Professor Sheena Radford

Profile

I joined the University of Leeds in 1995 as a Lecturer in the School of Biochemistry and Molecular Biology, progressing to Reader in 1998 and Professor in 2000. In 2009 I became the Deputy Director of the Astbury Centre for Structural Molecular Biology, and its Director in 2012 (until 2021). I became Astbury Professor of Biophysics in 2014 and Royal Society Research Professor in 2021.

Before coming to Leeds, I graduated with a BSc in Biochemistry at the University of Birmingham, completed my PhD in Biochemistry at the University of Cambridge with Professor R.N. Perham, FRS, and held various postdoctoral posts and a Royal Society University Research Fellowship at the Oxford Centre for Molecular Sciences.

I currently supervise ~25 PhD students and postdoctoral researchers in my laboratory. In total, more than 150 PhD students and postdocs have progressed successfully from the lab and have developed their own careers in academic research,  industrial posts, and other positions such as technical editing.

I have published more than 340 peer-reviewed papers and book chapters and have given more than 460 invited lectures at national and international conferences in countries including the UK, Germany, Denmark, USA, Australia, Japan, Sweden, Ireland, Belgium, Switzerland, Greece, Spain, Italy, France, The Netherlands, Portugal, Croatia, Israel, Austria, Canada, and Thailand, and online.

In the last five years I have served, or am serving on, 6 major research funding panels and 12 Scientific Advisory Boards at prestigious institutions. I have served on editorial boards for several journals, and am currently Associate Editor of the Journal of Molecular Biology and a Trustee of the Dementia Research Institute, UK.

I have been awarded several prizes and awards, including the 1996 Biochemical Society Colworth Medal, the 2005 Royal Society of Chemistry Astra-Zeneca prize in Proteins and Peptides, the 2009 Hites Award from the American Society for Mass Spectrometry (joint with Professor Alison Ashcroft), the Protein Society Carl Branden award in 2013, and the 2015 Rita and John Cornforth Award of the Royal Society of Chemistry (also jointly with Professor Alison Ashcroft). I was elected member of EMBO in 2007, member of Academia Europeae in 2020, Fellow of the Academy of Medical Sciences in 2010, the Royal Society in 2014, and made honorary member of the British Biophysical Society in 2014, a Fellow of the Biophysical Society in 2018, and an Officer of the Most Excellent Order of the British Empire (OBE) in 2020 for services to molecular biology research. In January 2021 I received a Royal Society Research Professorship and was elected a Fellow of the Royal Society of Biology. In 2022 I received the Doctorate honoris causa from the University of Liège, and in 2024 I became an International Member of the National Academy of Sciences (USA). Most recently, I was awarded the Biochemistry Society Centenary Award for 2025 to recognise a biochemist of distinction.

My research is focused on fundamental structural molecular biology, specifically in the measurement of the conformational dynamics of proteins and the elucidation of the role that these motions play in protein folding and misfolding of both water-soluble and membrane proteins. Using a wide range of biophysical methods and combining these with protein chemistry, molecular biology, chemical biology and structural biology, my research focus over the last 30 years has been the delineation of the mechanisms by which proteins fold or misfold; how dynamic excursions enable proteins to self-associate into amyloid fibrils - the complex macromolecular assemblies associated with some of the deadliest human diseases; and how proteins fold into the bacterial outer membranes of Gram-negative organisms.

My major research achievements to date have included the use of native mass spectrometry, NMR, and single molecule methods to characterise the intermediates in protein folding and in amyloid formation; to identify and delineate the mechanisms of action of small molecules able to interrupt protein aggregation; and the discovery of how and why different protein-protein interactions propagate amyloid formation whilst others inhibit assembly. In parallel, we have been using our biophysical toolkit of methods to understand how Gram-negative outer membrane proteins (OMPs) fold, how folding is supported by ATP-independent chaperones in the periplasm, and how the β-barrel assembly machinery (BAM) catalyses OMP folding and assembly into the bacterial cell envelope.

Links which may be of interest:

A lecture to celebrate being elected a Fellow of the Royal Society, 14 November 2014: Folding proteins – from Astbury to Amyloid and Ageing, https://www.youtube.com/watch?v=r1eK3DLCMcM 

Navigating a Career in Science (as a woman), 6 November 2017: presented at the University of Malta, https://www.youtube.com/watch?v=_lRQeGstRgo

