Sheena RADFORD
Director of the prestigious Astbury Centre for Structural Molecular Biology, Sheena Radford has greatly contributed to the understanding of the mechanisms involved in protein folding and self-assembly.
A lecture by Ms Sheena RADFORD entitled "Folding a Protein: Nature's Origami" will take place on Friday 18 March 2022 at 11:00 am in the Amphitheatres of Europe, Room R52, building B4.
Sheena Radford studied biochemistry at the University of Birmingham, before obtaining a DPhil from the University of Cambridge (UK), under the supervision of Richard N. Perham, in 1987. She then pursued post-doctoral research at the Oxford Centre for Molecular Sciences (University of Oxford, UK, 1988-1995), where she collaborated closely with Professor Chris M. Dobson (himself an honorary doctor of ULiège, since 2007, deceased on 8th September 2021). The aim of their work was to solve the problem of protein folding. This process is particularly remarkable in that, within a cell, a newly synthesised protein at the level of the ribosomes can, in a few seconds or less, go from a totally disorganised structure to a compact, specific and biologically active conformation, as observed using structural methods. At that time, it was generally accepted that the structure of a protein was determined by its amino acid sequence; how this was possible, however, remained largely unknown. And the paradox, as formulated by Cyrus Levinthal (1968), made this process even more mysterious. A simple calculation estimated that the time required for a polypeptide chain to explore all possible conformations in order to find the correct (usually most stable) one was comparable to the age of the universe. Sheena Radford and Chris Dobson's research led them to progressively integrate new techniques (e.g. fluorescence, circular dichroism, mass spectrometry, NMR), in order to be able to describe the extremely complex phenomena related to protein folding. In particular, their research on lysozyme enabled the detailed description, at the molecular level, of parallel folding pathways and partially structured folding intermediates, thus shedding light on a mechanism of unsuspected complexity for a protein of such a small size (129 residues).
In 1995, Sheena Radford became a lecturer at the University of Leeds, and was appointed Reader and then Professor of Structural Molecular Biology, in 1995 and 2000 respectively. Since 2014, she has held the position of Astbury Professor of Biophysics. On the research side, she is part of the prestigious Astbury Centre for Structural Molecular Biology, of which she has been Director since 2012.
Since her early days as a research scientist, Sheena Radford has focused her work in the field of fundamental structural molecular biology, in particular concentrating on measuring the conformational dynamics of proteins and highlighting the role that these movements play in protein folding and misfolding. Using a wide range of biochemical and biophysical methods, in combination with approaches from protein chemistry and molecular biology, her research over the past 30 years has focused on describing the mechanisms by which proteins fold correctly or incorrectly. In particular, it has provided a series of major insights into the phenomena of protein self-assembly into huge macromolecular complexes (i.e. amyloid fibres), some of which are associated with fatal diseases (e.g. Parkinson's, Alzheimer's) that are a growing public health problem.
From a more technical point of view, Sheena Radford has used, developed and exploited the use of various so-called "native" mass spectrometry (MS) methods, such as MS-coupled hydrogen exchange, FPOPMS (Fast Photochemical Oxidation of Proteins) and ion mobility. These methods, used in combination with sophisticated modelling techniques, have enabled the analysis of complex folding and self-assembly kinetics. Structural information on intermediate species was obtained using the full power of modern NMR methods for the analysis of protein conformation, including some partially folded, unfolded, rare and dynamic forms. In parallel, Sheena Radford has also used atomic force microscopy for single-molecule observation, which has allowed her to characterise folding intermediates in other ways, including during amyloid fibre formation. Recently, Sheena Radford has also developed an interest in membrane protein folding. Her work includes the use of cryo-electron microscopy, using the state-of-the-art equipment available at the Astbury Centre, for which she was instrumental in obtaining funding.
Throughout her remarkable career, Sheena Radford has been committed to a multidisciplinary approach to understanding the properties of proteins. Her laboratory has used and developed many of the above techniques and she has become one of the most respected scientists of our time. Her research has greatly contributed to the understanding of the mechanisms involved in protein folding and self-assembly. Her work earned her a Fellowship of the Royal Society (FRS) in 2014.
Sheena Radford has published over 290 scientific papers in leading journals, including over 20 in Nature, Nature Structural (and Molecular) Biology, Nature Chemical Biology and Nature Chemistry, three in Cell and one in Science. Sheena Radford has been honoured with a number of international awards, including The Biochemical Society - Colworth Medal (1996), The Royal Society of Chemistry Astra-Zeneca prize: Proteins and Peptides (2005), Hites Award, American Society for Mass Spectrometry (jointly with Professor Alison Ashcroft, 2009), The Protein Society - Carl Branden Award (2013), The Rita and John Cornforth Award of the Royal Society of Chemistry (jointly with Professor Alison Ashcroft, 2015), The Election to the 2018 Fellow of the Biophysical Society for 'Leadership in protein biophysics' (2017), and The Election to Honorary Fellowship of St John's College, Cambridge (2019).
On numerous occasions, Sheena Radford has been invited to present her research at international conferences and institutional visits. These include the Prize Lecture: Colworth Medal London, UK (1996), Plenary Lecture: British & French Electrophoresis Society Lecture, Paris, France (1999), Plenary Lecture: 2nd IMB Symposium, Jena, Germany (2003), Plenary Lecture: Macromolecular Dynamics and Interactions, Melbourne, Australia (2005), The Wills Lecture: Queen Mary College, London, UK (2007), Plenary Lecture: Protein Misfolding & Neurological Disorders, Dunk Island, Australia (2007), Dean's Lecture: Ben Gurion University, Israel (2010), Plenary Lecture: Jacques Monod Conference, Protein Misfolding & Aggregation, France (2010), Plenary Lecture: ComBio Conference, Canberra, Australia (2011), Award Lecture: Carl Branden Award, Protein Society, Boston, USA (2013), Albright Lecture, Philadelphia, USA (2013), Welch Foundation Lecture: Large Problems in Life Chemistry, Texas (2013), Plenary Lecture: Biophysics Society Annual Symposium in Taiwan (2014), Keynote Lecture: FASEB Folding in the Cell, Vermont (2016), Keynote Lecture: FASEB Protein Aggregation in Health & Disease, Montana (2017), Keynote speaker: British Biophysical Society IUPAB congress Edinburgh (2017), BPE/FEMS conference on 'Bacterial protein secretion', Leuven, Belgium (2018), FASEB Summer Research Conference on Protein Aggregation, Colorado (2019) and GRC on Membrane Protein Folding Easton, Massachusetts (2019).
