Investigating and Manipulating Neurodegeneration-Related Protein Oligomers Using Nanopore and X-ray Techniques

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Date 08.02.2024
Hour 14:0015:00
Speaker Jinghui Luo received his Ph.D. degree in 2014 from Leiden University under the supervision of Prof. Jan Pieter Abrahams. After postdoctoral research with Prof. Hagan Bayley at Oxford University, he started his independent career at the Paul Scherrer Institute and then obtained his tenure in 2022.
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Category Conferences - Seminars
Event Language English

Protein oligomers, pivotal in both physiological and pathological processes such as Alzheimer’s disease, present challenges in comprehending their intricate intermediate and diverse structures. Our research leverages specialized biological nanopore approaches and X-ray techniques to explore and manipulate protein oligomers in diverse settings, ranging from in vitro to in vivo. We have engineered a stable Alzheimer’s Aβ42-oligomer mimic on the α-hemolysin (αHL) nanopore for drug development and investigated the conformational kinetics and trapping of Parkinson’s α-Syn in an αHL nanopore for small compound screening. Additionally, our nanopore sensing probes reveal LL-37 fragments' oligomeric equilibrium correlated with antimicrobial effects.

To impede toxic oligomer formation, we employed molecular glues to evaluate the trapping and degradation potential of amyloid clusters in C.elegans. Our time-resolved small angle X-ray scattering and C.elegans experiments provide insights into the in vivo and in vitro condensation of tau and α-synuclein in the presence of molecular glues. Furthermore, we observed the conversion of metal ions into metallic nanoparticles induced by amyloid clusters by using scanning transmission X-ray microspectroscopy. Looking ahead, the integration of nanopore and X-ray techniques holds great promise for advancing our understanding of neurodegeneration-related oligomers, offering valuable insights for therapeutic development.
 

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