David Marshall Porterfield

Space biology literature is growing exponentially. Existing infrastructure has not kept pace with organizing, synthesizing, and disseminating this knowledge. We present SpaceBio SpaceBio Knowledge Hub ( www.spacebio.space ), an integrated digital ecosystem that combines artificial intelligence, real-time data integration, and open-access infrastructure to advance research, education, and collaboration in microgravity, space biology and space exploration. The platform applies AI-driven approaches including natural language processing, machine learning, and automated content generation to construct a semantic atlas of the field. The atlas reveals the hierarchical thematic organization underlying microgravity-induced biological responses, space mission infrastructure, planetary science, and astrobiology. As part of this effort, SpaceBio is moving toward the construction of a LiteratOmics framework for microgravity, and space biology a systematic, AI-enabled approach to mining, integrating, and structuring the primary literature generated by omics-driven spaceflight research, treating the scientific literature itself as a navigable data layer alongside genomic, transcriptomic, and proteomic datasets. Built on a scalable, cloud-based architecture with a user-centered interface, SpaceBio supports literature exploration, data integration, and knowledge discovery for researchers, educators, students, industry partners, and citizen scientists. The platform also functions as a community-building ecosystem. It integrates hands-on research initiatives, AI-generated educational content, pilot data science projects, and social responsibility programs that broaden participation without compromising scientific rigor. AI-enabled digital environments can transform fragmented literature into a navigable knowledge landscape. SpaceBio accelerates research productivity, strengthens STEM education, and supports the global space life sciences community as human space exploration enters in the most ambitious era.

Mycoponic biotechnology, inspired by hydroponics—a vital technology for agriculture research and space exploration, is limited by innate substrate contamination commonplace in commercial mycoproduction. Using micro‐structured ceramic tubes as “substrate,” mycoponics provides mycelial cellular filaments with an air‐phase/solid‐state, antimicrobial interface for cellular liquid nutrient media uptake. We show how antimicrobial biophysical size exclusion facilitates mycoponic “persistent‐filtration‐defense” (PFD), experimentally confirmed using flow cytometry, and electron microscopic analysis of the interfacial ceramic pores (less than 300 nm). The antimicrobial mycoponic interface enabled development of a complete mycoponic nutrient medium, producing blue oyster mushrooms from liquid culture 2 weeks post inoculation. This completely eliminates grain‐spawn (2–4 weeks) and fruiting phase (2–4 weeks) times using granular substrate bags that require energy/time‐intensive antimicrobial processing. Mycelial colonization times decreased by 9 days, while biomass increased (170%) with activated carbon inside the tubes. Mycoponic cultivation of Reishi mycoleather gloves demonstrates direct 3D‐mycomaterials, and we show how mycoponics enables advanced scientific imaging (thermal) and techniques, including mycelial exudate recovery for drug discovery. Mycoponics enables hybrid solid‐state, liquid culture for continuous bioproduction of mycelial pharmaceuticals, representing 18% of the global market. The efficiency and extended cultivation enabled by mycoponics will facilitate significant future advances in mycology and mycoengineering.

A major requirement for humans is a breathable atmosphere for adequate respiratory CO ₂ /O ₂ gas exchange. In microgravity, despite environmental life support systems regulating air exchange, astronauts complain about air quality, with elevated CO ₂ -levels resulting in detrimental health and performance effects. Using high-fidelity computational fluid dynamics, we create a model of human respiratory ventilation to show how gravity biophysically shapes and drives respiratory exchange on Earth and in microgravity. On Earth, gravity influences gas exchange through buoyancy and biothermal convection, generating a ‘human thermal body plume’ that drives airflow around the human body, and so facilitates effective gas exchange. We show that the absence of biothermal convection in microgravity reduces this airflow around the human body. This impairs gas exchange by creating an environmental breathing deadspace immediately in front of the face, leading to significant CO ₂ -rebreathing, with direct implications for astronaut health and countermeasures. This model was also used to estimate engineering requirements for directed external airflow equivalent to that generated by the human thermal body plume to alleviate this problem. Our model further shows that in Earth-normal 1 g, increasing ambient air temperature can also reduce efficient respiratory exchange, resulting in breathing conditions equivalent to those in microgravity, with implications for respiratory health on Earth.

A major requirement for humans is a breathable atmosphere for adequate respiratory CO2/O2 gas exchange. In microgravity, despite environmental life support systems regulating air exchange, astronauts complain about air quality, with elevated CO2-levels resulting in detrimental health and performance effects. Using high-fidelity computational fluid dynamics, we create a model of human respiratory ventilation to show how gravity biophysically shapes and drives respiratory exchange on Earth and in microgravity. On Earth, gravity influences gas exchange through buoyancy and biothermal convection, generating a ‘human thermal body plume’ that drives airflow around the human body and so facilitates effective gas exchange. We show that the absence of biothermal convection (in microgravity or high temperatures) reduces this fresh air exchange around the human body by creating environmental hypercapnia immediately in front of the face, and significant CO2-rebreathing with direct implications for astronaut health and countermeasures. The scientific model for the HTBP was used to estimate the engineering requirements for directed external airflow equivalents, as a countermeasure for IBD induced hypercapnia in spaceflight. Our model also links terrestrial hyperthermia and heat stress to hypercapnic induced cardiovascular respiratory events. Climate associated increase in ambient air temperatures can also reduce efficient respiratory exchange with implications for respiratory health on Earth, and synergistic stress effects in microgravity.

