Radford Research Group

Group Leader - Prof. Sheena E. Radford
Research Interests: Protein Folding and Misfolding.

BSc in Biochemistry, University of Birmingham; PhD Biochemistry, University of Cambridge; Royal Society University Research Fellow (Protein Folding) in the Oxford Centre for Molecular Sciences; University Lecturer in the School of Biochemistry & Molecular Biology, University of Leeds; Reader in Structural Molecular Biology, University of Leeds; Professor of Structural Molecular Biology, University of Leeds. Contact details: Astbury Centre of Structural Molecular Biology, Garstang Building, University of Leeds, Leeds, LS2 9JT Tel: 0113 343 3170; FAX: 0113 343 3167; email: s.e.radford@leeds.ac.uk Alternatively you may contact my secretary Sue Wright Tel: 0113 343 7036 or email susan.c.wright@leeds.ac.uk

The group - Summer 2008	The group - Sept 2009

Current Group Members

Susan Wright Sue organises everything in the group and keeps everything running smoothly. She is happy to help any one interested in any group activities. Please contact her using the details given above.
Eva Petrik Eva is in the third year of our Wellcome Trust 4-year PhD programme having joined the scheme from Hungary. She is investigating the mechanism of light chain amyloidosis using the incorporation of non-natural amino acids to unpick the mechanism of amyloid formation.
Lucy Woods Lucy is a graduate in Chemistry from the University of Leeds. She is currently funded by the BBSRC to work on a project to develop mass spectrometry methods to investigate protein-protein interactions in amyloidosis. She is jointly supervised with Dr Alison Ashcroft.
Keith Ainley Keith is the group technician shared between the Radford, Berry and Brockwell research groups. Keith is skilled in microbiology and grows large cultures for us, as well as maintaining our stocks of bacteria. He helps with protein purifications and maintains all our instrumentation. In summary, Keith keeps the lab running smoothly!
Dr Geoff Platt Geoff joined the group in 2003. He brings kinetics and NMR experience to the group and is working on the use of NMR methods to study the conformational properties of partially folded states of beta-2 microglobulin
Dr Wei Feng Xue Wei Feng joined the group in 2006 having completed his PhD in Lund, Sweden. He brings expertise in protein-protein interactions using a wide variety of biophysical methods. His project focusses on structural elucidation of the early stages of nucleated fibril growth.
Timo Eichner Timo joined the group in 2006 having completed his degree in Germany and having worked in the USA. He is doing his PhD in protein folding and self-assembly of beta-2-microglobulin using a wide range of biophysical methods. He is funded by a University research scholarship.
Alice Bartlett Alice is a final year PhD student. She joined the group having completed a degree in Biochemistry at the University of Bristol. She is using ultra-rapid mixing, stopped-flow and single molecule fluorescence to unravel new details about the mechanism of protein folding. She is also studying the mechanism of membrane protein folding.
Dr Gareth Morgan Gareth joined the group in July 2007 having completed his PhD in Sheffield. He is combining his expertise in NMR with biophysical analysis of proteins and is working on a new project in collaboration with Prof Jim Bardwell (University of Michegan) to elucidate how folding and function compete in the evolution of new proteins.
Dr Maarten Engel Maarten is an EMBO Fellow who joined the group in October 2007. He brings his expertise in IAPP aggregation to the group and is using single-molecule methods combined with other analyses to determine how this small peptide aggregates to form amyloid associated with diabetes.