        Proteostasis Consortium, USA, webinar, “Early Steps in Amyloid Assembly: The Achilles Heel of a Disease Mechanism,” 4 November 2020, 1 hour

https://www.facebook.com/watch/?v=3891791730834001

Cardiff Scientific Society Lecture – public lecture, online, “Folding a Protein: Nature’s Origami,” 9 February 2022, 55 minutes

http://sheena-radford-lab.uk/CSS%20Lecture%209%20090222.mp4

National Science Foundation (NSF) sponsored workshop on Neurodegeneration, Washington D.C., in person, “Progress Towards Cracking the Folding/Misfolding Code,” 20-21 June 2022, 16 minutes

https://www.youtube.com/watch?v=2uDZeGp0ZnA

Webinar to celebrate 60th anniversary of the Biochemistry Society Colworth Medal, to share experiences alongside a few other Colworth winners from across the decades, 14 September 2023, 1 hour

https://www.biochemistry.org/about-us/resources-and-videos/video-library/60-years-of-the-colworth-medal-a-view-across-the-decades-part-3/

  Biophysics Society Cell Press Webinar "Biophysics of Neurodegenerative Diseases"

“Combatting Amyloid Formation by Targeting Early Interactions in Assembly,” 9 March 2023, first 20 minutes, Biophysics of neurodegenerative diseases | Webinars | Resources | Nikon Europe B.V.

Proteostasis Consortium, USA, webinar, “How does an IDP aggregate into amyloid? Insights from structural approaches”  11 October 2023, 1 hour

Sheena Radford- 10/11/2023 (panopto.com)

Responsibilities

• Astbury Professor of Biophysics
• Royal Society Professor
• Group Leader of the Radford Laboratory

Research interests

Introduction

One of the most fascinating questions in biology is how proteins can fold and assemble into complex, functional entities given just the information provided by the amino acid sequence. A related, equally important facet of the same fundamental question is how protein misfolding can lead to protein aggregation, cellular dysfunction, and disease. These issues are the major focus of my research and are tackled using a broad range of techniques including protein chemistry, structural molecular biology, chemical biology, cell biology and biophysical methods.

Watch a lecture by Prof Radford discussing her work and celebrating her FRS award at https://www.youtube.com/watch?v=r1eK3DLCMcM

Current Major projects

• Mechanism(s) of protein misfolding and assembly into amyloid
• Outer Membrane Protein (OMP) folding – The role of chaperones and BAM
• Stabilising proteins of therapeutic interest against aggregation
• Method development (MS, NMR, single molecule, biophysical methods)

Detailed research programme: 

1. Mechanism(s) of protein misfolding and assembly into amyloid

How and why proteins aggregate into amyloid are important fundamental questions that have far-reaching biomedical importance. Focusing on the proteins (β2-microglobulin (dialysis related amyloidosis)); amylin (type II diabetes); α-synuclein (Parkinson’s) and Aβ (Alzheimer’s), work in the group aims to map the structural mechanism of amyloid formation and to develop reagents to control aggregation in vitro and in vivo. Recent highlights include structure determination of oligomers (NMR, Karamanos (2019) eLife) and fibrils (cryoEM, (with Ranson) (Gallardo (2020) Nature Struct. Mol. Biol.); Wilkinson (2023) Nature Comms.), discovery of small molecules that modulate amyloid formation (Cawood (2020) JACS, Xu (2022) Nature Comms.); and demonstration that early protein-protein interactions in amyloid formation are specific and can be targeted to arrest assembly in vitro and in vivo (Doherty (2020) Nature Struct. Mol. Biol., Ulamec Nature Comms. (2022), Guthertz PNAS (2022)). We have also recently shown that amyloid fibrils structures changes with time (Wilkinson Cell (2023)) and, with Rene Frank and Neil Ranson, have provided the first insights into amyloid in the mouse and human brain of Alzheimer’s patients (Leistner Nat Comms (2023) and  Gilbert Nature (2024)).

2.  Outer membrane protein (OMP) – The role of chaperones and BAM

How OMPs fold and assemble into the asymmetric outer membrane (OM) of Gram-negative bacteria is a second research theme in our lab. In a collaborative multidisciplinary team (with David Brockwell, Neil Ranson, Roman Tuma and Ian Collinson (Bristol)) we are investigating how OMPs cross the inner-membrane via SecYEG (Fessl (2018) eLife); traverse the periplasm aided by chaperones (Skp/SurA) (Calabrese (2020) Nature Comms), fold into membranes in vitro (Vorobieva (2021) Science) and in vivo catalysed by the essential beta-barrel membrane machinery (BAM) (Iadanza (2020) Comms. Biol., Schiffrin (2022) Comms. Biol.). Building on these insights we are currently exploring the dynamic motions of BAM during catalysis and how this can be harnessed to generate new antibacterial agents against Gram-negative pathogens (White (2021) Nature Comms.). Most recently, we have used smFRET and NMR methods to map the binding of client OMPs to their chaperone, SurA (Schiffrin Nat. Comms (2024)) and used cryoEM, smFRET and proteomics to reveal a catalytic cycle of SurA caught in the act of delivering OMPs to BAM (Fenn Nat Comms. (2024)).

