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SUMMARY:Special LMNN Seminar - An all optical approach to study amyloid ag
 gregation
DTSTART:20170707T153000
DTEND:20170707T163000
DTSTAMP:20260503T100546Z
UID:82e90faf583e383981ac9d453d2d7866f99e1615eb068c6603c911ab
CATEGORIES:Conferences - Seminars
DESCRIPTION:Gabriele S. Kaminski Schierle\, Department of Chemical Enginee
 ring and Biotechnology\, University of Cambridge\, Cambridge\nUnderstandi
 ng the formation and structural characteristics of amyloid fibrils is vita
 l for the development of therapeutics for many neurodegenerative disorders
 . We have developed a fluorescence-lifetime based aggregation sensor which
  can readily be applied in vitro and in vivo\, permitting the screening of
  small molecule drugs against protein aggregation. In order to characteris
 e amyloid fibril growth\, we apply two colour total internal reflection mi
 croscopy and super-resolution imaging and demonstrate that there is hetero
 geneity in the growth rates of individual amyloid fibrils which can be att
 ributed to structural polymorphism. We also show that Tau and heparin form
  composite fibrils and thus structurally prevent seeding.\nIn order to und
 erstand the normal physiological and pathological function of alpha-synucl
 ein\, a protein linked to Parkinson’s disease\, we have applied a combin
 ation of optical and NMR spectroscopy techniques. We have discovered that 
 alpha-synuclein acts as a calcium sensor at the pre-synapse. In particular
 \, we show that a sub-group of alpha-synuclein-positive vesicles at the pr
 e-synapse is specifically responsive to changes in calcium concentrations.
  This is in contrast to VAMP-2 positive vesicles which do not form localis
 ed clusters at the pre-synapse upon calcium exposure. NMR data indicate th
 at this calcium sensing capacity of alpha-synuclein is mediated via the ne
 gatively charged C-terminus\, which\, upon calcium binding\, directly inte
 racts with synaptic vesicles. We further demonstrate that the alpha-synucl
 ein calcium sensor needs to be finely tuned as increased levels of calcium
  over a prolonged time in the presence of alpha-synuclein can directly res
 ult in pathology. Similarly\, using a cell model of Parkinson’s disease\
 , toxicity can either be prevented by a decrease in the level of alpha-syn
 uclein or by isradipine\, a voltage-gated calcium channel inhibitor.\nIn s
 ummary\, by applying primarily optical techniques we have shed light on am
 yloid protein function\, aggregation kinetics and structural characteristi
 cs which together may help to develop therapeutic strategies against vario
 us forms of neurodegenerative diseases.
LOCATION:SV 1717 https://plan.epfl.ch/?room==SV%201717
STATUS:CONFIRMED
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