HYBRID EVENT: You can participate in person at Baltimore, Maryland, USA or Virtually from your home or work.
Saurabh Awasthi, Speaker at Nanotechnology Conferences
Adolphe Merkle Institute, University of Fribourg, Switzerland
Title : Single-particle level characterization of protein aggregation

Abstract:

Protein aggregation is the hallmark of neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), etc. Early-stage aggregates, i.e., oligomers, are the key toxic species implicated in neurodegeneration, and these early aggregation species are challenging to characterize using conventional methods based on ensemble analysis. The critical challenges in using the conventional approaches such as X-ray crystallography, Nuclear magnetic resonance, and Small-angle x-ray scattering to characterize oligomers are their metastable nature and high heterogeneity with regard to both the size and shape in solution. More importantly, since only certain sized and shaped oligomeric species are toxic, the biophysical characterization of oligomers is of great interest in the quest to better understand the structure-toxicity relationship. We demonstrate that resistive pulse sensing using solid-state nanopores (a small, nanometer size hole) enables single-particle characterization of amyloid oligomers in solution in a label-free manner. Moreover, this approach can resolve the complete aggregation pathway, starting from early-stage low-n oligomers to intermediate-size aggregates and late-stage protofibrils/fibrils. Resistive-pulse sensing allows the determination of the aggregation kinetics of different protein variants. Single-particle characterization of individual oligomeric species will improve the general understanding of the structure-toxicity relationship of such aggregates and facilitate the drug development to target them.

Biography:

Saurabh Awasthi is a Group Leader at the Adolphe Merkle Institute, University of Fribourg, Switzerland. He received his PhD from the SASTRA University in 2016 for his work on advanced glycation end products induced structure- function changes in proteins. His current research involves the use of biophysical methods to determine the molecular understanding of the disease by characterizing individual protein molecules and amyloid aggregates. One focus area is the single-particle analysis of protein aggregation associated with Parkinson’s and Alzheimer’s disease.

Watsapp