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SUMMARY:Heterotypic Amyloid Interactions and their Impact on Amyloid Assem
 bly - Prof Frederic Rousseau\; VIB SWITCH Laboratory\, KU Leuven
DTSTART:20230210T130000Z
DTEND:20230210T140000Z
UID:TALK193711@talks.cam.ac.uk
CONTACT:Bobbie Claxton
DESCRIPTION:Abstract: Heterotypic amyloid interactions between related pro
 tein sequences have been observed in functional and disease amyloids. Whil
 e sequence homology seems to favour heterotypic amyloid interactions\, we 
 have no systematic understanding of the structural rules determining such 
 interactions nor whether they inhibit or facilitate amyloid assembly. \n\n
 Using both Ab and tau as a model system we demonstrate that proteins with 
 local sequence homology can modify fibril nucleation\, morphology and spre
 ading of aggregates in cultured cells2\,3. Depending on the type of mutati
 on such interactions inhibit or promote aggregation in a manner that can b
 e predicted from structure. We find that these heterotypic amyloid interac
 tions can result in the subcellular mislocalisation of these proteins. Mor
 eover\, equilibrium studies indicate that the critical concentration of ag
 gregation is altered by heterotypic interactions. \n\nOur findings suggest
  a structural mechanism by which the proteomic background can modulate the
  aggregation propensity of amyloidogenic proteins and we discuss how such 
 sequence specific proteostatic perturbations could contribute to the selec
 tive cellular susceptibility of amyloid disease progression.\n\nBio:Freder
 ic Rousseau is a Belgian structural biologist and biophysicist affiliated 
 with the Flanders Institute for Biotechnology (VIB) and the University of 
 Leuven (KUL). His scientific research is performed in close collaboration 
 with Joost Schymkowitz\, with whom he directs the VIB Switch laboratory si
 nce 2003. Frederic and Joost have been a scientific duo since 1998\; they 
 obtained their PhDs from the University of Cambridge\, UK and completed po
 st-doctoral research at EMBL\, Heidelberg. The research of the Switch Lab 
 integrates computational modeling\, biophysics\, cell biology\, chemical b
 iology with in vivo experiments and analysis of patient tissues to investi
 gate the mechanisms of protein misfolding and aggregation. Frederic and Jo
 ost are also scientific founders of-\, and scientific advisors to Aelin Th
 erapuetics\, fa privately held Belgian biotherapeutics company that develo
 ps the therapeutic applications of the Pept-inTM technology\, invented in 
 the Switch Lab. Frederic and Joost have authored more than 170 peer-review
 ed publication in high impact journals\, including Nature\, Cell and Scien
 ce\, and are inventors on more than 15 patents.\n
LOCATION:Kings Hedges Room 
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