 he was Chair of the Royal Commission on Environmental Pollution, [15] when he oversaw the production of key reports such as those on Energy – the Changing Climate, Chemicals in Products – Safeguarding the Environment and Human Health, and Turning the Tide: Addressing the Impact of Fisheries on the Marine Environment. [16] He is a Distinguished Member of Humanists UK. [17]

Original 1989 structure of the HIV protease dimer, from PDB 3PHV 3phv HIV-prot rib.png
Original 1989 structure of the HIV protease dimer, from PDB 3PHV
Glucagon hormone (red) bound to its membrane receptor 184-Glucagon glucagonreceptor.tif
Glucagon hormone (red) bound to its membrane receptor
Human DNA ligase IV, from PDB 3W5O. 3w5o DNA-ligase rib.png
Human DNA ligase IV, from PDB 3W5O.

Blundell's research interests lie in elucidating the architecture and function of macromolecules and their multi-component assemblies using methods from biochemistry, protein crystallography, and bioinformatics, with the objectives of understanding biological function, of knowledge-based prediction of structure, and of discovering new therapeutics for cancer and tuberculosis. [5] [11] Systems studied include DNA repair, hormones, growth factors and hormone/receptor interactions, cellular signalling, crystallins (lens proteins), renin and HIV protease. He has contributed 235 crystal structures to the worldwide Protein Data Bank (accessed 3/3/16). At least seven of the Molecule-of-the-Month features at the RCSB site of the worldwide Protein Databank have featured molecular structures solved and studied by the Blundell lab, such as the glucagon hormone shown at left in David Goodsell's drawing, [18] [19] nerve growth factor, [20] [21] the RAD51-BRCA2 DNA recombination complex, [22] [23] and the DNA ligase shown at right. [24] [25] His group has written several broadly used bioinformatics programs. [26] [27] [28] [29] [30] He co-authored a textbook on protein crystallography with Louise Johnson, [31] which was translated into French and Russian.

Doctoral students and postdocs

Blundell has supervised numerous Doctor of Philosophy students and postdoctoral researchers in his lab including Tim Hubbard, [7] Laurence Pearl, [8] Andrej Šali, [9] and Charlotte Deane.

Awards and honours

Blundell was elected a Fellow of the Royal Society (FRS) in 1984. [32] His nomination reads:

Professor of Crystallography, Birkbeck College, University of London. Distinguished for his work on crystal and molecular structures and biochemistry of protein hormones, enzymes, and proteins of the eye lens. He had an outstanding part in solution of the insulin crystal structure. He has related his structure for glucagon to receptor binding of this hormone. In chemically modified insulins he has studied structure-function relationships and he has proposed a model for the evolution of insulin. His work on avian pancreatic polypeptide, the acid proteinases from mammals and fungi and the proteins of the eye lens is characterised by similar extensive detail from which he disects [sic] important structural relationships and derives principles and guides on protein evolution and hormone (especially growth hormone) function. [32]

Blundell became one of the first fellows of the Academy of Medical Sciences in 1998. [33] He was elected a member of the European Molecular Biology Organisation (EMBO) in 1985; [4] A member of the Academia Europaea in 1993;[ citation needed ] Founding Member, Academy of Medical Sciences 1999. International recognition has come in his election as a Foreign Member of the Indian National Science Academy,[ citation needed ] the Chilean Academy[ citation needed ] and The World Academy of Sciences TWAS.[ citation needed ]

Sir Tom Blundell in his office at the University of Cambridge, UK Blundell Tom BIO 0031adj1-1.jpg
Sir Tom Blundell in his office at the University of Cambridge, UK

Blundell has received numerous awards and medals, including the Alcon Award for Vision Research in 1986; Gold Medal, Institute of Biotechnology in 1987; Krebs Medal FEBS 1987; Ciba Medal, Biochemical Society in 1988; Feldberg Prize in Biology and Medicine in 1988; Gold Medal, Society of Chemical Industry in 1996; First Recipient, Pfizer European Prize for Innovation in 1998 and Bernal Lecture, Royal Society 1998. [34] He received the 2013 Biochemical Society Award and Cambridge University Science Prize called the Philosophical Society Fellows Prize & Lecture 2014.[ citation needed ] Most recently in 2017 he received the 11th IUCr Ewald Prize. [35] He has been President, UK Biosciences Federation (2003–2009); President, Biochemical Society (2009–2011); and President, UK Science Council (since 2011).

