ALBERT

Description: NASAs PowerCell payload on the DLR (Deutsches Zentrum fur Luft- und Raumfahrt, i.e. German Aerospace Center) Eu:CROPIS satellite will compare the effect of multiple simulated gravity regimes on basic processes required for synthetic biology in space including growth, protein production, and genetic transformation of the bacterium Bacillus subtilis. In addition, it will pioneer the use of a cyanobacterially-produced feedstock for microbial growth in space, a concept we call PowerCell. The PowerCell experiment system will be integrated using the Spaceflight Secondary Payload System with the German Space Agency's (DLR's) Euglena and Combined Regenerative Organic-food Production In Space (Eu:CROPIS) satellite, to be launched during the summer of 2017. In order to simulate the gravitational gradient of different celestial bodies, the Eu:CROPIS satellite will establish artificial microgravity, lunar, and Martian gravity levels prior to conducting each set of biological experiments, with experimental results compared to ground controls. Experiments will be carried out in microfluidics cards with experimental progress measured through absorbance as detected by the LED-based optical system. Here we describe the ground studies that led to these experiments, along with a description of the flight hardware and its performance. The results of this mission will provide foundational data for the use and production of genetically engineered organisms for extraterrestrial missions.

Description: High-LET ionizing radiation is a major occupational health hazard for astronauts, but risk assessment remains elusive due to limited epidemiological data. Identifying genetic factors modulating the individual radiation response may be the most effective strategy to provide individualized risk management for long-duration high-radiation missions. We have started tackling the challenge of predicting individual risks by identifying human genetic loci associated with various radiation sensitivity phenotypes in primary blood mononuclear cells from a relatively large healthy human cohort. To date, we have performed the isolation of PBMCs from 768 subjects of the same ethnicity, and irradiated PBMCs from 576 subjects with 1 and 3 particles/100m2 of 600 MeV/n 56Fe, 350 MeV/n 40Ar and 350 MeV/n 28Si ions. The phenotypes of interest were: number of radiation-induced foci (or RIFs), CellROX oxidative stress responses and cell death, at 4h and 24h following irradiation. We have observed a significant inter-individual variability at 0 Gy between the 576 studied subjects, with a mean fold difference between the 10% lowest and highest responders of 5.6 of RIFs/cell, 7.9 in mean CellRox intensity, and 9.3 in percentage of dead cells. In order to better assess genetic factors influencing DNA repair, we used a metric previously introduced by our group to sort out radiation sensitivity phenotypes in mice: i.e. the ratio of the first to the second slope of RIFs/cell (between 0 and 1, and between 1 and 3 particle/100m2). Preliminary data on 192 individuals showed a distribution of low-dose responders (ratio 〉 1) to high-dose responders (ratio 〈 1) at 4h of 12%, 55% and 52% respectively for Fe, Ar and Si. The average value for the first and the second slopes was very similar for the two lowest LET (0.10 [-0.26;0.58] and 0.09 [-0.45;0.41] for Ar, 0.07 [-0.27;0.38] and 0.08 [-0.19;0.42] for Si), indicating a linear dose response across both fluence. Fe showed clear saturation for the highest dose with a slope of -0.09 [-0.86;1.51] against 0.68 [-2.21;2.20] for the low dose range, which probably reflects that many PBMCs are beyond repair at the high dose. Note that other significances were found for additional factors such as BMI and age whereas none were found for sex. GWAS will be performed on all phenotypes upon completion of measurements.

Description: High-LET ionizing radiation is a major occupational health hazard for astronauts, but risk assessment remains elusive due to limited epidemiological data. Identifying genetic factors modulating the individual radiation response may be the most effective strategy to provide individualized risk management for long-duration high-radiation missions. We have started tackling the challenge of predicting individual risks by identifying human genetic loci associated with various radiation sensitivity phenotypes in primary blood mononuclear cells from a relatively large healthy human cohort. To date, we have performed the isolation of PBMCs from 768 subjects of the same ethnicity, and irradiated PBMCs from 576 subjects with 1 and 3 particles/100m2 of 600 MeV/n 56Fe, 350 MeV/n 40Ar and 350 MeV/n 28Si ions. The phenotypes of interest were: number of radiation-induced foci (or RIFs), CellROX oxidative stress responses and cell death, at 4h and 24h following irradiation. We have observed a significant inter-individual variability at 0 Gy between the 576 studied subjects, with a mean fold difference between the 10% lowest and highest responders of 5.6 of RIFs/cell, 7.9 in mean CellRox intensity, and 9.3 in percentage of dead cells. In order to better assess genetic factors influencing DNA repair, we used a metric previously introduced by our group to sort out radiation sensitivity phenotypes in mice: i.e. the ratio of the first to the second slope of RIFs/cell (between 0 and 1, and between 1 and 3 particle/100m2). Preliminary data on 192 individuals showed a distribution of ?low-dose responders? (ratio 〉 1) to ?high-dose responders? (ratio 〈 1) at 4h of 12%, 55% and 52% respectively for Fe, Ar and Si. The average value for the first and the second slopes was very similar for the two lowest LET (0.10 [-0.26;0.58] and 0.09 [-0.45;0.41] for Ar, 0.07 [-0.27;0.38] and 0.08 [-0.19;0.42] for Si), indicating a linear dose response across both fluence. Fe showed clear saturation for the highest dose with a slope of -0.09 [-0.86;1.51] against 0.68 [-2.21;2.20] for the low dose range, which probably reflects that many PBMCs are beyond repair at the high dose. Note that other significances were found for additional factors ? such as BMI and age ? whereas none were found for sex. GWAS will be performed on all phenotypes upon completion of measurements.