Nanoparticle-Based Axonal Transport Probe for Screening Neurodegenerative Diseases
The dynein-driven retrograde axonal transport delivers intracellular cargoes from the axonal terminal towards the soma, which regulates various physiological functions of neurons. The ability to visualize any deficit in intra-axonal transport in real-time will enable us to detect transport related impairment in neurons. Conventionally, fluorophores like organic dyes, fluorescent proteins and quantum dots were used for tracking dynein movement. However, technical limitations such as poor photo-stability (photo-blinking and photo-bleaching), high auto-fluorescence, restricted imaging depth and the need for sophisticated microscopy prevent their wide scale applications. Here, we introduce a novel nanotechnology-based tool for imaging intra-axonal transport of neurons. The different patterns of anterograde and retrograde axonal transport disruption can be used to screen and separate primary axonal disorders, such as pantothenate kinase-associated neurodegeneration (PKAN) from primary somatic degenerations, in Huntington’s disease. We propose to image and measure axonal transport with upconversion nanoparticles in neurons derived from fibroblasts of diagnosed subjects, which retain their disease characteristics. Although this nanotechnology will be translatable to many other neurological diseases, as a proof of concept and feasibility, we will be focusing on the most common neurodegenerative diseases, Alzheimer’s Disease (AD) and Parkinson’s Disease (PD). Axonal transport impairment has been associated with AD and PD due to accumulation of dysfunctional proteins. By utilizing this pathogenesis at a cellular or molecular level, we aim to introduce an upconversion-based nanotechnology as a convenient tool to enable systematic characterization of the impairment of axonal transport process. Our goal is to maximize the potential of nanotechnology for improved understanding of key pathological and early signs of neurodegeneration. We will be a unique multidisciplinary team of expert scientists with extensive experience and knowledge with regard to the proposed research project. This has enabled us to be amongst the front runners to advance this highly specialized research field of neuroscience.
Some knowledge of the following disciplines would be desired: Upconversion Nanoparticles, Human Stem Cells Differentiation and Cell Culturing, Bioimaging, Molecular Biology.