Professor Sheena Radford OBE, FMedSci, FRS

An image showing a protein structure in ribbon diagram of beta-2-microglobulin on top of a negative stain electron micrograph of amyloid fibrils formed from the protein.


One of the most fascinating questions in biology is how proteins are able to 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. Go to

Current major projects

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

Detailed research programme

Mechanism(s) of protein misfolding and assembly into amyloid

Image of questions in the amyloid field shown as a zigsaw. Highlights aggregation kinetics, mass spectrometry, solid state NMR, cryoEm, cryoET, in vivo aggregation and pathology.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) (Iadanza (2018) Nature Comms.)); Gallardo (2020) Nature Struct. Mol. Biol.)); discovery of small molecules that modulate amyloid formation (ESI-MS (Young (2015) Nature Chem.), and covalent tethering/chemical biology (Cawood (2020) JACS)); 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.).

Outer Membrane Protein (OMP) folding – The role of chaperones & BAM

How OMPs fold and assemble into the asymmetric outer-membrane (OM) of Gram-negativeSchamtic showing the passage of OMPs from synthesis on the ribosome to the outer membrane and involving the chaperones SurA and Skp and the BAM complex. 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) (Schiffrin (2016) Nature Struct. Mol. Biol., Calabrese (2020) Nature Comms)), fold into membranes in vitro (Husymans, (2010) PNAS, Vorobieva (2021) Science) and in vivo catalysed by the essential b-barrel membrane machinery (BAM) (Iadanza (2016) Nature Comms, Schiffrin (2017) JMB, Iadanza (2020) 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.

Stabilising proteins of therapeutic interest against aggregation

A diagram showing the insert of a protein of interest into the loops of beta-lactamase ahd how aggregation would then result in loss of antibiotic resistance in bacteria.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.).

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

A diagram showing and outer membrane protein and highlighting residues that are oxidised and hence solvent exposed.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 Alison Ashcroft (now emeritus), Frank Sobott and Andrew Wilson 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)) to map transient interactions Cornwell (2019) Analyt. Chem., Cornwell (2021) J. Am. Soc. MS,); ion mobility MS to map oligomers formed during aggregation (Young (2017) Chem. Sci.) and ligand binding to amyloidogenic monomers and oligomers (Young (2016) Nature Chem.) and ultrarapid 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, whilst, in collaboration with David Brockwell we are involved in exciting developments in the use of the AFM and flow devices for measurements of protein unfolding and protein binding. More information about 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