Blundell's contributions were recognised by a knighthood in 1997. He has been awarded Honorary Doctorate degrees from 16 universities and was interviewed by Kirsty Young on the BBC Radio 4 programme Desert Island Discs in 2007. [36]

Personal life

Blundell married Lady Bancinyane Lynn Sibanda in 1987 [1] and has three children. [3] His brother is the economist Richard Blundell.

Blundell was elected to the Oxford City Council in 1970 as a Labour councillor for the St. Clement’s Ward. [37]

Related Research Articles

<span class="mw-page-title-main">Insulin</span> Peptide hormone

Insulin is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (INS) gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism of carbohydrates, fats and protein by promoting the absorption of glucose from the blood into liver, fat and skeletal muscle cells. In these tissues the absorbed glucose is converted into either glycogen via glycogenesis or fats (triglycerides) via lipogenesis, or, in the case of the liver, into both. Glucose production and secretion by the liver is strongly inhibited by high concentrations of insulin in the blood. Circulating insulin also affects the synthesis of proteins in a wide variety of tissues. It is therefore an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules inside the cells. Low insulin levels in the blood have the opposite effect by promoting widespread catabolism, especially of reserve body fat.

The Protein Data Bank (PDB) is a database for the three-dimensional structural data of large biological molecules, such as proteins and nucleic acids. The data, typically obtained by X-ray crystallography, NMR spectroscopy, or, increasingly, cryo-electron microscopy, and submitted by biologists and biochemists from around the world, are freely accessible on the Internet via the websites of its member organisations. The PDB is overseen by an organization called the Worldwide Protein Data Bank, wwPDB.

<span class="mw-page-title-main">Glucagon</span> Peptide hormone

Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises the concentration of glucose and fatty acids in the bloodstream and is considered to be the main catabolic hormone of the body. It is also used as a medication to treat a number of health conditions. Its effect is opposite to that of insulin, which lowers extracellular glucose. It is produced from proglucagon, encoded by the GCG gene.

<span class="mw-page-title-main">Christian de Duve</span> Belgian biochemist and cytologist (1917–2013)

Christian René Marie Joseph, Viscount de Duve was a Nobel Prize-winning Belgian cytologist and biochemist. He made serendipitous discoveries of two cell organelles, peroxisome and lysosome, for which he shared the Nobel Prize in Physiology or Medicine in 1974 with Albert Claude and George E. Palade. In addition to peroxisome and lysosome, he invented scientific names such as autophagy, endocytosis, and exocytosis in a single occasion.

<span class="mw-page-title-main">Robert Huber</span> German biochemist and Nobel laureate (born 1937)

Robert Huber is a German biochemist and Nobel laureate. known for his work crystallizing an intramembrane protein important in photosynthesis and subsequently applying X-ray crystallography to elucidate the protein's structure.

<span class="mw-page-title-main">MRC Laboratory of Molecular Biology</span> Research institute in Cambridge, England

The Medical Research Council (MRC) Laboratory of Molecular Biology (LMB) is a research institute in Cambridge, England, involved in the revolution in molecular biology which occurred in the 1950–60s. Since then it has remained a major medical research laboratory at the forefront of scientific discovery, dedicated to improving the understanding of key biological processes at atomic, molecular and cellular levels using multidisciplinary methods, with a focus on using this knowledge to address key issues in human health.

<span class="mw-page-title-main">Andrej Šali</span> American biologist (born 1963)

Andrej Šali is a computational structural biologist. Since 2003, he has been Professor in the Department of Bioengineering and Therapeutic Sciences at University of California, San Francisco. He also serves as an editor of the journal Structure.