Dr Carol Ladner Carol joined the beta-2-m amyloid team in 2007 having completed her PhD studies at the University of Calgary, Canada. She brings expertise in chemical modification and spectroscopy to the group and is using these to determine the structure of amyloid fibrils.
Karine Deville Karine is in the final year of our Wellcome Trust 4-year PhD programme. Jointly supervised by Steve Baldwin, and in collaboration with Ian Collinson (Bristol), she is using single-molecule methods to examine dynamics during SecYEG function in membrane protein translocation.
Andrew Hellewell Andrew is a BBSRC-funded DTG student who joined the group in 2007 having obtained a BSc at the University of York. Jointly supervised with Eric Hewitt, he is using cell biological methods to explore the origins of toxicity in amyloid assembly.
Clare Pashley Clare is also a BBSRC-funded DTG student joined the group in 2007 from the University of York. She joined the folding team and is using NMR and other methods to elucidate the structural properties of unfolded proteins.
Nathalie Valette Nathalie is in the final year of the Wellcome Trust 4-year PhD programme and is working in Chemistry with Stuart Warriner to bring the tools of chemical synthesis to the problem of amyloidosis. Using novel designs, the aim is to develop new avenues for inhibition of protein-protein interactions involved in amyloid assembly.
Aneika Leney Funded on a BBSRC CASE award (jointly with Dr Alison Ashcroft) with Waters Corporation. Aneika's project concerns pilus formation mechanisms in pathogenic E.coli. She joined the group in 2008 having graduated in Biochemistry from the University of York.
Ricardo Tome Ricardo joined the group in 2007 as a visiting PhD student from Porto, Portugal. Supervised jointly with Dr Sandra Marcedo-Ribiero he is studying nucleation mechanisms of Ataxin 3.
Dr Bethny Morrissey Bethney joined the group in 2009 on a project in collaboration with Alison Ashcroft and Gabriel Waksman (Birkbeck College, London) that focusses on the use of mass spectrometry to decipher the mechanism of pilus formation. Bethney completed her PhD in the University of Sydney, Australia and is funded by the BBSRC.
Alessandro Sicorello Alessandro came to Leeds from Florence in 2008 to join the Wellcome 4-year PhD scheme. He is using NMR and other methods to elucidate how ataxin 3 self-assembles into amyloid.
Christopher Wilson Chris joined the group in 2009 funded by BBSRC. Working in Dr David Brockwell's group (co-supervised by Prof Radford) he is investigating how force is used to unfold proteins, including those that are aggregation prone.
Lindsay McMorran Lindsay joined the group in 2009, having completed her BA in Chemistry in Cambridge, Lindsay joined the group to investigate the mechanism of membrane protein folding. She is jointly supervised with Dr David Brockwell.
Dr Morwenna Porter Morwenna joined the group in 2009. Having completed a postdoc at Yale, she is applying her expertise in Cell Biology to the problem of pathological bone destruction in dialysis amyloidosis. She is funded by the Yorkshire Kidney Research Fund on a project funded jointly with Dr Eric Hewitt.
Dr Maya Pandya Maya joined us in 2010 funded by the Wellcome Trust. She is working on a project to investigate the role of glycosamino glycans in modulating the structural mechanism of amyloid assembly of A-beta and amylin.
Dr Oliver Farrance Oliver graduated with a PhD in Physics from the University of Sheffield. Funded as part of a large BBSRC-funded LoLa award with Prof Colin Kleanthous (York), Oliver's role is to use force spectroscopy to determine how colicins intoxicate cells. He is jointly supervised with Dr David Brockwell.

