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At least 253 records · Page 14
All sourcesNASA NTRSDOE OSTI
NASA NTRSDate not supplied

Murine Host-gut Microbiota Interactions are Modulated During Spaceflight

The rodent habitat on the International Space Station has provided critical insight into the impact of spaceflight on mammalian physiology. These effects include dysfunction of carbohydrate, steroid and lipid metabolism, and immune response, as well as induction of symptoms characteristic of liver disease, insulin resistance, osteopenia and myopathy, which are anticipated to intensify over long-duration spaceflight. Although these physiological responses can involve the microbiome, the host-microorganism interactions during spaceflight are still largely unknown. NASA GeneLab curates a wide range of space research data and the current work harnesses GeneLab multi’omic data from recent Rodent Research studies to explore changes to gut microbiota during spaceflight and their associations with host physiology when compared to ground controls. Using a hybrid analysis of DNA barcoding and whole genome shotgun data, an array of bacteria, fungi and nematodes could be identified at species level, and significant differences in relative abundances associated with spaceflight. Functional prediction based on differential abundance of species and metagenome gene inventories as well as metatranscriptomic gene expression at the host-gut microbiome interface implicate microbiota interactions could contribute to spaceflight pathology. Harnessing carefully curated publicly available data, such as from Genelab, to generate multi‘omic space science discoveries can help decipher the complex host-microbiome interactions that influence both health on Earth and the feasibility of long-duration spaceflight.

Microbiome↗
NASA NTRSDate not supplied

Conclusions of A Mini Technical Interchange Meeting on New Cross Risk Integration Projects Managed By the NASA Space Radiation Element

To enable deep space exploration and sustained human presence in space, the NASA Human Research Program’s (HRP) Space Radiation Element (SRE) funds research to characterize and mitigate adverse health outcomes from exposure to space radiation. Recently, the Space Radiation Element was tasked with supporting multiple HRP Elements with innovative and enabling projects to inform risk characterization, facilitate mitigation activities, and support crew health and performance. These projects, such as precision health initiative, NASA Omics Archive (NOA) and human sample repositories, are agnostic to any HRP Element, hence the name, Cross Risk Integration Projects (CRIP). CRIP serves three broad purposes: Services: Generate samples/data or manage the receipt, inventory, archive and ultimate redistribution of biospecimens created in HRP-funded spaceflight and analog research activities – includes NASA Omics Archive (NOA) project and various human and animal sample repositories. Method Development: Identify and evaluate, new-to-NASA research or analysis methods or techniques – includes TRRaC (Translational Radiation Research and Countermeasures) Project. Enabling Capabilities: Demonstrate real world application by adapting, adopting and/or developing capabilities to benefit crew health & performance and improve risk – includes Precision Health Initiative (Pharmacogenomics) and advanced biological systems and engineered tissue microsystems initiative (tissue chips, organ-on-a-chip). To identify new technologies, future work, and solicitations, the SRE organizes themed sessions at annual HRP Investigators’ Workshops (IWS). These technical interchange meetings (TIMs) provide a venue for the scientific community to present ongoing work and engage in open discussion, limitations of current approaches, and incorporation of novel experimental strategies and other innovative techniques. Here a summary and lessons learned from the SRE-sponsored mini-TIM titled “Space Radiation Cross Risk Integrations Projects” at HRP IWS 2024 will be communicated. The 90-min TIM had 6 speakers who presented impressive novel ideas and work This poster presents the outcomes of the session along with proposed future workshops and other SRE initiatives.

Janapriya Saha↗
NASA NTRS2024

Conclusions of a Mini Technical Interchange Meeting on New Cross Risk Integration Projects Managed by the NASA Space Radiation Element

