Specific tests for Alzheimer’s disease (AD) diagnosis are currently unavailable, despite AD being the leading cause of dementia. One hallmark of AD progression is the aggregation of tau proteins into paired helical filaments and neurofibrillary tangles, which is accelerated by the hyperphosphorylation of Tau proteins. However, the mechanism by which the hyperphosphorylated tau accelerates protein aggregation is not completely understood. Furthermore, detecting and disrupting such aggregated forms through the blood-brain barrier (BBB) remains a significant bottleneck in developing AD diagnostics and therapeutics. At the same time, quantum dots (QDs) have shown tremendous potential in penetrating the BBB to diagnose brain cancer, as well as detecting and disrupting protein aggregates in other neurodegenerative diseases such as Parkinson’s disease. QDs are an attractive diagnostic material due to their fluorescence-emitting capabilities, nanoscale size that allows penetration of the BBB, chemical stability, solubility, and facile synthesis. However, QDs have not yet been assessed for their ability to detect and disrupt hyperphosphorylated tau tangles. Hence, the aims of this project are two-fold: 1) to unravel the mechanisms and energetic barriers of normal and hyperphosphorylated tau protein aggregation by building three-dimensional atomistic models of aggregated structures and performing classical and enhanced sampling molecular dynamics simulations on these models; 2) to predict the potential of QDs in binding to and disrupting hyperphosphorylated tau tangles though polarized ligand docking and free-energy calculations. Upon identification of potential QD-binding signatures, these QDs will be synthesized and tested in vitro and in vivo through collaborative efforts with the goal of translating this work into clinical diagnostic applications for AD in the future.
Figure 1. Microtubule-associated protein tau (MAPT) functions in the healthy brain (left) and a brain with Alzheimer’s disease (AD) (right). Self-association and excessive post-translational modifications of Tau proteins result in the formation of neurofibrillary tangles and cause neurodegeneration in AD patients. Targeting the tau aggregates using Quantum Dots could help develop potential diagnostics and/or therapeutics for AD.
Engineering and Characterizing Programmable Interaction Graphs in a Trapped Ion Quantum Simulator
Summary Quantum simulators have the potential to bring unprecedented capabilities in areas such as the discovery of new materials and drugs. Engineering precise and programmable interaction graphs between qubits or spins forms the backbone of simulator applications. The trapped ion system is unique in that the interaction graph between qubits can be programmed, in […]
July 24, 2018
Scanning Tunneling Microscopy of Quantum Materials, Devices and Molecules
Summary This project advances our ability to characterize and study novel quantum materials, quantum devices, and even individual molecules at the atomic level. By combining Non-Contact Atomic Force Microscopy (NC-AFM), Scanning Tunneling Microscopy (STM) and scanning gate methods, we correlate spatial information with transport properties and can locally manipulate charge, spin and structural states. […]
January 28, 2019
Reliably operating noisy quantum computers
Summary The overall goal of the project is to develop practical methods to be able to reliably run useful applications on near-term quantum computers. This requires identifying and overcoming the ubiquitous errors that currently limit quantum computing capabilities. Traditional methods of quantifying errors in quantum computers fail to predict how errors affect the output of […]
January 22, 2020
Line-Scanning optical coherence tomography system for in-vivo, non-invasive imaging of the cellular structure and blood perfusion of biological tissue
Summary Optical coherence tomography (OCT) is an optical imaging method that allows for in-vivo, non-invasive imaging of the structure and vasculature of biological tissue. Commercially available, clinical OCT systems utilize point-scanning method to acquire volumetric images over a large surface with typical frame rates of ~ 30 frames/ second. Since living biological tissue is constantly […]
August 27, 2019