Structure and dynamics of prions and their ligand interactions
Tel: 020 7679 5128
Courtauld Building, Room 101B
List of Funders
Medical Research Council
National Institute for Neurological Disorders and Strokes (NINDS)
Hope Center for Neurodegenerative Diseases
Protein structure and folding
Super-resolution fluorescence microscopy
Atomic force microscopy
Mark Batchelor (Researcher)
Laszlo Hosszu (Senior Researcher)
Daljit Sangar (Researcher)
Yuanzi Sun (PhD Graduate Student, UCL)
List of collaborators
Matthew D Lew (Department of Electrical & Systems Enginnering, Washington University in St Louis)
Conrad C Weihl (Department of Neurology Washington University in St Louis)
Steven Lee (Department of Chemistry, University of Cambridge)
Sheena Radford (Astbury Centre for Structural Molecular Biology, University of of Leeds)
Richard Session (Department of Biochemistry, University of Bristol)
Mervyn Miles (Centre for Nanoscience and Quantum Information, University of Bristol)
Jonathon P Waltho (Biomolecular NMR, University of Sheffield)
Helen Saibil (Department of Crystallography,
Birkbeck College and Institute of Structural Molecular Biology, University of London)
Chiu C Tang (Diamond Light Source, Harwell Campus, Oxfordshire)
Katherine McAuley (Diamond Light Source, Harwell Campus, Oxfordshire)
Ian Collinson (Department of Biochemistry, University of Bristol)
Leo Brady (Department of Biochemistry, University of Bristol)
David Scott (National Centre for Macromolecular Hydrodynamics, University of Nottingham)
We aim to understand the central problem in the prion mechanism; what is the change in shape that distinguishes normal prion protein, PrP C , from its rogue form, PrP Sc , and how does it come about? Specifically, we are asking what the structural causes are for becoming a prion, what the common drivers are for their replication, and whether the same principles underlie other diseases, both inside the central nervous system and in the rest of the body.
We combine biophysical techniques with nanoscopic imaging to study the structure, folding and dynamics of prions, both in isolation and with likely binding partners, in order to develop new strategies against prion diseases. We have developed nanoscopic imaging to observe amyloid structures over extended times through transient amyloid binding (TAB) of dye molecules. The movie shows real time TAB imaging of Aβ42 fibril remodelling over 48 h by the anti-amyloid compound epi-gallocatechin gallate (from: Spehar et al. 2018)
Super-Resolution Imaging of Amyloid Structures over Extended Times Using Transient Binding of Single Thioflavin T Molecules.
Spehar K, Ding T, Sun Y, Kedia N, Lu J, Nahass GR, Lew MD, Bieschke J. Chembiochem. 2018
Glucose directs amyloid-beta into membrane-active oligomers.
Kedia N, Almisry M, Bieschke J. Phys Chem Chem Phys. 2017
Amyloid-β(1-42) Aggregation Initiates Its Cellular Uptake and Cytotoxicity.
Jin S, Kedia N, Illes-Toth E, Haralampiev I, Prisner S, Herrmann A, Wanker EE, Bieschke J. J Biol Chem. 2016
Small-molecule conversion of toxic oligomers to nontoxic β-sheet-rich amyloid fibrils.
Bieschke J, Herbst M, et al. Nature Chem Biol. 2011
EGCG remodels mature alpha-synuclein and amyloid-beta fibrils and reduces cellular toxicity.
Bieschke J, Russ J, Friedrich RP, Ehrnhoefer DE, Wobst H, Neugebauer K, Wanker EE. Proc Natl Acad Sci U S A. 2010
Opposing activities protect against age-onset proteotoxicity.
Cohen E, Bieschke J, Perciavalle RM, Kelly JW, Dillin A. Science. 2006
Autocatalytic self-propagation of misfolded prion protein.
Bieschke J, Weber P, Sarafoff N, Beekes M, Giese A, Kretzschmar H. Proc Natl Acad Sci U S A. 2004