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Project Title:  ORGANA: Oxidation-Reduction potential and Genetic Assessments for New mission Applications Reduce
Images: icon  Fiscal Year: FY 2022 
Division: Space Biology 
Research Discipline/Element:
Space Biology: Cell & Molecular Biology  
Start Date: 01/01/2022  
End Date: 12/31/2023  
Task Last Updated: 04/07/2022 
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Principal Investigator/Affiliation:   Santa Maria, Sergio  Ph.D. / NASA Ames Research Center 
Address:  Space Biosciences Research Branch 
MS 236-7 
Moffett Field , CA 94035 
Phone: 650-604-1411  
Congressional District: 18 
Organization Type: NASA CENTER 
Organization Name: NASA Ames Research Center 
Joint Agency:  
Broddrick, Jared  Ph.D. NASA Ames Research Center 
Gentry, Diana  Ph.D. NASA Ames Research Center 
Liddell, Lauren  Ph.D. NASA Ames Research Center 
Project Information: Grant/Contract No. Internal Project 
Responsible Center: NASA ARC 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2021 Space Biology NNH21ZDA001N-LEIA E.10. Lunar Explorer Instrument for Space Biology Applications 
Grant/Contract No.: Internal Project 
Project Type: GROUND 
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Space Biology Element: (1) Cell & Molecular Biology
Space Biology Cross-Element Discipline: None
Space Biology Special Category: None
Task Description: Space ionizing radiation (IR) and reduced gravity pose risks to long-duration space travel and eventual non-Earth habitation. Given the difficulties in recreating these effects on Earth, developing an in-depth understanding of these risks before sending crewed missions necessitates fully autonomous biological experiments. As an example, BioSentinel is a small satellite with an integrated BioSensor that will measure metabolic and growth changes induced by deep space radiation in the model organism S. cerevisiae (budding yeast). The Lunar Explorer Instrument for Space Biology Applications (LEIA) project is leveraging the same platform to answer biological questions related to lunar exploration.

We hypothesize that both metabolic (redox) and genetic (knockout) assays can distinguish specific changes due to the unique combinations of direct IR damage, indirect oxidative damage, and reduced gravity incurred by exposure to the lunar environment, low Earth orbit (LEO), interplanetary space, and ground-based simulations even before differential survival becomes apparent. These environmental perturbations are known to result in subtle changes in cell growth and activity, but the resulting data is lacking pathway and molecular specificity. By leveraging a metabolic modeling framework and a series of engineered strains, our primary goal is to perform the ground testing necessary to validate strains that yield distinct responses to specific stressors, both laying the groundwork for a potential (and successful) lunar mission to characterize the relative importance of these changes within the capabilities of the BioSensor instrument and improving the usefulness of the alamarBlue assay for past and future missions.

To test our hypothesis, we will pursue the following Specific Aims:

Aim 1: Derive metabolic pathways usage via modeling of a colorimetric assay. The BioSentinel platform uses a redox dye to detect changes in viability and metabolic activity. AlamarBlue changes color in the presence of cell activity and creates intricate time course data that varies as a function of environmental stress, genetic background, and metabolic activity. To date, the rich information in this data has not been connected explicitly to underlying cellular processes. We will combine the data with metabolic modeling to develop a computational tool that extracts detailed metabolic information. This predictive model will not only enable analysis of our experimental design but can be applied to detect changes caused by lunar-like conditions or any autonomous mission that utilizes this reporter dye.

Aim 2: Explore biological effects of a lunar-like environment using DNA repair and stress response defective mutants. Both IR and reduced gravity induce the production of reactive oxygen species (ROS), which play a key role in the generation of cellular and DNA damage, in addition to direct IR damage (e.g., DNA breaks, membrane damage). We will generate yeast mutants defective in DNA repair and stress response pathways, including oxidative damage repair, homologous recombination, and excision repair. Given the short mission duration and the expected low cumulative IR dose, we will also generate mutants containing multiple gene knockouts to increase sensitivity. We will then perform alamarBlue assays after IR exposure in both dry form and in liquid suspension, to study their response.

Aim 3: Engineer endogenous ROS scavenging capabilities in yeast. An indirect effect of IR and cellular stress is the buildup of ROS. While S. cerevisiae has several strategies for ROS removal, we will engineer ROS scavenging mechanisms and evaluate if they can mitigate the unique damage caused by spaceflight stress and IR. We will over-express a native ROS scavenging enzyme and engineer a mannitol biosynthetic pathway, which specifically targets an ROS produced by IR. This aim demonstrates a potential mitigation for future spaceflight missions, enabling insight into how engineered scavenging mechanisms could improve crew safety.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2022 
Task Progress: New project for FY2022.

Bibliography Type: Description: (Last Updated: ) 

Show Cumulative Bibliography Listing
 None in FY 2022