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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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NASA Omics Archive Project

The space environment consists of a complex set of hazards including altered gravity, radiation, psychological/physiological stress, isolation, and confinement leading to complex biological responses. Advances in biotechnology capabilities offer considerable potential to provide novel insight into those responses as well as innovative diagnostic, treatment, and countermeasure solutions for astronauts as NASA begins to travel beyond low Earth orbit. Omics data (genomics, transcriptomics, proteomics, etc.) is one example that can provide NASA with critical knowledge of how a crewmember’s genetics, environment, and lifestyle can be used to develop individualized approaches for disease prevention, advance diagnostics, and improve treatment strategies. NASA ventured into the field of omics on human subjects with the successful completion of the NASA Twins Study which was the first step in mapping the multi-omic profile of astronauts to understand and mitigate the health consequences of spaceflight. The Human Research Program aims to build upon the success of the Twins Study with the NASA Omics Archive flight study, establishing a longitudinal biospecimen archive and efficiently generating a comprehensive high-quality multi-omic dataset from astronauts for the purpose of studying molecular, metabolic, and microbial changes associated with longduration spaceflight missions. The goal is to facilitate scientific and medical research community efforts to characterize and mitigate spaceflight health and performance risks. In this presentation, we will review details regarding the biospecimen and data archive to be generated by the NASA Omics Archive flight study. Data generated as part of this project will be archived in the NASA Life Sciences Portal (NLSP) and be made available for future hypothesis-driven research efforts or occupational surveillance through Institutional Review Board-approved data sharing and retrospective data requests submitted to the Life Sciences Data Archive (LSDA) team. We will also present results of a ground study performed to evaluate in-house procedures, new sample collection hardware, and vendor capabilities. The data repository generated and the samples to be archived by this study will enable future research efforts to assess an astronauts’ unique molecular and genetic profile with respect to individual spaceflight responses. Results of which will be instrumental in enabling precision health capabilities to better assess and mitigate spaceflight risks, detect disease states earlier, and actively monitor countermeasure treatments, ultimately improving clinical outcomes during future exploration class missions.

C. A. Theriot↗
DOE OSTI2022

Characterizing the gene–environment interaction underlying natural morphological variation in Neurospora crassa conidiophores using high-throughput phenomics and transcriptomics

Abstract Neurospora crassa propagates through dissemination of conidia, which develop through specialized structures called conidiophores. Recent work has identified striking variation in conidiophore morphology, using a wild population collection from Louisiana, United States of America to classify 3 distinct phenotypes: Wild-Type, Wrap, and Bulky. Little is known about the impact of these phenotypes on sporulation or germination later in the N. crassa life cycle, or about the genetic variation that underlies them. In this study, we show that conidiophore morphology likely affects colonization capacity of wild N. crassa isolates through both sporulation distance and germination on different carbon sources. We generated and crossed homokaryotic strains belonging to each phenotypic group to more robustly fit a model for and estimate heritability of the complex trait, conidiophore architecture. Our fitted model suggests at least 3 genes and 2 epistatic interactions contribute to conidiophore phenotype, which has an estimated heritability of 0.47. To uncover genes contributing to these phenotypes, we performed RNA-sequencing on mycelia and conidiophores of strains representing each of the 3 phenotypes. Our results show that the Bulky strain had a distinct transcriptional profile from that of Wild-Type and Wrap, exhibiting differential expression patterns in clock-controlled genes (ccgs), the conidiation-specific gene con-6, and genes implicated in metabolism and communication. Combined, these results present novel ecological impacts of and differential gene expression underlying natural conidiophore morphological variation, a complex trait that has not yet been thoroughly explored.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

JGI Plant Gene Atlas: an updateable transcriptome resource to improve functional gene descriptions across the plant kingdom

