Sheena Radford

Last updated

Sheena Radford

FRS FMedSci
Born
Sheena Elizabeth Radford
Alma mater
SpouseAlan Berry [1]
Awards
Scientific career
Fields
Institutions
Thesis Domains and conformational flexibility in the catalytic mechanism of the 2-oxo acid dehydrogenase complexes  (1987)
Website astbury.leeds.ac.uk/bmbsgi10

Sheena Elizabeth Radford OBE FRS [2] FMedSci [3] is a British biophysicist, and Astbury Professor of Biophysics in the Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology at the University of Leeds. [1] [4] [5] [6] Radford is the Associate Editor of the Journal of Molecular Biology. [7]

Contents

Education

Radford received her BSc in Biochemistry at the University of Birmingham [7] in 1984, [8] and her PhD in Biochemistry at the University of Cambridge in 1987. [1] [9] [10] Radford completed a post-doctoral fellowship at the University of Oxford. [8]

Career and research

Radford worked as a Lecturer in Biochemistry and Molecular Biology at the University of Leeds in 1995, progressing to Reader in 1998 and Professor in 2000. She became the Deputy Director of the Astbury Centre for Structural Molecular Biology in 2009 then Director in 2012. [7] Radford's research [11] investigates protein folding, protein aggregation and amyloid disease. [12] [13] [14] [15] [16] [17] [18] Her multi-disciplinary research focuses include such disciplines as biochemistry, chemistry and medicine.

One major research focus is the role of protein misfolding in the onset of amyloidogenic diseases, including dialysis-related amyloidosis, Alzheimer's and Type II diabetes. This has been done with the use of native mass spectrometry, NMR and single molecule methods to characterize intermediates of protein folding and in amyloid formation. [7] A second research focus is on the folding of outer membrane proteins of Gram-negative organisms. Understanding the mechanics of how these proteins fold will help derive new antibiotics. [19]

In 2016, [20] Radford received an Investigator Award in Science for Protein-protein interactions in the early stages of amyloid assembly mechanisms.

In 2020, [21] a collaboration between scientists at the University of Leeds and AstraZeneca led to the development of a technique that, "allows fragments of antibodies to be screened for susceptibility to aggregation caused by structure disruption much earlier in the drug discovery process." [21] Protein sequences hosted in bacterial cells that have shown resistance are harvested and their genes sequenced. Radford said that sequences will be uploaded to a database where advances in machine learning will eventually be able to identify patterns in protein sequences that can be scaled up for pharmaceutical production without needing any experiments.

In 2021, [22] an advance in biomolecular design was the creation of new proteins that were shown in the lab to spontaneously fold into their intended structures and embed into lipid membranes as reported in Science with lead author Anastassia Vorobieva. [23] Bacteria are encased in an outer membrane. Proteins in this outer membrane facilitate transport with the outside world. These proteins share a similar nanoscale structure, a transmembrane beta-barrel, through which other molecules can pass. Vorobieva and colleagues used molecular design software to draft possible structures. Radford's team tested whether these improved proteins would embed into artificial lipid membranes, finding that they could so efficiently without any accessory proteins. Radford said, "These designed proteins are interesting from a basic science perspective because they have no evolutionary history. By studying them, we can discover some of the essential features that enable transmembrane beta-barrel proteins to fold into a membrane." [22]

Awards and honours

Radford received the first Ron Hites award with Alison E. Ashcroft, and their coauthors for their paper, "Monitoring Co-populated Conformational States during Protein Folding Events using Electrospray Ionization-Ion Mobility Spectrometry-Mass Spectrometry" written by David P. Smith, Kevin Giles, Robert H. Bateman, Sheena E. Radford, and Alison E. Ashcroft. [25]

"The Ron Hites Award recognizes a high quality presentation of outstanding original research. Selection is based on a paper's innovative aspects, technical quality, likely stimulation of future research, likely impact on future applications, and quality of presentation. The Award is named in honor of Professor Ronald A. Hites of Indiana University, who led the creation of JASMS in 1988 while president of ASMS." [25]

Radford was elected a Fellow of the Royal Society (FRS) in 2014; her nomination reads:

Sheena Radford is internationally distinguished for her seminal contributions to understanding how the dynamical properties of proteins enable them to fold and function biologically, or to misfold and cause degenerative diseases. She has used sophisticated experimental techniques to characterise protein folding pathways in exquisite detail, in particular demonstrating that non-native as well as native-like interactions can play key roles in stabilising partially folded intermediate states. She has built on these findings to define key steps in the aberrant self-assembly of misfolded proteins into amyloid fibrils, particularly in dialysis related amyloidosis, and to relate these molecular processes to pathogenesis. [2]

Radford was elected a Fellow of the Academy of Medical Sciences (FMedSci) in 2010. Her nomination reads:

