Datta Group

Chemical Biology & Molecular Imaging

Sensors for Signal-Mediating Phospholipids

Phospholipids are essential structural constituents of the cell membrane. These molecules mediate almost all cell-signaling events and regulate essential cell processes like membrane fusion in synapses, cytoskeletal rearrangements in cell movement, and phagocytosis in cell death. Further, defects in phospholipid metabolism are linked to multiple diseases including cancer, bipolar disorder, and type-2-diabetes. Dynamic changes in phospholipid concentrations, locations, and distributions on membranes are proposed to act as initiating flags for signaling events. When the phospholipid distribution changes, so does the signal. Hence, visualizing phospholipid dynamics on the cell membrane will provide ultimate access to understanding the basis of cell signaling and afford pathways for therapeutic intervention. In this emerging context, optical probes for visualizing phospholipids in living cells and organisms are vital tools for monitoring phospholipid dynamics. The major challenge is: to selectively light up one type of phospholipid amongst the numerous structurally similar variants in the entire cellular background. Importantly, the detection strategy has to be reversible in order to be able to track dynamic spatiotemporal changes. We engineer protein and peptide-based scaffolds to develop ratiometric and ‘turn-on’ fluorescent sensors with reversible optical response that enable live imaging of signaling phospholipids like phosphatidylserine and phosphoinositides.