Abstract Gene functional descriptions offer a crucial line of evidence for candidate genes underlying trait variation. Conversely, plant responses to environmental cues represent important resources to decipher gene function and subsequently provide molecular targets for plant improvement through gene editing. However, biological roles of large proportions of genes across the plant phylogeny are poorly annotated. Here we describe the Joint Genome Institute (JGI) Plant Gene Atlas, an updateable data resource consisting of transcript abundance assays spanning 18 diverse species. To integrate across these diverse genotypes, we analyzed expression profiles, built gene clusters that exhibited tissue/condition specific expression, and tested for transcriptional response to environmental queues. We discovered extensive phylogenetically constrained and condition-specific expression profiles for genes without any previously documented functional annotation. Such conserved expression patterns and tightly co-expressed gene clusters let us assign expression derived additional biological information to 64 495 genes with otherwise unknown functions. The ever-expanding Gene Atlas resource is available at JGI Plant Gene Atlas (https://plantgeneatlas.jgi.doe.gov) and Phytozome (https://phytozome.jgi.doe.gov/), providing bulk access to data and user-specified queries of gene sets. Combined, these web interfaces let users access differentially expressed genes, track orthologs across the Gene Atlas plants, graphically represent co-expressed genes, and visualize gene ontology and pathway enrichments.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Disrupted NOS2 metabolism drives myoblast response to wasting-associated cytokines

Highlights: • Amino acid metabolism is impacted in myoblasts treated with cancer cell conditioned media. • Inflammatory cytokines induce nitric oxide synthase 2 in myoblasts. • Elevated nitric oxide synthase 2 activity impairs myoblast proliferation and differentiation. Skeletal muscle wasting drives negative clinical outcomes and is associated with a spectrum of pathologies including cancer. Cancer cachexia is a multi-factorial syndrome that encompasses skeletal muscle wasting and remains understudied, despite being a frequent and serious co-morbidity. Deviation from the homeostatic balance between breakdown and regeneration leads to muscle wasting disorders, such as cancer cachexia. Muscle stem cells (MuSCs) are the cellular compartment responsible for muscle regeneration, which makes MuSCs an intriguing target in the context of wasting muscle. Molecular studies investigating MuSCs and skeletal muscle wasting largely focus on transcriptional changes, but our group and others propose that metabolic changes are another layer of cellular regulation underlying MuSC dysfunction in cancer cachexia. In the present study, we combined gene expression and non-targeted metabolomic profiling of myoblasts exposed to wasting conditions (cancer cell conditioned media, CC-CM) to derive a more complete picture of the myoblast response to wasting factors. After mapping these features to annotated pathways, we found that more than half of the mapped pathways were amino acid-related, linking global amino acid metabolic disruption to conditioned media-induced myoblast defects. Notably, arginine metabolism was a highly enriched pathway in combined metabolomic and transcriptomic data. Arginine catabolism generates nitric oxide (NO), an important signaling molecule known to have negative effects on mature muscle. We hypothesize that tumor-derived disruptions in Nitric Oxide Synthase (NOS)2-regulated arginine catabolism impair differentiation of MuSCs. The work presented here further investigates the effect of NOS2 overactivity on myoblast proliferation and differentiation. We show that NOS2 inhibition is sufficient to rescue wasting phenotypes associated with inflammatory cytokines. Ultimately, this work provides new insights into MuSC biology and opens up potential therapeutic avenues for addressing disrupted MuSC dynamics in cancer cachexia.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Single cell RNA sequencing reveals shifts in cell maturity and function of endogenous and infiltrating cell types in response to acute intervertebral disc injury

Intervertebral disc (IVD) degeneration contributes to disabling back pain. Degeneration can be initiated by injury and progressively leads to an irreversible loss of cells and function. IVD function restoration through cell replacement therapies have had limited success due to knowledge gaps in the critical cell populations important for repair. Here, in this study, we used single cell RNA sequencing to identify the transcriptional changes of IVD resident and infiltrating cell populations from Control and Injured coccygeal IVDs extracted from 12-week-old female C57BL/6J mice 7 days post injury. Clustering, gene ontology, and pseudotime trajectory analyses determined transcriptomic divergences with injury, flow cytometry identified they types of infiltrating immune cells, and immunofluorescence was utilized to define mesenchymal stem cell (MSC) localization. We identified 11 distinct clusters that included IVD, immune, vascular cells, and MSCs. Differential gene expression analysis determined that Outer Annulus Fibrosus, Neutrophils, Saa2-High MSCs, Macrophages, and Krt18 + Nucleus Pulposus (NP) cells were the major drivers of transcriptomic differences between Control and Injured cells. Gene ontology revealed that the most upregulated biological pathways were angiogenesis and T cell-related while wound healing and ECM regulation were downregulated. Pseudotime trajectory analyses revealed that IVD injury directed cells towards increased differentiation in all clusters, except for Krt18 + NP cells which remained in a less mature cell state. Saa2-High and Grem1-High MSCs populations shifted towards more differentiated IVD cells profiles with injury and localized distinctly within the IVD. This study revealed novel MSC populations with the potential to be leveraged for future IVD repair studies.