Associated with the Group

Dr David Brockwell David is a lecturer in the Faculty of Biological Sciences and a member of the Astbury Centre. More information can be found at http://www.fbs.leeds.ac.uk/staff/Brockwell_DJ/

Past Group Members - where are they now?

Julia Ishola Julia was Prof. Radford's personal assistant from 2006-7.
Saleesha Mohammed Saleesha was Sheena Radford's PA from 2007-8.
Ann Holland Ann had an important role in the group. Keeping us clean and tidy until 2008.
Dr Walraj Gosal Walraj (Wooley) brought experience in Physics and Biochemistry from 2004-6. His project was to develop AFM methods for the analysis of amyloid fibrils and to study the mechanism of fibril assembly on surfaces. This project involved collaborations with Neil Thomson and Alastair Smith (Physics). On leaving the group he moved to Southwestern University, Texas.
Dr Claire Friel Claire was in the immunity protein folding team and having completed her PhD in 2003 she extended her studies into the mechanism of protein folding as a post-doctoral assistant. Having mapped the structures of intermediates and transition states in Im9 folding she used ultra-rapid methods to analyse the early events in folding and mutagenesis to investigate residual strucure in the unfolded state. She left in 2007 when she joined the Max-Planck Institute in Dresden.
Tomoko Kawakami Tomoko joined the lab from Japan to gain research experience in molecular biology and protein purification and in protein folding mechanisms. She also studied the mechanism of protein folding using single molecule FRET measurements. Since leaving in 2007 she returned to Japan to continue her work.
Dr Graham Spence Graham completed his PhD in 2004 in the group. He worked as a postdoc on the mechanism of folding of the B domain of protein A using laser temperature jump measurements and the development of diffusion collision methods for prediction of the rates of folding and unfolding. He left the group in 2007 and joined Avacta.
Dr Kirstine Anderson Kirstine joined the group in 2005 as a post-doctoral research fellow. She brings skills in NMR and molecular biology to the group. She is now working on a project with Alastair Smith and David Brockwell to elucidate the mechanism of mechanical unfolding of different proteins, specifically, the mechanism of unfolding when the protein is pulled in different directions.
Dr David Smith Having gained his PhD in the group in 2003, David carried out postdoctoral work in Australia. He then rejoined the group for one year to continue his studies of the structure of amyloid fibrils. In 2007 he started a new project working in collaboration with Dr Alison Ashcroft to use mass spectrometry to elucidate the molecular mechanisms of fibrils assembly. He left the group in 2010 to take up a lectureship at Sheffield Hallam University.
Dr Stuart Knowling Having graduated from Leeds in 2002, Stuart joined the group to study for a PhD in Immunity protein folding. His project used protein redesign and protein engineering to tailor the folding properties of Im7 using a combination of stopped flow analysis, protein engineering and studies of synthetic peptides. Having undertaken a postdoc in Prof. Peter Stockley's laboratory in Leeds, he moved to San Diego to take up a second postdoctoral position.
Dr Sara Pugh Sara was a Wellcome Trust funded 4-year PhD student. She developed novel ways of labelling proteins with fluorescent tags for measuring protein folding at the single molecule level using FRET and is now using single molecule methods to analyse different conformational states of bacterial immunity proteins. She is currently undertaking a postdoc in Leeds.
Dr Thomas Jahn Thomas finished his PhD as part of our Wellcome Trust funded 4-year PhD programme. He focussed on using NMR together with kinetic analyses to determine the structure of monomeric percursor states and the mechanism of assembly of amyloid fibrils. He was jointly supervised with Prof. Steve Homans (NMR). Having secured a prestigious Wellcome Trust Fellowship, he is now continuing his studies on amyloidosis at the University of Cambridge.
Dr Victoria Morton Victoria completed her PhD in the group as a Wellcome Trust funded 4-year PhD student. She used kinetic methods to examine the role of intermediates in tailoring the energy landscape of folding and also examined the role of topology and chemical modification in folding mechanisms. She has now switched her focus to viral assembly mechanisms with Peter Stockley and Alison Ashcroft.
Dr David Sadler David joined the group having graduated from Leeds in 2003. He worked with the mechanical unfolding team looking at the mechanism of mechanical unfolding of the small alpha/beta protein, protein L. Having successfully completed his PhD he moved into scientific editing.
Dr Isobel Morten Isobel carried out her PhD funded by Kidney Research UK. She was supervised jointly with Dr Eric Hewitt. She was our resident cell biologist and studied the role of the cell in beta-2 microglobulin amyloidosis. She is currently a postdoctoral research in Prof Nigel Hooper's group in Leeds.
Dr Jennifer Clark Jennifer joined the group in 2004 having completed her degree in Chemistry at the University of York. She has just completed her PhD on single molecule methods to study folding and binding. She is now continuing studies of single molecules with Dr Ben Schuler (Zurich)
