BioNutrients: Microbial On-Demand Production of Short Shelf-Life Micronutrients in Space
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Engineering topics
Publications and source records attributed to Natalie Nicole Ball.
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Radiation and reduced gravity pose biological risks to crewed deep space exploration. At the cellular level, radiation damage can be amplified by reduced gravity. Empirical evidence on cellular responses to beyond low Earth orbit (BLEO) environments is imperative to develop effective countermeasures for crew health and in-space biomanufacturing. The Lunar Explorer Instrument for Space Biology Applications (LEIA) project is developing an instrument suite to be delivered to the south polar region of the Moon by the Commercial Lunar Payload Services (CLPS) program. This presentation will provide an overview of the LEIA hardware, experiments, and mission timeline. The LEIA instruments include the BioSensor, the ARES charged particle detector, and the Mini-FND. The BioSensor is an autonomous light emitting diode (LED)-based spectrophotometer and microfluidic incubator. The BioSensor activates yeast cultures and can measure cell growth, metabolic activity, and carotenoid production. The ARES is a Timepix-based charged particle radiation detector that measures dose, dose rate, and linear energy transfer spectra. The Mini-FND is a fast neutron detector that measures albedo neutron flux and energy spectra. Combined, these instruments will be used for yeast genetics experiments to quantify growth, metabolism, and synthetic biology-enabled production of human nutrients, while taking real time measurements of biologically relevant radiation exposure on the lunar surface. These data will be used to test the importance of selected DNA damage repair and reactive oxygen species defense pathways in mitigating cellular damage from lunar surface radiation.
With sights set on returning a human presence to the Moon and plans to explore even farther beyond, it is imperative we understand the impact of deep space radiation, partial gravity, and the lunar surface on biology. The need for countermeasures to protect future astronauts from the unique conditions of space is ever-pressing and an assessment of bioproduction capabilities in space is a crucial step for sustaining long-term missions. The Lunar Explorer Instrument for space biology Applications (LEIA) aims to investigate the cell’s response to the lunar environment and test strategies for enhancing cellular tolerance on the Moon, utilizing the budding yeast Saccharomyces cerevisiae as a biosensor. S. cerevisiae serves as an excellent model organism due to its widespread use as an analog for human cells, well-characterized set of genetic tools, and ability to survive desiccation. However, these cells must remain desiccated for up to one year prior to launch and the radiation-sensitive strains designed for LEIA will likely be more vulnerable to desiccation effects. In this work, we introduce tardigrade proteins known for their protective mechanisms into potential LEIA strains to test genetic strategies for improving desiccation and radiation tolerance. Tardigrades are extremotolerant animals well-known for their ability to survive in harsh environments. Notably, they can survive extreme desiccation and radiation due to the upregulation of intrinsically disordered proteins (IDPs). It has been shown that integration of these tardigrade IDPs, such as cytosolic abundant heat-soluble (CAHS) proteins, into yeast can confer increased desiccation tolerance in synergy with trehalose. Our ongoing testing and assessment of bioengineered radiation and desiccation tolerance will help us gain insight into optimizing strain design and selection for protecting LEIA’s biological payload as well as genetic engineering strategies for enhancing bioproduction potential for future missions beyond low Earth orbit.
Biomanufacturing can provide on-demand production of mission-critical compounds and materials to support long-duration space exploration while circumventing the challenges of transporting materials from Earth. Synthetic Biology Project is developing two biomanufacturing capabilities: BioNutrients and CO2-Based Manufacturing. BioNutrients is an ongoing mission aboard the International Space Station focused on the production of perishable nutrients in an on demand for direct for consumption. The first flight experiment of this project targeted the production of carotenoids: β-carotene and zeaxanthin, in recombinant yeast strains. Since then, the project has expanded to encompass the production of the fermented consumables like yogurt and kefir for use as a nutrient delivery mechanism. The CO2-Based Manufacturing system aims to use in situ resources to allow for biomanufacturing with minimal re-supply required. The manufacturing platform is combined with an electrochemical CO2 conversion system which can produce simple carbon substrates to support microbial based biomanufacturing. A comprehensive ground-based platform for recombinant protein purification is in development with the goal of producing a thermostable carbonic anhydrase enzyme from E. coli utilizing CO2-derived acetate. Our group hopes to propel advancements in space biomanufacturing for long duration space flight by harnessing the tools of synthetic biology.