Quantitative spatio-temporally resolved fluorescence microscopy imaging of fast dynamic processes via massively parallel Fluorescence Correlation Spectroscopy (mpFCS)

This interdisciplinary research proposal at the interface between biophysical chemistry, optics/photonics, cell biology and molecular medicine, aims to solidify instrumentation and further advance a new methodology for quantitative spatio-temporally resolved fluorescence microscopy imaging via massively parallel Fluorescence Correlation Spectroscopy (mpFCS) that we have recently developed.

The methodology, which has the ultimate, single-molecule sensitivity, will be used in basic and translational studies to:Aim 1a.

Dissect in live cells kinetic mechanisms through which gene transcription networks self-adjust their essential variables and control their own biological function.Aim 1b.

Provide in live cells quantitative biophysical data and mechanistic insights on how the functional dynamics of oligodendrocyte transcription factor (OLIG2) can be rescued by treatment with novel prospective drug candidates. Aim 2.

Implement this new technology in a translational research study aiming to develop a reliable and affordable non-immune, blood-based assay for early diagnosis of amyloid diseases, such as Alzheimer’s disease (AD).Aim 3a. Development of a system for massively parallel dual-color Fluorescence Cross-Correlation Spectroscopy (mpFCCS).Aim 3b.

Develop a fiber optic probe to allow parallelized FCS recordings in behaving animals.