Dr Eleanore Hann Eleanore completed her PhD in 2008 funded by the Institute of Molecular Biophysics at the University of Leeds. Her project was to analyse protein-protein interactions using single molecule mechanical experiments in collaboration with David Brockwell. She is now training to become a medical biochemist in the NHS
Dr Rebecca Rose Becky joined the group with a MChem in Chemistry from the University of Bath in 2004. She was funded on a CASE award with Dr Alison Ashcroft and Micromass UK. Becky used mass spectrometric methods to determine the mechanism of assembly of beta-sheet proteins into amyloid fibrils and bacterial pili. Having successfully completed her PhD she moved to Albert Heck's laboratory in Utrecht to continue her research into biological mass spectrometry.
Dr Katy Routledge Katy was funded on our Wellcome Trust 4 year PhD programme. In her project she determined the role of specific residues in aggregation of beta-2 microglobulin in the early stages of assembly as well as in the final fibrillar form. Having undertaken a short postdoc project with Dr Eric Hewitt to investigate the biological response of cells to amyloid funded by the Yorkshire Kidney Research fund, she moved to the Scripps Research Institute USA to a second postdoc in Bill Balch's laboratory.
Dr Johnny Hodkinson Johnny joined the group in 2005 to study for a PhD in the use of mass spectrometry to analyse protein assembly. Supervised jointly with Alison Ashcroft, his project was to identify and characterise rare species and early oligomeric states in amyloid assembly using hydrogen exchange and real-time measurements of assembly using mass spectrometry. He graduated having successfully completed his PhD in 2009.
Barbara Tynan-Connolly Barbara visited the group for 8 weeks as part of her PhD studies at University College Dublin. She worked in the amyloid team and investigated the role of proline residues in fibril formation.
Dr Gerard Husymans Gerard completed his PhD in 2008 funded by the Wellcome Trust. He worked on a project in collaboration with David Brockwell and Steve Baldwin to measure the mechanism of folding of the beta-barrel bacterial outer membrane protein, pagP. He is now working as a postdoc with Prof Steve Baldwin in Leeds.
Dr John Reader John finished his PhD in 1998. He looked at the mechanism of folding of a blue cupredoxin protein, pseudoazurin. He used protein engineering, structural methods and kinetics to determine how this Greek-key protein folds. After postdoctoral research at The Scripps Institute, he became an assistant professor at University of North Carolina, USA.
Dr Sunita Kulkarni Sunita was a BBSRC funded post-doc working on the mechanism of protein folding using stopped-flow methods, NMR, mass spectrometry, CD and fluorescence.
Dr Gary Thompson Gary was funded by The Wellcome Trust to determine the solution structure of the proteins we are studying using multi-dimensional NMR methods. He left in 1999 and joined Prof Homan's group here in Leeds.
Dr Joe Coyle Joe worked on chaperone assisted protein folding. He used a range of methods to delineate the relationship between folding in vivo and in vitro. In addition, he used substrate analogues to map the binding sites on GroEL for substrate. Having worked as a postdoc in the USA, he now works in the Biotech industry in Cambridge.
Dr Neil Ferguson Neil finished his PhD in the group in 2000. The aim of his work was to clone and overexpress a small protein domain, to elucidate its solution and crystal structure and to look at its folding properties. He also worked on the bacterial immunity protein project. Having worked in Cambridge with Prof. Alan Fersht he is now a lecturer at University College Dublin.
Dr Richard Argent Rich was funded by the Wellcome Trust to investigate the role of protein unfolding in retrograde transport of the toxin ricin. This project was a collaboration with Prof Mike Lord and Dr Lynne Roberts (University of Warwick)
Dr Neil Kad Neil was funded by industry and the BBSRC to use his expertise to try to understand the mechanism of fibrillogenesis of beta-2 microglobulin. He has now moved to the Department of Molecular Physiology and Biophysics, at the University of Vermont. He came back to the UK in 2008 where he took up a lectureship at the University of Essex.
Dr Andrew Capaldi Andrew gained his PhD in the group in 1999 and continued as a postdoc. His major interest was the fundamental biophysics of protein folding. Using a number of methods he defined the mechanism of folding of the Greek key protein, pseudoazurin. In addition, he looked at the folding of the all helical bacterial immunity proteins. This combined folding studies with functional studies that are being worked on by our collaborators (Dr Colin Kleanthous) at the University of York. Since leaving Leeds, he returned to the USA where he moved into systems biology at UCSF and Harvard. He is now an Assistant Professor at the University of Arizona, USA.
Dr Stan Gorski Stan completed his PhD in the group investigating the folding of pseudoazurin and the immunity proteins. His studies focussed on using hydrogen-exchange and NMR to delineate the structure and cooperativity of partially folded intermediates. After working as a postdoc for several years at NIH, Bethesda Maryland, he became an editor of EMBO J in Heidelberg.
Luc Bousset Luc was a visitor from Gif-sur-Yvette, Paris where he worked in the group of Ron Melke. He was funded by the EU Marie-Curie Training scheme and came to Leeds to use AFM and FTIR along with other methods to analyse the structural conversion in the prion protein, Ure2p. We carried out this work in collaboration with Dr Neil Thomson in Physics and Astronomy (Leeds).