3. Stabilising proteins of therapeutic interest against aggregation 

We are also exploiting our knowledge of protein folding/aggregation to practical benefit by screening amyloidogenic proteins, as well as proteins of interest to biopharma, for hotspots that cause aggregation. By coupling aggregation to bacterial growth using a tripartite β-lactamase fusion construct we have discovered small molecules that prevent aggregation of amyloidogenic proteins (Saunders (2016) Nature Chem. Biol.). With David Brockwell and our collaborators in AstraZeneca, we recently combined the assay with directed evolution to enhance the resilience of biopharmaceutically-relevant antibodies to aggregation (Ebo (2020) Nature Comms.). Finally, in collaboration with David Brockwell and Nik Kapur (Mechanical Engineering, Leeds), we are examining how flow fields enhance, or cause, aggregation by flow-induced protein deformations (Dobson (2017) PNAS, Willis (2020) Eng. Rep. Willis J. Pharm. Sci. (2024)).

4. Method development (MS, NMR, single molecule, biophysical methods) 

Major developments in methods and instrumentation have played a key role in increasing in our understanding of protein folding and aggregation. Future developments in these fields will also require innovative approaches that cross the boundaries between disciplines. We have been involved in many exciting collaborations to fulfil this aim. With Professors Alison Ashcroft (now emeritus) and Frank Sobott we have developed and expanded our arsenal of methods to interrogate protein folding, protein-protein interactions, and protein complexes, including MS methods (HDX-MS and fast photochemical oxidation of proteins (FPOP-MS)) (Cornwell (2019) Analyt. Chem., Cornwell (2021) J. Am. Soc. MS.); ion mobility MS to determine the effect of ligand binding on amyloidogenic monomers and oligomers (Byrd (2023) J. Am. Soc. MS.) and, with Andrew Wilson (Chemistry) we have developed rapid crosslinking to map protein-chaperone interactions (Horne (2018) Angewandte Chemie, Calabrese (2020) Nature Comms.). Developments in NMR methods remain a mainstay of our laboratory activities (Karamanos (2022) Frontiers Neurosci.). In collaboration with David Brockwell and George Heath we are involved in exciting developments in the use of the AFM for measurements of protein unfolding and protein binding (Ulamec (2021) Nature Comms.) and with Paolo Actis (Mechanical Engineering) in the development of nanopores for the manipulation and identification of protein assemblies (Chau (2020) Nanoletters, Chau (2022) ACS Nano, Chalmers Nat Comms. (2024)).

More information about all these projects can be found on the websites of our collaborators’ Astbury web pages.

For further details about the Radford laboratory, people involved, molecular images and available opportunities, please see http://sheena-radford-lab.uk

• Breaking the Barrier: Mapping protein interactions in the bacterial outer membrane as targets for new antimicrobials
• Delivery and clearance of outer membrane proteins to the bacterial outer membrane
• EMBeDs: Ensuring Manufacturability of next-generation Biopharmaceuticals by Design
• Molecular grammar of SurA-client interactions in the periplasm of gram-negative bacteria
• Seeing the Unseeable: How Does Protein Dynamic Disorder Shape Biology
• State of the art electron detection for cyoEM at the Astbury Biostructure Laboratories

Qualifications

• BSc, Birmingham, 1984
• PhD, Cambridge, 1987

Professional memberships

• 2024, Int'l Member of the NAS (USA) & Biochemistry Society Centenary Award for 2025
• 2020, Member of the Academia Europaea, Hon Doctorate, Liège, 2022
• 2021, RS Research Professorship and Fellow of the RS of Biology
• 2020, OBE and Member of the Academia Europaea, 2020
• 2019, Honorary Fellow, St John’s College, Cambridge
• 2017, Fellow of the Biophysical Society for leadership in protein biophysics
• 2014, FRS and Hon Member British Biophysical Society
• 2010, Fellow of Academy of Medical Sciences
• 2007, Fellow of EMBO (European Molecular Biology Organization)
• 2003, Fellow of the Royal Society of Chemistry; also Member of the Biochemical Society and the Protein Society

Student education

I have taught Biochemistry at both undergraduate and postgraduate levels at the University of Leeds since 1995, been an active tutor and supervisor of students at all levels, and, until fairly recently, taught basic mechanisms and concepts in protein folding, and contributed to Advanced Topic Units for final year students. I have been involved with our laboratory’s hosting of students for their final year research projects (Biochemistry and Biological Sciences) for both BSc and MBiol schemes.

Research groups and institutes

• Structural Biology

Current postgraduate researchers

• Jim Horne