To enable deep space exploration and sustained human presence in space, the NASA Human Research Program’s (HRP) Space Radiation Element (SRE) funds research to characterize and mitigate adverse health outcomes from exposure to space radiation that include risks of carcinogenesis, cardiovascular disease, and central nervous system decrements. Recently, the SRE was tasked with supporting multiple HRP Elements with innovative and enabling projects to inform risk characterization, facilitate mitigation activities, and support crew health and performance. These projects, such as precision health initiative, NASA Omics Archive (NOA) and human sample repositories, are agnostic to any HRP Element, hence the name, Cross-Risk Integration Projects (CRIP). CRIP serves 3 broad purposes: - Services: Generate samples and data and manage the receipt, inventory, archive, and ultimate redistribution of biospecimens created in HRP-funded spaceflight and analog research activities—includes NASA Omics Archive project and various human and animal sample repositories. - Method Development: Identify and evaluate new-to-NASA research or analysis methods or techniques that could fundamentally improve existing or planned research efforts—includes the Translational Radiation Research and Countermeasures Project. - Enabling Capabilities: Demonstrate real-world application by adapting, adopting, and/or developing capabilities to benefit crew health and performance and improve risk mitigation—includes Precision Health Initiative (Pharmacogenomics) and advanced biological systems and engineered tissue microsystems initiative (tissue chips, organ-on-a-chip). To identify new technologies, future work, and solicitations, the SRE organizes themed sessions at annual HRP Investigators’ Workshops (IWS). These technical interchange meetings (TIMs) provide a venue for the scientific community to present ongoing work and engage in open discussion of results, limitations of current approaches, and incorporation of novel experimental strategies, model systems, and other innovative techniques. Here, a summary of the studies presented at the SRE-sponsored mini-TIM at the HRP IWS along with the goals and objectives of the CRIP projects is communicated. The 90-min TIM had 6 speakers who presented impressive novel ideas and work, some of which are funded under CRIP by the Space Radiation Element.

Janapriya Saha↗
DOE OSTI2024

Exploring new frontiers in type 1 diabetes through advanced mass-spectrometry-based molecular measurements

Type 1 diabetes (T1D) is a devastating autoimmune disease for which advanced mass spectrometry (MS) methods are increasingly used to identify new biomarkers and better understand underlying mechanisms. For example, integration of MS analysis and machine learning has identified multimolecular biomarker panels. In mechanistic studies, MS has contributed to the discovery of neoepitopes, and pathways involved in disease development and identifying therapeutic targets. However, challenges remain in understanding the role of tissue microenvironments, spatial heterogeneity, and environmental factors in disease pathogenesis. Recent advancements in MS, such as ultra-fast ion-mobility separations, and single-cell and spatial omics, can play a central role in addressing these challenges. Here, in this work, we review recent advancements in MS-based molecular measurements and their role in understanding T1D.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Challenges in spatial metabolomics and proteomics for functional tissue unit and single-cell resolution

While transcriptomics is the most broadly applied technology for global spatial and single cell measurements in healthy and diseased tissues. Transcripts are often used as a proxy for protein and even metabolite measurements, but it has become commonly accepted that extrapolating this kind of information is a poor proxy and not a substitute for direct measurement. Within the last decade advanced developments of mass spectrometry-based assays have made these direct measurements not only possible, but routine. Where mass spectrometry has become an enabling technology, and various methods can now detect hundreds of metabolites and thousands of proteins from samples. Not only can this be performed within bulk measurements, but much effort has been directed into translating these measurements to single cells and tissues at cellular resolution. The information obtained from mass spectrometry is now able to trace metabolic events and decipher feedback loops across anatomical regions, connecting genetic and metabolic networks that define phenotypes. Herein, we will broadly overview developments in the field over the past decade, leading into several case studies which highlight the direct measurement of metabolites, proteins, and proteoforms from thinly sliced tissues. Much of this work is feasible due to multidisciplinary team science, and we offer brief perspective on paths forward and the challenges that persist with adoption and application of spatial omics.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Carbon source–driven metabolic and regulatory remodeling defines phenomic states in Lipomyces starkeyi

Lipomyces is a genus of oleaginous yeasts with potential for contributing to reliable biomanufacturing supply chains. However, progress in advanced strain designs and engineering efforts are still constrained by a lack of understanding of the underlying molecular drivers of Lipomyces phenotypes. To address this gap, we collected a suite of multi-omic data to dissect how carbon source availability reshapes the metabolic network, lipid allocation, and regulatory architecture of Lipomyces starkeyi. We observed that glucose promotes biosynthetic and proliferative processes supported by abundant energy and carbon intermediates, xylose enhances redox-balancing mechanisms centered on the pentose phosphate pathway, and glycerol activates respiratory metabolism, ß-oxidation, and the glyoxylate cycle. Lipid species distributions remained consistent in both nitrogen replete and depleted conditions across the carbon sources, indicating robust production mechanisms. Regulatory protein identification and network analysis revealed glycerol-driven respiratory growth favors regulatory programs integrating stress tolerance, redox balance, and lipid-associated metabolism, whereas xylose growth activates compensatory transcriptional responses aimed at maintaining mitochondrial function. Nitrogen limitation modulates the strength of these responses but does not fundamentally alter their direction, reinforcing carbon source as the dominant driver of regulatory architecture. Taken together, this data enhances the understanding of Lipomyces molecular rearrangements and provides a foundation for further development of predictive phenotypic tools in this genus.