<span class="mw-page-title-main">Glucagon-like peptide-1 receptor</span> Receptor activated by peptide hormone GLP-1

The glucagon-like peptide-1 receptor (GLP1R) is a G protein-coupled receptor (GPCR) found on beta cells of the pancreas and on neurons of the brain. It is involved in the control of blood sugar level by enhancing insulin secretion. In humans it is synthesised by the gene GLP1R, which is present on chromosome 6. It is a member of the glucagon receptor family of GPCRs. GLP1R is composed of two domains, one extracellular (ECD) that binds the C-terminal helix of GLP-1, and one transmembrane (TMD) domain that binds the N-terminal region of GLP-1. In the TMD domain there is a fulcrum of polar residues that regulates the biased signaling of the receptor while the transmembrane helical boundaries and extracellular surface are a trigger for biased agonism.

<span class="mw-page-title-main">Louise Johnson</span> British biochemist and protein crystallographer 1940–2012

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<span class="mw-page-title-main">Janet Thornton</span> British bioinformatician and academic

Dame Janet Maureen Thornton, is a senior scientist and director emeritus at the European Bioinformatics Institute (EBI), part of the European Molecular Biology Laboratory (EMBL). She is one of the world's leading researchers in structural bioinformatics, using computational methods to understand protein structure and function. She served as director of the EBI from October 2001 to June 2015, and played a key role in ELIXIR.

<span class="mw-page-title-main">Helen M. Berman</span> American chemist

Helen Miriam Berman is a Board of Governors Professor of Chemistry and Chemical Biology at Rutgers University and a former director of the RCSB Protein Data Bank. A structural biologist, her work includes structural analysis of protein-nucleic acid complexes, and the role of water in molecular interactions. She is also the founder and director of the Nucleic Acid Database, and led the Protein Structure Initiative Structural Genomics Knowledgebase.

<span class="mw-page-title-main">M. Vijayan</span> Indian structural biologist (1941–2022)

Mamannamana Vijayan was an Indian structural biologist.

<span class="mw-page-title-main">Guy Dodson</span> British crystallographer (1937–2012)

George Guy Dodson FRS FMedSci, was a British biochemist who specialised in protein crystallography at the University of York.

<span class="mw-page-title-main">David Goodsell</span>

David S. Goodsell, is an associate professor at the Scripps Research Institute and research professor at Rutgers University, New Jersey. He is especially known for his watercolor paintings of cell interiors.

<span class="mw-page-title-main">Laurence Pearl</span> British biologist

Laurence Harris Pearl FRS FMedSci is a British biochemist and structural biologist who is currently Professor of Structural Biology in the Genome Damage and Stability Centre and was Head of the School of Life Sciences at the University of Sussex.

Michael Joseph Ezra Sternberg is a professor at Imperial College London, where he is director of the Centre for Integrative Systems Biology and Bioinformatics and Head of the Structural bioinformatics Group.

Molecular Operating Environment (MOE) is a drug discovery software platform that integrates visualization, modeling and simulations, as well as methodology development, in one package. MOE scientific applications are used by biologists, medicinal chemists and computational chemists in pharmaceutical, biotechnology and academic research. MOE runs on Windows, Linux, Unix, and macOS. Main application areas in MOE include structure-based design, fragment-based design, ligand-based design, pharmacophore discovery, medicinal chemistry applications, biologics applications, structural biology and bioinformatics, protein and antibody modeling, molecular modeling and simulations, virtual screening, cheminformatics & QSAR. The Scientific Vector Language (SVL) is the built-in command, scripting and application development language of MOE.

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Progress in Biophysics and Molecular Biology is a peer-reviewed scientific journal publishing review articles in the fields of biophysics and molecular biology. It was established in 1950 as Progress in Biophysics and Biophysical Chemistry, obtaining its current title in 1963.

