With support from the Chemical Measurement and Imaging Program and co-funding from the Chemical Structure, Dynamics and Mechanisms Program in the Division of Chemistry, Professor Maolin Guo and his group at University of Massachusetts, Dartmouth will develop fluorescent sensors for subcellular imaging of free iron ions in live cells. Iron is an essential element for many fundamental physiological processes such as oxygen transport and DNA synthesis. However, free iron is toxic to cells because it promotes the production of highly reactive free radicals which damage biomolecules. Either iron deficiency or iron over-load in the body is linked to various disease conditions.
However, measurement of iron ions in cellular or subcellular compartments is a challenging task due to the lack of analytical techniques with adequate spatial and temporal resolution and sensitivity. In this project "turn-on" and ratiometric fluorescent sensors for subcellular imaging of free iron ions in live cells using a laser confocal microscope will be designed and synthesized. Coordination-induced fluorescence activation (CIFA) or coordination-induced fluorescence resonance energy transfer (CIFRET) mechanisms will be applied to develop the iron-imaging sensors. The sensors will be capable of entering subcellular compartments such as mitochondria to image iron at subcellular level and their ability to image iron ions will be tested in live cells. Insights gained from this study will shed light on the rational design of sensors for imaging other metals and other important biomarkers. This research will provide imaging tools for investigating the complex mechanism of iron homeostasis and iron trafficking at subcellular level, which may potentially lead to the development of pharmaceuticals to treat diseases related to iron dyshomeostasis.
Research will be integrated with educational activities that provide multidisciplinary training of graduate and undergraduate students including women, minority and foreign students and visiting scholars in chemical synthesis and analysis, spectroscopy, microscopy, cell biology and bioimaging. In addition, high school teachers and students will actively participate in the project thus impacting K-12 education in southeastern Massachusetts.