Sheena Radford is Professor of Structural Molecular Biology at the University of Leeds. Her achievements have involved the innovative application of biophysical techniques to protein folding problems. Her early work in Oxford on hen lysozyme was the foundation for current views that proteins fold on complex multidimensional landscapes, commonly known as folding funnels. She has extended her research to encompass misfolding and disease and has also developed new physical methods to study ultrafast processes. Sheena's work on dialysis-dependent amyloidosis has shown that protein unfolding of beta-2-microglobulin is a key step in fibril formation. [3]

Radford is a member of Faculty of 1000. [26]

Radford was appointed Officer of the Order of the British Empire (OBE) in the 2020 Birthday Honours for services to molecular biology research. [27]

Related Research Articles

<span class="mw-page-title-main">Structural biology</span> Study of molecular structures in biology

Structural biology, as defined by the Journal of Structural Biology, deals with structural analysis of living material at every level of organization. Early structural biologists throughout the 19th and early 20th centuries were primarily only able to study structures to the limit of the naked eye's visual acuity and through magnifying glasses and light microscopes.

<span class="mw-page-title-main">Protein folding</span> Change of a linear protein chain to a 3D structure

Protein folding is the physical process by which a protein, after synthesis by a ribosome as a linear chain of amino acids, changes from an unstable random coil into a more ordered three-dimensional structure. This structure permits the protein to become biologically functional.

<span class="mw-page-title-main">Amyloid</span> Insoluble protein aggregate with a fibrillar morphology

Amyloids are aggregates of proteins characterised by a fibrillar morphology of typically 7–13 nm in diameter, a β-sheet secondary structure and ability to be stained by particular dyes, such as Congo red. In the human body, amyloids have been linked to the development of various diseases. Pathogenic amyloids form when previously healthy proteins lose their normal structure and physiological functions (misfolding) and form fibrous deposits within and around cells. These protein misfolding and deposition processes disrupt the healthy function of tissues and organs.

<span class="mw-page-title-main">Amyloid beta</span> Group of peptides

Amyloid beta denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid-beta precursor protein (APP), which is cleaved by beta secretase and gamma secretase to yield Aβ in a cholesterol-dependent process and substrate presentation. Aβ molecules can aggregate to form flexible soluble oligomers which may exist in several forms. It is now believed that certain misfolded oligomers can induce other Aβ molecules to also take the misfolded oligomeric form, leading to a chain reaction akin to a prion infection. The oligomers are toxic to nerve cells. The other protein implicated in Alzheimer's disease, tau protein, also forms such prion-like misfolded oligomers, and there is some evidence that misfolded Aβ can induce tau to misfold.

<span class="mw-page-title-main">Richard Henderson (biologist)</span> British biologist

Richard Henderson is a British molecular biologist and biophysicist and pioneer in the field of electron microscopy of biological molecules. Henderson shared the Nobel Prize in Chemistry in 2017 with Jacques Dubochet and Joachim Frank."Thanks to his work, we can look at individual atoms of living nature, thanks to cryo-electron microscopes we can see details without destroying samples, and for this he won the Nobel Prize in Chemistry."

Sir John Anthony Hardy is a human geneticist and molecular biologist at the Reta Lila Weston Institute of Neurological Studies at University College London with research interests in neurological diseases.

<span class="mw-page-title-main">Alpha sheet</span> Secondary protein structure

Alpha sheet is an atypical secondary structure in proteins, first proposed by Linus Pauling and Robert Corey in 1951. The hydrogen bonding pattern in an alpha sheet is similar to that of a beta sheet, but the orientation of the carbonyl and amino groups in the peptide bond units is distinctive; in a single strand, all the carbonyl groups are oriented in the same direction on one side of the pleat, and all the amino groups are oriented in the same direction on the opposite side of the sheet. Thus the alpha sheet accumulates an inherent separation of electrostatic charge, with one edge of the sheet exposing negatively charged carbonyl groups and the opposite edge exposing positively charged amino groups. Unlike the alpha helix and beta sheet, the alpha sheet configuration does not require all component amino acid residues to lie within a single region of dihedral angles; instead, the alpha sheet contains residues of alternating dihedrals in the traditional right-handed (αR) and left-handed (αL) helical regions of Ramachandran space. Although the alpha sheet is only rarely observed in natural protein structures, it has been speculated to play a role in amyloid disease and it was found to be a stable form for amyloidogenic proteins in molecular dynamics simulations. Alpha sheets have also been observed in X-ray crystallography structures of designed peptides.

Jeffery W. Kelly is an American businessman and chemist who is on the faculty of the Scripps Research Institute in La Jolla, California.

