2007 NIH Director's Pioneer Award Program (DP1)

University Of Chicago, Chicago IL

Investigators

Linked publications & trials

Abstract

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