Biotechnology↗
DOE OSTI2025

Quantitative decoding of coupled carbon and energy metabolism in Pseudomonas putida for lignin carbon utilization

Soil Pseudomonas species, which thrive on lignin derivatives, are widely explored for biotechnology applications in lignin valorization. However, how the native metabolism coordinates phenolic carbon processing with required cofactor generation remains poorly understood. Here, we achieve quantitative understanding of this metabolic balance through a detailed multi-omics investigation of Pseudomonas putida KT2440 grown on four common phenolic acid substrates: ferulate, p-coumarate, vanillate, and 4-hydroxybenzoate. Relative to succinate, proteomics reveals > 140-fold increase in transport and catabolic proteins for aromatics, but metabolomics identifies bottlenecks in initial catabolism to maintain favorable cellular energy charge, which is compromised in mutants with resolved bottlenecks. Up to 30-fold increase in pyruvate carboxylase and glyoxylate shunt proteins implies a metabolic remodeling confirmed by kinetic 13 C-metabolomics. Quantitative analysis by 13 C-fluxomics demonstrates coupling of this remodeling with cofactor production. Specifically, anaplerotic carbon recycling through pyruvate carboxylase promotes tricarboxylic acid cycle fluxes to generate 50-60% NADPH yield and 60-80% NADH yield, resulting in up to 6-fold greater ATP surplus than with succinate metabolism; the glyoxylate shunt sustains cataplerotic flux through malic enzyme for the remaining NADPH yield. This quantitative blueprint affords cofactor imbalance predictions in proposed engineering of key metabolic nodes in lignin valorization pathways.

09 BIOMASS FUELS↗
DOE OSTI2024

Spatial Proteomics towards cellular Resolution

Introduction: Spatial biology is an emerging interdisciplinary field facilitating biological discoveries through the use of spatial omics technologies. Recent advancements in spatial transcriptomics, spatial genomics (e.g. genetic mutations and epigenetic marks), multiplexed immunofluorescence, and spatial metabolomics/lipidomics have enabled high-resolution spatial profiling of gene expression, genetic variation, protein expression, and metabolites/lipids profiles in tissue. These developments contribute to a deeper understanding of the spatial organization within tissue microenvironments at the molecular level. Areas covered: This report provides an overview of the untargeted, bottom-up mass spectrometry (MS)-based spatial proteomics workflow. It highlights recent progress in tissue dissection, sample processing, bioinformatics, and liquid chromatography (LC)-MS technologies that are advancing spatial proteomics toward cellular resolution. Expert opinion: The field of untargeted MS-based spatial proteomics is rapidly evolving and holds great promise. To fully realize the potential of spatial proteomics, it is critical to advance data analysis and develop automated and intelligent tissue dissection at the cellular or subcellular level, along with high-throughput LC-MS analyses of thousands of samples. In conclusion, achieving these goals will necessitate significant advancements in tissue dissection technologies, LC-MS instrumentation, and computational tools.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

2024 NMDC Ambassador Training Materials [Slides]

The NMDC is a sustainable data discovery platform that promotes open science and shared-ownership across a broad and diverse community of researchers, funders, publishers, societies, and other collaborators. The NMDC aims to enable multi-omic microbiome research to accelerate scientific discovery. The NMDC is a Department of Energy funded program that is a collaboration between 3 National Laboratories: Lawrence Berkeley National Laboratory (LBNL), Los Alamos National Laboratory (LANL), and Pacific Northwest National Laboratory (PNNL).

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2025

Altering translation allows E. coli to overcome G-quadruplex stabilizers

The data included in this Dryad submission was collected in order to understand how the model organism* Escherichia coli* overcomes stabilized G-quadruplexes. This work involved a multi-omics approach to studying how the G-quadruplex stabilizers NMM and Braco-19 impact growth, gene importance, and mRNA/proteomic abundance in G-quadruplex stabilizing conditions.

Bacteria↗
NASA NTRS2016

GeneLab Collaboration

In order to maximize the amount of omics data returned from space flight experiments, the GeneLab project can collaborate with Space Biology funded PIs. Here, we outline the process by which these collaborations take place.

GeneLab↗
NASA NTRSDate not supplied

NASA GeneLab: The NASA Systems Biology Platform for Spaceomics Repository, Analysis and Visualization

At NASA Ames Research Center, the GeneLab Open Science Project is on a mission to gather all large -omics datasets relevant to space biology research. These datasets come from various organisms flown in multiple space habitats such as the International Space Station or the Space Shuttle, in addition to mimicking space-like conditions on ground. Researchers and citizen scientists all around the world have used the data and the analytical tools put together by the GeneLab team to start deciphering new biological impact of microgravity, space ionizing radiation and other space stressors.

