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]
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]
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]
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]
^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. PMID12923573. S2CID7010866.
^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. PMID9069283. S2CID4343341.
^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)
