Thrust 1: Radiation and Microgravity Research Thrust

Investigators: Drs. Saleh, Abdel-Rahman, Ramesh, Shishodia, Fox, Ford, Briggs, Jejelowo

Astronauts on space flight are exposed both to radiation and microgravity. The combined action of ionizing radiation and microgravity will continue to influence future manned space missions, with special risks for astronauts on the Moon surface or long duration missions to Mars. There is increasing evidence that basic cellular functions are sensitive not only to radiation, but also to microgravity. Previous space flight experiments gave contradictory results, ranging from inhibition to enhancement of DNA repair by microgravity, and from both synergistic or antagonistic. Alterations in response to microgravity have been reported on the molecular, cellular, and systemic levels. This project will further study the effects of microgravity changes and radiation at the genome, proteome, cell, tissue, organ, and organismal levels. We will identify biomarkers of stress factors along the various biological levels of organization and develop countermeasures to the stress effects. This project aims to 1) investigate the simultaneous effect of radiation and microgravity using model cells and organisms, and 2) develop countermeasures for the effects of radiation and microgravity

Objective 1.To monitor the effects of radiation and microgravity, model organisms are used assess antibiotic and stress resistance, changes in gene expression, and DNA damage. C. elegans will be examined for genotoxicity and changes in lifespan and behavior. Cells and mice will be monitored for altered NFkB activation, epigenetic changes, production of reactive oxygen/nitrogen species (ROS/RNS), alterations in redox-sensitive signaling and transcription, and accumulation of DNA damage. This will involve the use of the NASA-developed High Aspect Rotating Vessel (HARV) bioreactor to produce a unique Low-Shear Modeled Microgravity (LSMMG) environment.

Strategy 1: Using bacteria as a model to investigate the effects of radiation and/or microgravity.

Strategy 2: Using C. elegans as a model to investigate the effects of radiation and/or microgravity on organismal health.

Strategy 3: Use of mammalian cell culture and whole organisms to further understand the effects of radiation and microgravity.

Objective 2. To develop countermeasures for the effects of radiation and microgravity. We are testing a variety of compounds in an attempt to prevent the damage caused by radiation and microgravity, including antixodants, curcumin and resveratrol, and various other natural products. The assays developed in Objective 1 will be utilized to determine if these treatments prevent such damage.

Strategy 1: Antioxidants to counteract the effects of space on C. elegans.

Strategy 2: Use of curcumin and resveratrol to counteract radiation and microgravity-induced NF-kB activation.

Strategy 3: Use of natural products to counteract radiation and microgravity-induced epigenetic changes.

Strategy 4: Use of antioxidants/natural products to block the effects of ROS/RNS generated by radiation and microgravity.