GeneLab↗
NASA NTRS2020

The NASA Twins Study: The Effect of One Year in Space on Long-Chain Fatty Acid Desaturases and Elongases

Background: To date, there is no clear understanding of the effect of long-duration spaceflight on the major enzymes that govern the metabolism of omega-6 and omega-3 fatty acids. To address this gap in knowledge, we used data from the NASA Twins Study, which includes a multi-scale omic investigation of the changes that occurred during a year-long (340 days) human spaceflight. Embedded within the NASA Twins data are specific analytes associated with fatty acid metabolism. Objectives: To examine the long-chain fatty acid desaturases and elongases in a single human during one year in space. Method: One male twin was on board the International Space Station (ISS) for one year, while his monozygotic twin served as a genetically matched ground control. Longitudinal assessments included the genome, epigenome, transcriptome, proteome, metabolome, microbiome, and immunome during the mission, as well as six months before and after. The gene-specific fatty acid desaturase and elongase transcriptome data (FADS1, FADS2, ELOVL2 and ELOVL5) were extracted from untargeted RNA-seq measurements derived from white blood cell fractions. Results: Most data from the elongases and desaturases exhibited relatively similar expression profiles (R2>0.6) over time for the CD8, CD19, and LD cell fractions, indicating overall conservation of function within and between the subjects. Both cell-type and temporal specificity was observed in some cases, and some differences were also apparent between the poly-adenylated fraction (polyA) of processed RNAs vs. the ribo-depleted (ribo-) fraction. The flight subject showed a stronger enrichment of the Fatty Acid Metabolic processes pathway across almost all cell types (columns, CD4, CD8, CPT, LD), most especially in the ribodepleted fraction of RNA, but also with the polyA+ fraction of RNA. GSEA enrichment measures across three related Fatty Acid Metabolism pathways showed a differential between the ground and flight subject. Conclusions: There appears to be no persistent alteration of desaturase and elongase gene expression associated with one year in space. However, these data provide evidence that cellular lipid metabolism can be responsive and dynamic to spaceflight, even though it appears cell-type- and context-specific, most notably in terms of the fraction of RNA measured and the collection protocols. These results also provide new evidence of mid-flight spikes in expression of selected genes, which may indicate transient responses to specific insults during spaceflight.

Elongase↗
NASA NTRSDate not supplied

Unlocking the Secrets of Space Biology: From the Twin Study to Groundbreaking Open Science Discoveries

In this interdisciplinary lecture, we will delve into the fascinating world of Space Biology and the realm of Open Science at NASA. Join us as we explore the profound insights gained from the groundbreaking twin study, which was published several years ago and continues to shape our understanding of spaceflight's impact on human health. We will highlight the study's key findings and contextualize them alongside more recent research endeavors, including the remarkable Inspiration 4 mission and several comprehensive meta-analysis publications enabled by the NASA GeneLab Omics database and the Ames Life Science Data Archive for physiological and phenotypic data.

Omics↗
DOE OSTI2025

The microbiologist's guide to metaproteomics

Metaproteomics is an emerging approach for studying microbiomes, offering the ability to characterize proteins that underpin microbial functionality within diverse ecosystems. As the primary catalytic and structural components of microbiomes, proteins provide unique insights into the active processes and ecological roles of microbial communities. By integrating metaproteomics with other omics disciplines, researchers can gain a comprehensive understanding of microbial ecology, interactions, and functional dynamics. This review, developed by the Metaproteomics Initiative (www.metaproteomics.org), serves as a practical guide for both microbiome and proteomics researchers, presenting key principles, state-of-the-art methodologies, and analytical workflows essential to metaproteomics. Topics covered include experimental design, sample preparation, mass spectrometry techniques, data analysis strategies, and statistical approaches.

bioinformatics↗
DOE OSTI2026

Single‐Cell Nanodroplet Processing Proteomics Pipeline for Analysis of Human‐Derived Microglia

