BEGIN:VCALENDAR
VERSION:2.0
PRODID:icalendar-ruby
CALSCALE:GREGORIAN
METHOD:PUBLISH
BEGIN:VEVENT
DTSTAMP:20261016T022328Z
UID:https://www.mpip-mainz.mpg.de/events/26670/536464
DTSTART:20201027T130000Z
DTEND:20201027T140000Z
CLASS:PUBLIC
CREATED:20201129T151418Z
DESCRIPTION:Amyloid fibrils are well-ordered supramolecular polymers consis
 ting of thousands of protein molecules connected via intermolecular hydrog
 en bonds. For intrinsically disordered proteins (IDP)\, amyloid form is th
 ermodynamically more stable than the native form\, and its formation in hu
 man body can lead to pathology. Namely\, misfolding of small intrinsically
  disordered neuronal protein α-synuiclein is a hallmark of Parkinson's di
 sease. The fibrillization is an autocatalytic process that can be induced 
 by small amounts of pathological fibrils in a prion-like manner. We studie
 d detailed kinetic mechanism of the α-synuiclein fibrillization and have 
 shown that atypical sigmoidal reaction kinetics and exponential distributi
 on of the length of formed fibrils are the results of a two-step autocatal
 ytic cycle that includes fibril elongation via binding monomers to the end
 s and formation of new fibril ends due to fibril breaking [1]. This allowe
 d us to identify the fibril ends as the bottleneck of the process and thus
  the most prospective target for fibrillization inhibitors. We designed se
 veral proteins and peptides that selectively bind to the fibril ends and b
 lock their growth by creating a steric hindrance [2\,3]. This approach per
 mits inhibition of fibril formation at inhibitor concentrations orders of 
 magnitude lower than the concentration of monomeric α-synuclein. In my ta
 lk\, I will focus mostly on the application of mathematical models for det
 ermination of the reaction mechanism based on kinetic data and on design o
 f experiments for refining the models and proving the mechanism.\nVortrage
 nde(r): Dr. Volodymyr Shvadchak
LAST-MODIFIED:20201201T130401Z
LOCATION:Digital see link
ORGANIZER;CN=Oleksandra Kukharenko:mailto:kukharenko@mpip-mainz.mpg.de
SUMMARY:Misfolding of IDPs into amyloid fibrils: From mechanism studies to 
 inhibitor development
URL;VALUE=URI:https://www.mpip-mainz.mpg.de/events/26670/536464
END:VEVENT
END:VCALENDAR