References

  1. 1 2 3 4 Anon (2015). "Blundell, Sir Thomas Leon, (Sir Tom)" . Who's Who (online Oxford University Press  ed.). A & C Black. doi:10.1093/ww/9780199540884.013.U7914.(Subscription or UK public library membership required.)
  2. ↑ Blundell, T.; Cutfield, J.; Cutfield, S.; Dodson, E.; Dodson, G.; Hodgkin, D.; Mercola, D.; Vijayan, M. (1971). "Atomic positions in rhombohedral 2-zinc insulin crystals". Nature. 231 (5304): 506–511. Bibcode:1971Natur.231..506B. doi:10.1038/231506a0. PMID   4932997. S2CID   4158731.
  3. 1 2 Cambridge, University of (29 March 2018). "The multi-talented scientist who finds inspiration in far-flung places". Medium.com. Retrieved 3 July 2018.
  4. 1 2 Anon (1996). "Tom L. Blundell". people.embo.org. Heidelberg: European Molecular Biology Organization.
  5. 1 2 3 4 5 Tom Blundell publications indexed by Google Scholar OOjs UI icon edit-ltr-progressive.svg
  6. 1 2 Blundell, Tom (1967). The Determination by X-Ray diffraction methods of the crystal and molecular structures of some co-ordination compounds : a study of the stereochemistry of pentaco-ordination. ora.ox.ac.uk (DPhil thesis). University of Oxford. Copac   34750152. Open Access logo PLoS transparent.svg
  7. 1 2 Hubbard, Timothy John Philip (1988). The design, expression and characterisation of a novel protein. london.ac.uk (PhD thesis). University of London. OCLC   940320228. Copac   29528696.
  8. 1 2 Pearl, Laurence (1991). Crystallographic studies of endothiapepsin. london.ac.uk (PhD thesis). London, Birkbeck College. OCLC   1000934521.
  9. 1 2 Sali, Andrej (1991). Modelling three-dimensional structure of a protein from its amino acid sequence. london.ac.uk (PhD thesis). London, Birkbeck College. OCLC   500526292. EThOS   uk.bl.ethos.415316.
  10. ↑ Deane, Charlotte (2000). Protein structure prediction: amino acid propensities and comparative modelling (PhD thesis). EThOS   uk.bl.ethos.598479.
  11. 1 2 Tom Blundell publications indexed by the Scopus bibliographic database. (subscription required)
  12. ↑ "Professor Sir Tom Blundell FRS FMedSci". British Humanist Association . Retrieved 22 March 2014.
  13. ↑ Šali, A.; Blundell, T. L. (1993). "Comparative Protein Modelling by Satisfaction of Spatial Restraints". Journal of Molecular Biology . 234 (3): 779–815. doi:10.1006/jmbi.1993.1626. PMID   8254673.
  14. ↑ "Letters: Harsh judgments on the pope and religion". The Guardian. London. 15 September 2010. Retrieved 16 September 2010.
  15. ↑ "Royal Commission on Environmental Pollution". Rcep.org.uk. Retrieved 3 July 2018.
  16. ↑ "Turning the Tide (RCEP report #25)" (PDF). Rcep.org.uk. Retrieved 3 July 2018.
  17. ↑ "British Humanist Association – Distinguished supporters:Sir Tom Blundell".
  18. ↑ Sasaki K, Dockerill, Adamiak DA, Tickle IJ, Blundell TL (1975). "X-ray analysis of glucagon and its relationship to receptor binding". Nature. 257 (5529): 751–757. Bibcode:1975Natur.257..751S. doi:10.1038/257751a0. PMID   171582. S2CID   4183707.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  19. ↑ "Glucagon Molecule-of-the-Month". Pdb101.rcsb.org. Retrieved 3 July 2018.
  20. ↑ McDonald, Neil Q.; Lapatto, Risto; Rust, Judith Murray; Gunning, Jennifer; Wlodawer, Alexander; Blundell, Tom L. (1991). "New protein fold revealed by a 2.3-Å resolution crystal structure of nerve growth factor". Nature. 354 (6352): 411–414. Bibcode:1991Natur.354..411M. doi:10.1038/354411a0. ISSN   0028-0836. PMID   1956407. S2CID   4346788.
  21. ↑ "Neurotrophins Molecule-of-the-Month". Pdb101.rcsb.org. Retrieved 3 July 2018.