Single-cell omics tools provide unique insights into heterogeneous cell populations and their responses to stimuli. For example, single-cell RNA sequencing has identified several transcriptionally distinct populations of microglia, which are resident immune cells of the central nervous system (CNS) that are responsive to CNS injury, infection, and neurodegeneration. To date, single-cell studies of microglia have focused on RNA-sequencing or cytometry by time of flight (CyTOF), which provide indirect readouts of protein abundance or quantification of a limited number of targets. Herein, we present a workflow based on FACS-assisted isolation, cryopreservation, and nanodroplet-based processing for single-cell mass spectrometry proteomics analysis of the postmortem human brain cortex-derived microglia. From a single microglial cell, 1039 proteins could be identified on average. As a proof-of-principle, we applied single-cell proteomics for exploring the heterogeneity of brain microglia at the cellular level. This pilot proteomics data partially recapitulates the prior microglia subtypes. Specifically, we determined that mitochondrial proteins, in particular members of NADH dehydrogenase (Complex I), cytochrome b-c1 (Complex III), cytochrome c oxidase (Complex IV), F1-ATPase (Complex V), and Na+/K+-ATPase complex, drive variation across microglia. This pipeline offers the potential for identifying functionally and analytically relevant protein targets for microglia in Alzheimer's disease and other neurological disorders.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Bleach Rescues Nannochloropsis from an Obligate Parasite and Alters Microbial and Metabolite Signatures of Outdoor Cultures

Chemical agents are commonly used to protect algal crops. Yet, few studies have characterized the effects of these agents on associated microbial communities to understand effects on microbial functions relevant to algal crop production and protection. Here, we used shotgun metagenomic sequencing and untargeted exometabolite profiling to link the application of bleach, a -cidal agent used to protect algae from pests, to changes in community composition, metabolic pathways, and exometabolies - at a whole community level. Bleach protected the algal crop from crashing but altered bacterial diversity. Analysis of metagenome-assembled genomes (MAGs) revealed a classic predator-prey cycle between Oligoflexus and our target alga Nannochloropsis. Olifoflexus genomes from our study were notably similar to a previously identified BALO (Bdellovibrio and like organism), FD111, known to kill Nannochloropsis cultures, providing strong evidence that an FD111-like organism was responsible for the crash. Metabolic pathway composition differed between bleached and unbleached ponds, with abundance of twelve pathways related to stress tolerance, including the superpathway of methylglyoxal degradation, lipid IVA biosynthesis, and ectoine biosynthesis, greater in bleached ponds compared to unbleached ponds. Virulence factors related to adherence, biofilm formation, motility, and pathogenicity increased dramatically in bleached ponds with time, although this increase was not coupled with an increase in pathogens - algal or otherwise - or a decline in algal health. Our study highlights the importance of coupling 16S rRNA gene sequencing with whole genome data and other -omics tools to sketch a larger picture of community structure and function in crop systems. Moreover, our results highlight that continued long-term bleaching may lead to negative effects to crop health or downstream adverse health effects to humans or animals, depending on the algal product (i.e. human supplements or animal feedstocks). Future work on alternative treatment methods that would reduce resistance is necessary in the field.

09 BIOMASS FUELS↗
DOE OSTI2026

Astrocyte Reactivity by Alcohol Dependence in the Central Amygdala

Astrocytes play essential roles in the brain, but prolonged insult can result in the loss or diminishment of homeostatic functions and increased neuroinflammatory response. The central amygdala (CeA) is an important limbic region in reward and stress responsivity as well as in the development of alcohol dependence. Using a multi-omics approach with Aldh1l1-EGFP/Rpl10a mice and the chronic intermittent ethanol – two-bottle choice exposure model, we have characterized the translational response of CeA astrocytes, as well as the proteomic and phosphoproteomic changes in dependent, non-dependent, and naïve mice. We identified astrocyte-specific alterations in neuroimmune functions and antioxidant/oxidative stress pathways in dependent animals while non-dependent EtOH drinking altered cytoskeletal plasticity related pathways. Proteomic analysis showed down-regulation of astrocyte physiological functions in dependent animals while phosphoproteomic analysis identified cytoskeleton remodeling in both dependent and non-dependent animals suggesting the development of a reactive astrocyte phenotype. Astrocyte morphological reconstruction showed increased CeA astrocyte complexity in dependent and non-dependent groups compared to naïve mice. The astrocyte-specific increase in neuroimmune functions, down-regulation of astrocyte homeostatic functions, alteration in protein phosphorylation-mediated cytoskeleton remodeling, and increased astrocyte complexity demonstrate EtOH induced astrocyte activation in the CeA and suggest the presence of both adaptive and maladaptive reactive astrocytes. These findings highlight the roles CeA astrocytes play in the progression of alcohol intake to dependence and are the first step in the identification of novel astrocyte-specific therapeutic approaches for alcohol use disorder through the potentiation of adaptive changes and inhibition of maladaptive changes in astrocytes.

Hashimoto, Joel↗