This proposal describes a multi-disciplinary research program that aims to? develop, validate, and disseminate microfluidic technologies for quantitative? studies of protein aggregation and aging. Protein aggregation is associated with? aging and with a number of human diseases that affect both quality and duration? of life. Many fundamental aspects of protein aggregation remain elusive,? including connections between protein aggregation and toxicity, and the? connection between protein aggregation and initiation and progression of? diseases. Microfluidic platforms will be developed to understand these complex? processes from both bottom-up and top-down perspectives. Bottom-up, new? droplet-based microfluidic systems will be developed to characterize? quantitatively the connection between protein aggregation and toxicity in vitro.? This system will allow the reproducible real-time generation, manipulation, and? characterization of aggregates for in vitro and in vivo toxicity screens.? Multidimensional statistical analysis of toxicity patterns obtained in these devices? may elucidate the connection between protein aggregation and toxicity, clarify? the mechanism of action of existing drug candidates that target aggregation, and? accelerate development of new drugs and drug cocktails. Top-down, microfluidic? technologies will be developed to induce and monitor aggregation in vivo with? high spatiotemporal resolution, and to observe the effects of aging, physiological? state, neuronal activity, and presence of drug candidates on the initiation and? progression of protein aggregation diseases. These two technologies will be? used together to understand protein aggregation and aging, and may lead to new? hypothesis and molecules for controlling these processes.?
Showing the most recent 10 out of 24 publications