Cartilage↗
NASA NTRSDate not supplied

Preparation for and Performance of a Pseudomonas aeruginosa Biofilm Experiment On Board the International Space Station

Biofilms are a problem on Earth given their ability to degrade the materials upon which they grow and due to their relevance to infections. Remarkably, 65% and 80% of infections and chronic diseases on Earth are associated with biofilms, respectively. In space, these problems' impact is higher because the crew's lives and mission success depend on nominal operation of mechanical systems. Furthermore, the isolated confined environment nature of spaceflight may increase the rates of disease transmission. In the case of the International Space Station (ISS), biofilms are an identified problem on the Environmental Control and Life Support System (ECLSS), namely on the water processor assembly (WPA). In late 2019, the Space Biofilms experiment launched towards ISS to (i) characterize the mass, thickness, morphology, and gene expression of biofilms formed in space with respect to matched Earth controls, (ii) interrogate the expression of antimicrobial resistance genes, and (iii) test novel materials as potential biofilm control strategies for future ECLSS components. For this, 288 bacterial samples were prepared prior to the launch of the Northrop Grumman CRS-12 mission from NASA's Wallops Flight Facility. The samples were integrated into the spaceflight hardware, BioServe's Fluid Processing Apparatus (FPA) packed in sets of eight in Group Activation Packs (GAP). Half of these samples were activated and terminated on orbit by NASA astronauts Jessica Meir and Christina Koch, while the remaining half were processed equivalently on Earth. The spaceflight bacterial samples of Space Biofilms returned on board SpaceX' CRS-19 Dragon spacecraft, in early 2020. We here describe the test campaign implemented to verify the experiment design and confirm it would enable us to achieve the project's scientific goals. This campaign ended with the Experiment Verification Test (EVT), from which we here present example morphology and transcriptomic results. We describe in detail the sample preparation prior to flight, including cleaning and sterilization of the coupons of six materials (SS316, passivated-SS316, lubricant impregnated surface, catheter-grade silicone with and without a nanotopography, and cellulose membrane), loading and integration of growth media, bacterial inoculum, fixative and preservative to enable experiment termination on orbit. Additionally, we describe the performance of the experiment on board the ISS, including crew activities, use of assets, temperature profile, and experiment timeline; all leading to a successful spaceflight experiment.

Pamela Flores↗
DOE OSTI2021

Omics-Lethal Human Viruses, West Nile Experiment WCN002

The purpose of this experiment was to evaluate the host response to wild-type West Nile virus (WNV NY99 clone 382) and mutant (WNVE218A) virus infection. Sample data was obtained from mouse cortical neuron tissue and processed for mRNA and miRNA expression analysis. This data set comprises two complete biological replicate experiments conducted in the same conditions and with data processed independently (WCN003). Secondary host-associated viral dataset downloads contain one or more statistically processed (normalization data transformation) quantitative dataset collections resulting in qualitative expression analyses of primary host-pathogen experimental study designs. Transcriptomics dataset downloads have a direct relationship to a primary sample submission corresponding to a specific West Nile virus infection.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Omics-Lethal Human Viruses, West Nile Experiment WCN003

The purpose of this experiment was to evaluate the host response to wild-type West Nile virus (WNV NY99 clone 382) and mutant (WNVE218A) virus infection. Sample data was obtained frommouse cortical neuron tissue for mRNA and miRNA expression analysis. Biological replicate experiments were conducted in the same conditions and with data processed independently (WCN002). Secondary host-associated viral dataset downloads contain one or more statistically processed (normalization data transformation) quantitative dataset collections resulting in qualitative expression analyses of primary host-pathogen experimental study designs. Transcriptomics dataset downloads have a direct relationship to a primary sample submission corresponding to a specific West Nile virus infection.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Omics-Lethal Human Viruses, West Nile Experiment WDC011