NASA and the CNSA have both released plans for lunar human exploration. This paper reviews those plans through the lens of strategic capability development. It examines the history of NASA’s development of bioregenerative space habitation systems and shows how past research and policy decisions, including funding cuts and program discontinuations, have led to critical gaps in current NASA capabilities. These gaps pose a strategic risk to US leadership in human space exploration that must be addressed urgently to sustain international competitiveness. It concludes with recommendations for program investments crucial for the deployment of mature bioregenerative technologies in the coming decade.

Graviresponses, the growth responses of organisms to gravitational alterations, are pivotal yet understudied phenomena in fungi compared to plants and animals. Fungi perceive gravity through proposed statoliths, including nuclei connected to actin filaments, octahedral protein crystals, and floating lipid globules. These mechanisms generate sufficient potential energy to overcome thermal noise and establish detectable gradients within cells. Signal transduction involves ion fluxes, reactive oxygen species, and cytoskeletal components, transducing physical signals into polarised cell wall loosening. In mushroom-forming fungi, gravitropic responses manifest primarily through differential hyphal elongation in the stipe, while gravimorphogenetic responses cause broader developmental and morphological changes. Though basic fruiting body formation can occur in microgravity, proper spore dispersal requires gravity sensing which triggers molecular mechanisms involving precise regulation of cell wall modification, vesicle trafficking, and complex signalling cascades, particularly in specialised tissues of the fruiting body. Curvature compensation mechanisms ensure optimal vertical alignment of spore-bearing tissues through feedback systems. Studies of model organisms like Coprinopsis cinerea, Flammulina velutipes, and Phycomyces blakesleeanus have revealed species-specific gravisensing mechanisms that reflect diverse ecological strategies for spore dispersal. Despite advances in understanding these mechanisms, key questions remain about morphogenetic regulation and signal transduction. This review examines classical and modern findings while highlighting opportunities for investigation using contemporary molecular approaches.

SUMMARY: Understanding the dynamic adaptive plasticity of microorganisms has been advanced by studying their responses to extreme environments. Spaceflight research platforms provide a unique opportunity to study microbial characteristics in new extreme adaptational modes, including sustained exposure to reduced forces of gravity and associated low fluid shear force conditions. Under these conditions, unexpected microbial responses occur, including alterations in virulence, antibiotic and stress resistance, biofilm formation, metabolism, motility, and gene expression, which are not observed using conventional experimental approaches. Here, we review biological and physical mechanisms that regulate microbial responses to spaceflight and spaceflight analog environments from both the microbe and host-microbe perspective that are relevant to human health and habitat sustainability. We highlight instrumentation and technology used in spaceflight microbiology experiments, their limitations, and advances necessary to enable next-generation research. As spaceflight experiments are relatively rare, we discuss ground-based analogs that mimic aspects of microbial responses to reduced gravity in spaceflight, including those that reduce mechanical forces of fluid flow over cell surfaces which also simulate conditions encountered by microorganisms during their terrestrial lifecycles. As spaceflight mission durations increase with traditional astronauts and commercial space programs send civilian crews with underlying health conditions, microorganisms will continue to play increasingly critical roles in health and habitat sustainability, thus defining a new dimension of occupational health. The ability of microorganisms to adapt, survive, and evolve in the spaceflight environment is important for future human space endeavors and provides opportunities for innovative biological and technological advances to benefit life on Earth.

Our previous research revealed a key microRNA signature that is associated with spaceflight that can be used as a biomarker and to develop countermeasure treatments to mitigate the damage caused by space radiation. Here, we expand on this work to determine the biological factors rescued by the countermeasure treatment. We performed RNA-sequencing and transcriptomic analysis on 3D microvessel cell cultures exposed to simulated deep space radiation (0.5 Gy of Galactic Cosmic Radiation) with and without the antagonists to three microRNAs: miR-16-5p, miR-125b-5p, and let-7a-5p (i.e., antagomirs). Significant reduction of inflammation and DNA double strand breaks (DSBs) activity and rescue of mitochondria functions are observed after antagomir treatment. Using data from astronaut participants in the NASA Twin Study, Inspiration4, and JAXA missions, we reveal the genes and pathways implicated in the action of these antagomirs are altered in humans. Our findings indicate a countermeasure strategy that can potentially be utilized by astronauts in spaceflight missions to mitigate space radiation damage.