Understanding molecular mechanisms associated with exposure to low and ultra low doses of ionizing radiation.

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This Discovery Grant renewal application is part of an ongoing program investigating mechanisms of cellular responses to low doses of ionizing radiation exposure. This proposal has the specific aim to focus on cellular response mechanisms to levels of ultra-low radiation doses by selectively removing various radiation types of natural background radiation (cosmic rays, alpha from radon, and terrestrial external gamma photons). Using modern biological endpoints well established in our laboratory, we will seek to understand the notion that natural background radiation is essential for life. In the absence of natural background radiation and consequent free radical stress, we hypothesize that cellular systems may falter. Ionizing radiation comes from natural (cosmic and terrestrial) and manmade (medicine and energy) sources. Living organisms may be exposed to low doses of natural and manmade sources and a better understanding of the biological mechanisms associated with low dose exposures is valuable. It is well known that high doses of ionizing radiation produce reactive oxygen species and oxidative stress which can be damaging to cells. However, at low doses, radiation can induce an evolutionary conserved adaptive response that may protect cells by maintaining and activating cellular defense mechanisms. Humans are preparing to return to the moon in 2024 and then onward to Mars. In space, galactic cosmic radiation is ionizing radiation which causes damage to biological life, e.g. astronauts. We are collaborating NASA scientists on several projects aimed at understanding the consequences of space radiation exposure and possible countermeasures to protect organisms from the damage. One of the projects is BioSentinel which is a NASA Ames Research Center astrobiology research project that aims to detect and measure the impact of deep space radiation on living organisms. The BioSentinel project is currently utilizing genetically modified mutants of the yeast Saccharomyces cerevisiae as a biosensor model to study the effects of galactic cosmic radiation in deep space (40,000,000 km) on DNA damage and repair. Currently, we are characterizing the BioSentinel model yeast strains in our lab on the earth surface and in our new novel life sciences SNOLAB research laboratory 2km (6,800 ft) underground. The rock burden above SNOLAB eliminates virtually all galactic cosmic radiation. Specialized shielding within the SNOLAB eliminates external terrestrial gamma radiation emanating from the rock walls, and an innovative growth chamber eliminates naturally occurring radioactive radon gas. Consequently, we can test the hypothesis that background radiation modulates biological processes and may be an essential component of life. The research will help us understand how some biological processes may be critical to protect humans and other life forms from galactic cosmic radiation while travelling in space.