The purpose of this experiment was to evaluate the host response to wild-type West Nile virus (WNVMT) and mutant (WNVE218A) virus infection. Sample data was obtained from primary mouse myeloid dendritic cells for mRNA expression analysis. See Experiment WDC010 (GSE74628) for corresponding independent biological replicate study. Secondary host-associated viral dataset downloads contain one or more statistically processed (normalization data transformation) quantitative dataset collections resulting in qualitative expression analyses of primary host-pathogen experimental study designs. Transcriptomics dataset downloads have a direct relationship to a primary sample submission corresponding to a specific West Nile virus infection.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Omics-Lethal Human Viruses, West Nile Experiment WGCN002

The purpose of this experiment was to evaluate the host response to wild-type West Nile virus infectious clone (WNV-NY99 clone 382) and mutant (WNVE218A) virus infection. Sample data was obtained from mouse granule cell neurons for mRNA and miRNA expression analysis. See Experiment WGCN003 for corresponding independent biological replicate study. Secondary host-associated viral dataset downloads contain one or more statistically processed (normalization data transformation) quantitative dataset collections resulting in qualitative expression analyses of primary host-pathogen experimental study designs. Transcriptomics dataset downloads have a direct relationship to a primary sample submission corresponding to a specific West Nile virus infection.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Omics-Lethal Human Viruses, West Nile Experiment WGCN003

The purpose of this experiment was to evaluate the host response to wild-type West Nile virus infectious clone (WNV-NY99 clone 382) and mutant (WNVE218A) virus infection. Sample data was obtained from mouse granule cell neurons for mRNA and miRNA expression analysis. See Experiment WGCN002 for corresponding independent biological replicate study. Secondary host-associated viral dataset downloads contain one or more statistically processed (normalization data transformation) quantitative dataset collections resulting in qualitative expression analyses of primary host-pathogen experimental study designs. Transcriptomics dataset downloads have a direct relationship to a primary sample submission corresponding to a specific West Nile virus infection.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Omics-Lethal Human Viruses, West Nile Experiment WLN002

The purpose of this experiment was to evaluate the host response to wild-type West Nile virus infectious clone (WNV-NY99 clone 382) and mutant WNV-E218A (WNV-NY99 382 E218A 2 nt) virus infection. Sample data was obtained from mouse popliteal draining lymph nodes for mRNA and miRNA expression analysis. See Experiment WLN003 for corresponding omics analysis. Secondary host-associated viral dataset downloads contain one or more statistically processed (normalization data transformation) quantitative dataset collections resulting in qualitative expression analyses of primary host-pathogen experimental study designs. Transcriptomics dataset downloads have a direct relationship to a primary sample submission corresponding to a specific West Nile virus infection.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Poxvirus infection triggers remodeling of host m⁶A epitranscriptome and benefits from the m⁶A regulatory responses

Understanding how host gene regulation responds to viral infection is essential for developing effective antiviral strategies. Emerging evidence suggests that host transcripts undergo dynamic chemical modifications to counteract viral invasion. Conversely, viruses that rely on nuclear transcription exploit host RNA methyltransferases to enhance mRNA export and translation. Orthopoxviruses, however, complete their entire replication cycle within compartmentalized cytoplasmic “factories” utilizing enzymes encoded by their large double-stranded viral DNA genomes. The dynamic interplay between host and poxviral epitranscriptome remains poorly characterized. Using a temporally resolved model of Vaccinia virus (VV) infection, we investigated host-virus interactions through transcriptome and N6-methyladenosine (m⁶A) epitranscriptome whole genome sequencing. We found that host m⁶A modifications respond rapidly to VV infection, preceding the delayed transcriptional changes that emerge at later stages. Early m⁶A signatures included key innate immunity factors as well as host genes involved in transcriptional regulation, post-transcriptional modification, and protein ubiquitination. Functional assays validated two host factors with early m⁶A modification changes that are essential for VV infection: a m⁶A reader, YTHDF1, and a component of the SCF E3 ubiquitin ligase complex, FBXO31. The m⁶A gain on YTHDF1 enhanced its protein expression and promoted efficient VV replication. In addition, we identified previously unrecognized roles of FBXO31 and the SCF E3 ligase complex in supporting VV infection. Temporal profiling of the m⁶A epitranscriptome reveals how VV exploits host post-transcriptional regulatory pathways, specifically m⁶A RNA modification and protein ubiquitination. These findings highlight critical host factors co-opted during poxvirus infection and identify potential targets for therapeutic intervention.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Omics-Lethal Human Viruses, Influenza A Experiment ICL102

