Nanoprobes for imaging single cells under low -dose radiation

The objective of this Glue Grant proposal is to conduct fundamental research for the development of unique optical nanoprobes forimaging single cells to monitor reactive oxygen species (ROS) under low-dose ionizing radiation (IR). The biological consequences ofan organism's response to low-dose radiation that might exceed the background level of oxidative damage to a cell in a tissue couldbe apoptosis, cell proliferation, or cell differentiation. There is physical and chemical evidence that ROS are involved in primarypathological events produced by IR in the cell. Advances in techniques to measure quantitatively the earlyevents associated withirradiation of cells are crucial to understanding molecular mechanism, and are currently lacking. To address this deficiency wepropose to develop nanoscale sensors that will measure the early intracellular biochemical events such as ROS formation uponexposure to low doses or low fluences of ionizing radiation, specifically changes in hydrogen peroxide and related signalingpathways, in real time and with quantitative detection. These sensors will be based on the radiobiological principle that much ofthe damage from IR results from ROS formation, and that measuring ROS and/or indices of ox-redox status within a cell willreflect its level of IR insult. The strategy will be further expanded to investigate intracellular ROS occurring in unirradiatedcells caused by a so-called "bystander" effect. Our approach will directly investigate the molecular mechanisms that are involved inthe generation of ROS in single cells, and will also shed light on the characterization of radiation-induced bystander effects incell monolayers or tissue-like models. This Glue Grant will mainly fund a postdoctoral associate to support collaborative workbetween two laboratories.Keywords: nanoprobe, single cell imaging, bystander effect, low-dose radiation, reactive oxygen species