Jan Bieschke
Research Synopsis
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)
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