Sathyamoorthi Pilot Project Summary

The fluorescence of organic molecules can be exploited to create powerful tools for the unravelling of complex biological phenomena. The combination of sensitive and specific small-molecule fluorescent sensors with revolutionary advances in optical imaging has greatly clarified the role of cations in biological systems. Few small molecule tools exist for the study of Li⁺ in physiological contexts. While naturally found in the body only in trace amounts, when given exogenously, Li⁺ has a profound impact on neurochemical signaling and neurobiological homeostasis. Indeed, Li₂CO₃ is a first line treatment for Type 1 Bipolar Disorder (BD-1) because it is surprisingly effective in mood stabilization. Despite extensive research, a comprehensive picture of lithium’s mechanism of action and its distribution in the brain post-treatment remain elusive. The rationale for this research is that the development of highly sensitive and specific Li⁺ probes will pave the way for experiments illuminating its effect on neuronal populations. The expected outcome of this research is the completion of several steps towards a better understanding of the pathology of BD-1 and the role of Li⁺ in ameliorating the symptoms of this disorder. This will positively impact the development of next-generation safe and effective BD-1 therapeutics.

The Specific Aims of this Pilot Project are:

1. To Develop New Classes of Ratiometric and Intensity-Based Fluorescent Lithium Sensors. These will be designed to be cell permeable and to detect Li⁺ selectively and at therapeutically relevant concentrations.
2. To Develop New Photocaged Lithium Complexes. These will be designed to decompose upon irradiation with Near-IR light. Such tools will provide investigators with the ability to deliver a controlled bolus of Li⁺ to target cell populations for the analysis of downstream effects.