The familial amyloid neuropathies are a rare group of autosomal dominant diseases wherein the autonomic nervous system and/or other nerves are compromised by protein aggregation and/or amyloid fibril formation.

<span class="mw-page-title-main">Protein aggregation</span> Accumulation of clumps of misfolded or disordered proteins

In molecular biology, protein aggregation is a phenomenon in which intrinsically-disordered or mis-folded proteins aggregate either intra- or extracellularly. Protein aggregates have been implicated in a wide variety of diseases known as amyloidoses, including ALS, Alzheimer's, Parkinson's and prion disease.

<span class="mw-page-title-main">Carol V. Robinson</span> British chemist and professor

Dame Carol Vivien Robinson, is a British chemist and former president of the Royal Society of Chemistry (2018–2020). She was a Royal Society Research Professor and is the Dr Lee's Professor of Physical and Theoretical Chemistry, and a professorial fellow at Exeter College, University of Oxford. She is the first director of the Kavli Institution for Nanoscience Discovery, University of Oxford, and she was previously professor of mass spectrometry at the chemistry department of the University of Cambridge.

Sir Mark Brian Pepys is a South African-born British academic of medicine. He was until 2011 Professor of Medicine at University College London and Head of Medicine at the Hampstead Campus and the Royal Free Hospital.

<span class="mw-page-title-main">Chris Dobson</span> British chemist (1949–2019)

Sir Christopher Martin Dobson was a British chemist, who was the John Humphrey Plummer Professor of Chemical and Structural Biology in the Department of Chemistry at the University of Cambridge, and Master of St John's College, Cambridge.

Gabriel Waksman FMedSci, FRS, is Courtauld professor of biochemistry and molecular biology at University College London (UCL), and professor of structural and molecular biology at Birkbeck College, University of London. He is the director of the Institute of Structural and Molecular Biology (ISMB) at UCL and Birkbeck, head of the Department of Structural and Molecular Biology at UCL, and head of the Department of Biological Sciences at Birkbeck.

<span class="mw-page-title-main">Jane Clarke (scientist)</span> English biochemist and academic

Jane Clarke is an English biochemist and academic. Since October 2017, she has served as President of Wolfson College, Cambridge. She is also Professor of Molecular Biophysics, a Wellcome Trust Senior Research Fellow in the Department of Chemistry at the University of Cambridge. She was previously a Fellow of Trinity Hall, Cambridge. In 2023, she was elected to the National Academy of Sciences.

<span class="mw-page-title-main">Michele Vendruscolo</span> Italian British physicist

Michele Vendruscolo is an Italian British physicist working in the UK, noted for his theoretical and experimental work on protein folding, misfolding and aggregation.

<span class="mw-page-title-main">Fabrizio Chiti</span> Italian biochemist

Fabrizio Chiti is an Italian biochemist noted for his work on Protein aggregation and amyloid.

Alison E Ashcroft is a British chemist and Emeritus Professor of Biomolecular Mass Spectrometry at the University of Leeds. Her work is focused on method development in mass spectrometry to study protein folding and protein aggregation in relation to diseases.

Jean Baum is an American chemist. She is the distinguished professor of chemistry and chemical biology at Rutgers University, where she is also vice dean for research and graduate education in the school of arts and sciences, and also vice chair of the department of chemistry and chemical biology. Her research investigates protein–protein interaction and protein aggregation using nuclear magnetic resonance spectroscopy (NMR) and other biochemical and biophysical techniques. She serves as treasurer for the Protein Society.