Dr Victoria McParland Victoria completed her PhD in the group in 2001. She continued as a post-doc in the laboratory investigating the mechanism of protein misfolding and aggregation of beta-2 microglobulin in fibrillogenesis and disease. After two postdoctoral positions in the USA, Victoria moved to EMBL Heidelberg, where she is continuing her research.
Dr Geoff Howlett Geoff is an Associate Professor who visited the lab from the Department of Biochemistry at the University of Melbourne for a short sabbatical from May 2003.
Dr Tali Gidalowitz Tali visited the lab from Yair Argon's lab in Chicago and analysed the role of Grp94 in folding and assembly in the cell. She is now a postdoc working with Rick Morimoto, Chicago, USA.
Dr Tony Blake Tony was jointly supervised by Prof Radford and Dr Alastair Smith in Physics. Tony studied mechanical unfolding of proteins and the role of the sequence and solution conditions in determining the mechanism and unfolding properties of different folds.
Dr Susanne Cranz Susanne was a Marie Curie funded student on a 12 month visit from the University of Zurich. She looked at the role of helical propensities in the folding of Im9 studied by a combination of protein engineering and equilibrium and kinetic methods
Doreen Berger Doreen was Prof. Radford's personal assistant until she retired in 2005.
Dr Sue Jones Sue was a long time member of the group. She has now taken up a post at the University of Bradford.
Dr Rebecca Zinober Rebecca was a Wellcome Trust 4 year PhD student who was a physicist by training. She was jointly supervised with Dr Peter Olmsted (IRC in Polymer Sciences, Leeds) and Dr Alastair Smith (Physics & Astronomy) and developed computational methods to analyse the mechanism of mechanical unfolding of proteins.
Dr Eva Sanchez-Cobos Eva was a member of the group from 2003 to 2005 having won her own Fellowship from FEBS. She used temperature jump and stopped flow methods to analyse the early stages in immunity protein folding. She has since taken up a position at the University of Granada, Spain.
Dr Clemens Stilling Clemens has completed his PhD studying the mechanism of amyloidosis of beta-2 microglobulin at the molecular level. He also attempted to design RNA aptamers as inhibitors of amyloidosis. He is now working in research in industry.
Dr Sarah Myers Sarah completed her PhD studies in 2005, studying protein assembly using AFM and its combination with proteolysis and mass spectrometric analyses to assess the structure of amyloid precursors and fully assembled amyloid fibrils. The project involved collaborations with Neil Thomson (Physics) and Alison Ashcroft (Mass Spec). She is now working in research support at the School of Dentistry, University of Leeds.
Dr Andrew Smith Andrew used mass spectrometry to determine the mechanism of assembly of proteins into amyloid fibrils and, in collaboration with Prof. Peter Stockley, the assembly of virus capsids.
Dr Toni Borysik Toni completed his PhD in the group in 2005 developing mass spectrometric methods for the analysis of conformational ensembles of partially folded states and non-covalent assemblies. He then continued as a postdoctoral researcher working on a joint project with Eric Hewitt to determine the identity of biological factors that play a key role in initiating fibril formation of beta-2 microglobulin. He is now a postdoc at the University of Nottingham.
Yee-Foong Mok Mok visited the group for 3 months from Geoff Howlett's group at the University of Melbourne, Australia. He studied the effect of the binding of apolipoprotein E to fibrils of apolipoprotein CII and beta-2 microglobulin using hydrogen exchange and NMR.
Dr Colin Grant Colin joined the group in October 2006 and brings expertise in mechanical engineering to the group. His project, in collaboration with David Brockwell, and Neil Thomson aims to use the AFM to elucidate the mechanical properties of amyloid fibrils. He is now undertaking a second postdoc in the School of Physics and Astronomy at the University of Leeds.
Ancilla Neu Ancilla joined the lab for a year as an ERASMUS student from Regensberg, Germany. She worked on the mechanism of pilus assembly using NMR and other biophysical approaches.
Dr John White John is a synthetic organic chemist who worked with Dr Stuart Warriner (School of Chemistry) on an exciting project which used native chemical ligation for the chemical synthesis of beta-2 microglobulin. This synthetic route allows the incorporation of novel amino acids and the analysis of their effect in structure, folding and aggregation. He left the group in 2009 to work in idustry before taking up a position in education.
Helen Saunders Coming from Melbourne, Helen joined the lab for a summer project in 2008 to investigate Ataxin 3 aggregation as part of her PhD studies with Prof Steve Bottomley.
Jenny Smit Jenny was a summer visitor in 2008 and comes from Utrecht University. She investigated the folding mechanism of protein domains from the LDL receptor.
Mark Chen Mark visited the group from MIT in 2009 on a collaborative project with Barbara Imperiali. His project focussed on using chemical and semisythetic routes to create novel glycoproteins for protein folding studies.

The group - Summer 2007	The group - May 2008

We would like to thank the following organisations for the funds to support our research:
BBSRC, MRC, EPSRC, The Royal Society, The Wellcome Trust, and The University of Leeds.