The purpose of this experiment was to evaluate the human host cellular response to wild-type Influenza A/Anhui/1/2013 (H7N9; "AH1-WT") virus and mutant viruses NS1-L103F/I106M ("AH1-F/M") and partially ferret-adapted ("AH1-691") infection. Sample data was obtained from human lung adenocarcinoma cells (Calu-3) and processed for mRNA, miRNA, proteomics, lipidomics, and metabolomics expression analysis. Secondary host-associated viral dataset downloads contain one or more statistically processed (normalization data transformation) quantitative dataset collections resulting in qualitative expression analyses of primary host-pathogen experimental study designs. Leveraging unique high-resolution Omics capabilities for proteomics, metabolomics, lipidomics, and transcriptomics dataset download each have a direct relationship to a primary sample submission corresponding to a specific Influenza A virus infection.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Omics-Lethal Human Viruses, Influenza A Experiment ICL103

The purpose of this experiment was to evaluate the human host response to Influenza A wild-type (H5N1) virus and mutant viruses. Sample data was obtained for human lung adenocarcinoma cell line (Calu-3) infected with WT Influenza A/Vietnam/1203/2004 (H5N1, VN1203) and mutant viruses PB2-K627E and NS1-trunc124 for mRNA, miRNA, proteomics, lipidomics, and metabolomics data analysis. Secondary host-associated viral dataset downloads contain one or more statistically processed (normalization data transformation) quantitative dataset collections resulting in qualitative expression analyses of primary host-pathogen experimental study designs. Leveraging unique high-resolution Omics capabilities for proteomics, metabolomics, lipidomics, and transcriptomics dataset download each have a direct relationship to a primary sample submission corresponding to a specific Influenza A virus infection.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Omics-Lethal Human Viruses, Influenza A Experiment ICL104

The purpose of this experiment was to evaluate the host response to Influenza A pandemic wild-type H1N1 (A/California/04/2009), natural isolate virus. Sample data was obtained from human lung adenocarcinoma cells (Calu-3) with wild-type H1N1 virus (A/California/04/2009) and processed for mRNA, miRNA, proteomics, metabolomics, and lipidomics expression analysis. Secondary host-associated viral dataset downloads contain one or more statistically processed (normalization data transformation) quantitative dataset collections resulting in qualitative expression analyses of primary host-pathogen experimental study designs. Leveraging unique high-resolution Omics capabilities for proteomics, metabolomics, lipidomics, and transcriptomics dataset download each have a direct relationship to a primary sample submission corresponding to a specific Influenza A virus infection.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Omics-Lethal Human Viruses, Interferon-Stimulated Response Experiment IFNFB001

The purpose of this experiment was to evaluate the human host cellular response to interferon alpha/beta (IFNα/β) or interferon gamma (IFNγ) treatment. Sample data was obtained from primary human lung fibroblast (FB) cells inoculated with IFNα/β or IFNγ for transcriptome analysis. Secondary host-associated viral dataset downloads contain one or more statistically processed (normalization data transformation) quantitative dataset collections resulting in qualitative expression analyses of primary host-pathogen experimental study designs. Transcriptomics dataset download have a direct relationship to a primary sample submission corresponding to a specific interferon response to viral infection.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Omics-Lethal Human Viruses, Interferon-Stimulated Response Experiment IFNMVE001

The purpose of this experiment was to evaluate the human host interferon-stimulated cellular response to interferon alpha/beta (IFNα/β) or gamma (INFγ) treatment. Sample data was obtained from primary lung microvascular endothelial cells (MVE) treated with or without human IFNαβ or INFγ for mRNA transcriptome expression analysis. Secondary host-associated viral dataset downloads contain one or more statistically processed (normalization data transformation) quantitative dataset collections resulting in qualitative expression analyses of primary host-pathogen experimental study designs. Transcriptomics dataset download have a direct relationship to a primary sample submission corresponding to a specific interferon response to viral infection.

59 BASIC BIOLOGICAL SCIENCES↗