References

  1. 1 2 3 4 5 Anon (2017). "Radford, Prof. Sheena Elizabeth" . Who's Who (online Oxford University Press  ed.). Oxford: A & C Black. doi:10.1093/ww/9780199540884.013.U281947.(Subscription or UK public library membership required.)
  2. 1 2 Anon (2014). "Professor Sheena Radford FMedSci FRS". London: royalsociety.org. Archived from the original on 2 May 2014.
  3. 1 2 Anon (2010). "Professor Sheena Radford FRS FMedSci". acmedsci.ac.uk. London: Academy of Medical Sciences. Archived from the original on 6 October 2014.
  4. ↑ Sheena Radford's publications indexed by the Scopus bibliographic database. (subscription required)
  5. ↑ Folding proteins – from Astbury to Amyloid and Ageing on YouTube
  6. ↑ Astbury Centre for Structural Molecular Biology on YouTube
  7. 1 2 3 4 biologicalsciences. "Professor Sheena Radford | Faculty of Biological Sciences | University of Leeds". biologicalsciences.leeds.ac.uk. Retrieved 14 March 2021.
  8. 1 2 "Sheena E Radford | Faculty Member | Faculty Opinions". facultyopinions.com. Retrieved 14 March 2021.
  9. ↑ Radford, Sheena Elizabeth (1987). Domains and conformational flexibility in the catalytic mechanism of the 2-oxo acid dehydrogenase complexes. cam.ac.uk (PhD thesis). University of Cambridge. OCLC   53606268. EThOS   uk.bl.ethos.236036.
  10. ↑ "Prof Sheena Radford | Faculty of Biological Sciences". University of Leeds. Retrieved 10 June 2014.
  11. ↑ Sheena Radford ORCID   0000-0002-3079-8039
  12. ↑ Booth, D. R.; Sunde, M; Bellotti, V; Robinson, C. V.; Hutchinson, W. L.; Fraser, P. E.; Hawkins, P. N.; Dobson, C. M.; Radford, S. E.; Blake, C. C.; Pepys, M. B. (1997). "Instability, unfolding and aggregation of human lysozyme variants underlying amyloid fibrillogenesis". Nature . 385 (6619): 787–93. Bibcode:1997Natur.385..787B. doi:10.1038/385787a0. PMID   9039909. S2CID   4347837.
  13. ↑ Radford, S. E.; Dobson, C. M.; Evans, P. A. (1992). "The folding of hen lysozyme involves partially structured intermediates and multiple pathways". Nature. 358 (6384): 302–7. Bibcode:1992Natur.358..302R. doi:10.1038/358302a0. PMID   1641003. S2CID   4353275.
  14. ↑ Linse, S.; Cabaleiro-Lago, C.; Xue, W. -F.; Lynch, I.; Lindman, S.; Thulin, E.; Radford, S. E.; Dawson, K. A. (2007). "Nucleation of protein fibrillation by nanoparticles". Proceedings of the National Academy of Sciences . 104 (21): 8691–8696. Bibcode:2007PNAS..104.8691L. doi: 10.1073/pnas.0701250104 . PMC   1866183 . PMID   17485668.
  15. ↑ Brockwell, D. J.; Paci, E.; Zinober, R. C.; Beddard, G. S.; Olmsted, P. D.; Smith, D. A.; Perham, R. N.; Radford, S. E. (2003). "Pulling geometry defines the mechanical resistance of a β-sheet protein". Nature Structural Biology . 10 (9): 731–7. doi:10.1038/nsb968. PMID   12923573. S2CID   7010866.
  16. ↑ Dobson, C. M.; Evans, P. A.; Radford, S. E. (1994). "Understanding how proteins fold: The lysozyme story so far". Trends in Biochemical Sciences . 19 (1): 31–7. doi:10.1016/0968-0004(94)90171-6. PMID   8140619.
  17. ↑ Miranker, A; Robinson, C. V.; Radford, S. E.; Aplin, R. T.; Dobson, C. M. (1993). "Detection of transient protein folding populations by mass spectrometry". Science . 262 (5135): 896–900. Bibcode:1993Sci...262..896M. doi:10.1126/science.8235611. PMID   8235611.
  18. ↑ Aggeli, A.; Bell, M.; Boden, N.; Keen, J. N.; Knowles, P. F.; McLeish, T. C. B.; Pitkeathly, M.; Radford, S. E. (1997). "Responsive gels formed by the spontaneous self-assembly of peptides into polymeric β-sheet tapes". Nature. 386 (6622): 259–62. Bibcode:1997Natur.386..259A. doi:10.1038/386259a0. PMID   9069283. S2CID   4343341.
  19. ↑ Academy, 4Ward North Clinical PhD. "Professor Sheena Radford". 4Ward North Clinical PhD Academy. Retrieved 14 March 2021.{{cite web}}: CS1 maint: numeric names: authors list (link)
  20. ↑ "Protein-protein interactions in the early stages of amyloid assembly mechanisms". Wellcome. Retrieved 14 March 2021.
  21. 1 2 "'Directing' evolution to identify potential drugs earlier in discovery". ScienceDaily. Retrieved 14 March 2021.
  22. 1 2 "Pore-like proteins designed from scratch". EurekAlert!. Retrieved 14 March 2021.
  23. ↑ "Pore-like proteins designed from scratch". ScienceDaily. Retrieved 14 March 2021.
  24. ↑ "IFCC honors Sacks; Radford receives OBE; remembering Schonbaum". www.asbmb.org. Retrieved 14 March 2021.
  25. 1 2 Gross, Michael L. (November 2009). "First Ron Hites Award goes to Alison E. Ashcroft, Sheena Radford, and Coauthors". Journal of the American Society for Mass Spectrometry. 20 (11): I1–I3. doi: 10.1016/j.jasms.2009.08.005 . PMID   19744864.
  26. ↑ "Sheena Radford: Section Head in Protein Chemistry & Proteomics". f1000.com. Retrieved 10 June 2014.
  27. ↑ "No. 63135". The London Gazette (Supplement). 10 October 2020. p. B14.
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