MRC Prion Unit and Institute of Prion diseases


Jan Bieschke

Structure and dynamics of prions and their ligand interactions

Jan Bieschke


Tel: 020 7679 5128
Courtauld Building, Room 101B


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Research Synopsis

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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)

Selected Publications

Desmin forms toxic, seeding-competent amyloid aggregates that persist in muscle fibers
Kedia N, Arhzaouy K, Pittman SK, Sun Y, Batchelor M, Weihl CC, Bieschke J; PNAS 2019

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