CRM: Centro De Giorgi
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Reverse mathematical methods for reconstructing molecular dynamics in single cell

Direct in-cell observation of structural progression of amyloid-β Arctic mutant aggregation

speaker: Meng Lu (University of Cambridge)

abstract: Hereditary Aβ mutations, such as the Arctic Glu22-to-Gly (E22G) mutation, lead to increased intracellular accumulation of β-amyloid and disease onset at a young age (1, 2). It remains largely unknown, how the Arctic mutation leads to aggressive protein aggregation and increased toxicity. Here, we constructed stable cell models expressing wild-type (WT) and E22G Aβ42 fused to mCherry to study the aggregation kinetics of the Arctic Aβ mutant and its heterogeneous structural forms. Arctic mutant peptides assemble to form fibrils at a much faster rate than WT peptides and rapidly accumulate to form fibril bundles or clusters and later aggresomes. All aggregate species, as revealed by fluorescence-lifetime imaging (FLIM) (3) and 3D Structural Illumination Microscopy (SIM), display a lowered fluorescence lifetime and highly compact structures with a strong affinity among individual fibrils. The aggregates formed by Arctic mutant Aβ are also more resistant to intracellular degradation than their wild-type counterparts.

Tue 16 Oct, 16:00 - 16:30, Aula Dini
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