  22. ↑ Pellegrini L, Yu DS, Anand S, Lee M, Blundell TL, Venkitaraman AR (2002). "Insights into DNA recombination from the structure of a RAD51-BRCA2 complex". Nature. 420 (6913): 287–293. Bibcode:2002Natur.420..287P. doi:10.1038/nature01230. PMID   12442171. S2CID   4359383.
  23. ↑ "RecA and Rad51 Molecule-of-the-Month". Pdb101.rcsb.org. Retrieved 3 July 2018.
  24. ↑ Ochi T, Gu X, Blundell TL (2013). "Structure of the catalytic region of DNA ligase IV in complex with an artemis fragment sheds light on double-strand break repair". Structure. 21 (4): 672–679. doi:10.1016/j.str.2013.02.014. PMC   3664939 . PMID   23523427.
  25. ↑ "DNA ligase Molecule-of-the-Month". Pdb101.rcsb.org. Retrieved 3 July 2018.
  26. ↑ Lewis, T. E.; Sillitoe, I; Andreeva, A; Blundell, T. L.; Buchan, D. W.; Chothia, C; Cuff, A; Dana, J. M.; Filippis, I; Gough, J; Hunter, S; Jones, D. T.; Kelley, L. A.; Kleywegt, G. J.; Minneci, F; Mitchell, A; Murzin, A. G.; Ochoa-Montaño, B; Rackham, O. J.; Smith, J; Sternberg, M. J.; Velankar, S; Yeats, C; Orengo, C (2013). "Genome3D: A UK collaborative project to annotate genomic sequences with predicted 3D structures based on SCOP and CATH domains". Nucleic Acids Research. 41 (Database issue): D499-507. doi:10.1093/nar/gks1266. PMC   3531217 . PMID   23203986.
  27. ↑ Lewis, T. E.; Sillitoe, I; Andreeva, A; Blundell, T. L.; Buchan, D. W.; Chothia, C; Cozzetto, D; Dana, J. M.; Filippis, I; Gough, J; Jones, D. T.; Kelley, L. A.; Kleywegt, G. J.; Minneci, F; Mistry, J; Murzin, A. G.; Ochoa-Montaño, B; Oates, M. E.; Punta, M; Rackham, O. J.; Stahlhacke, J; Sternberg, M. J.; Velankar, S; Orengo, C (2015). "Genome3D: Exploiting structure to help users understand their sequences". Nucleic Acids Research. 43 (Database issue): D382-6. doi:10.1093/nar/gku973. PMC   4384030 . PMID   25348407.
  28. ↑ Mizuguchi, K.; Deane, C. M.; Blundell, T. L.; Overington, J. P. (1998). "HOMSTRAD: A database of protein structure alignments for homologous families". Protein Science. 7 (11): 2469–2471. doi:10.1002/pro.5560071126. PMC   2143859 . PMID   9828015.
  29. ↑ Shi, J.; Blundell, T. L.; Mizuguchi, K. (2001). "FUGUE: Sequence-structure homology recognition using environment-specific substitution tables and structure-dependent gap penalties". Journal of Molecular Biology. 310 (1): 243–257. doi:10.1006/jmbi.2001.4762. PMID   11419950.
  30. ↑ Pandurangan, Arun Prasad; Ochoa-Montaño, Bernardo; Ascher, David B.; Blundell, Tom L. (3 July 2017). "SDM: a server for predicting effects of mutations on protein stability". Nucleic Acids Research. 45 (W1): W229–W235. doi:10.1093/nar/gkx439. ISSN   0305-1048. PMC   5793720 . PMID   28525590.
  31. ↑ Blundell TL, Johnson LN (1976), Protein Crystallography, Academic Press, ISBN   0121083500
  32. 1 2 Anon (1984). "EC/1984/03: Blundell, Sir Thomas Leon". royalsociety.org. London: Royal Society. Archived from the original on 16 January 2016. Retrieved 13 June 2014.
  33. ↑ "The Academy of Medical Sciences | Directory". Archived from the original on 1 October 2006. Retrieved 6 January 2009.
  34. ↑ "Past medals, awards and prize lectures". royalsociety.org. Retrieved 4 October 2017.
  35. ↑ T. Blundell awarded the eleventh Ewald Prize
  36. ↑ "Kirsty Young's castaway this week is the leading scientist Professor Sir Tom Blundell". Bbc.co.uk. Retrieved 3 July 2018.
  37. ↑ "Prof. Tom Blundell: A Personal History of Science and Ethics".
Academic offices
Preceded by Sir William Dunn Professor of Biochemistry, Cambridge University
1995–2009		Succeeded by
Government offices
Preceded by
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 CEO of the Biotechnology and Biological Sciences Research Council
1994–1996		Succeeded by
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