Title:

Activity-Based Sensor Development for Imaging Iron(II)

An activity-based sensor is a single molecule that selectively reacts with a target analyte, undergoing a chemical change resulting in fluorescent properties. Analytes of interest include peroxides which produce reactive oxygen species (ROS), or ‘free radicals’, which can cause substantial damage to the cells that make up an organism. Peroxides are capable of degrading cellular membrane function by attacking individual phospholipids within the bilayer, a process implicated in varying forms of cancer and neurodegenerative disease. This project aims to evaluate the attachment of an activity-based sensor that is sensitive to the presence of ferrous cations, to a phospholipid using synthetic and metabolic label strategies that will enable incorporation of the sensor into a cell or organelle membrane. The selective, fluorescent readout of activity-based sensors enable detection of analytes including reactive species within the cellular environment. Advances in biorthogonal chemistry that have enabled functionalization of biomolecules, including lipids will be leveraged to anchor activity-based sensors at membranes in distinct cellular environments. Analyte production will be observed using fluorescence microscopy and will report on changes in membrane structure and function. Setting this fundamental precedent will determine future directions for activity-based sensor integration into cellular environments, for the detailed analysis of disease pathways related to the production of ferrous cations.

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