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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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At least 91 records · Page 5
All sourcesNASA NTRSDOE OSTI
DOE OSTI2026

Constitutive and inducible oleoresin defenses share genetic architectures and mechanisms in Pinus taeda

The oleoresin defense system of loblolly pine (Pinus taeda) protects trees from insects and pathogens and is an important source of renewable biofuels and chemicals, but the genetic basis of oleoresin production is poorly understood. We characterized the genetic architecture of oleoresin flow, resin canal number, stem wood terpene content, and monoterpene composition in two clonal populations of P. taeda. We used quantitative genetic analyses, genome-wide association studies (GWASs), multiplex network learning, and gene expression profiling to elucidate shared gene networks underlying defense traits and to identify high-quality candidates for breeding and engineering loblolly pine. Genetic analyses revealed polygenic inheritance and trait-to-trait correlations provide strong evidence for shared genes regulating constitutive and induced oleoresin flow. We identified 236 single nucleotide polymorphisms associated with oleoresin flow, resin canal number, and terpene composition and highlight candidate genes likely involved in terpene biosynthesis, cambial meristem reprogramming, and pathogen perception and immune signaling. Fourteen GWAS candidates were methyl jasmonate-responsive in tissues where resin canals initiate and terpene production occurs. Integrating quantitative genetics, GWAS, gene expression, and multiplex network analyses enabled the prioritization of high-quality candidate genes. This work advances the development of more resilient loblolly pine optimized for ecological performance, renewable chemical, and biofuel production.

genome-wide association study↗
DOE OSTI2024

AtDGCR14L contributes to salt-stress tolerance via regulating pre-mRNA splicing in Arabidopsis

In plants, the pre-mRNA alternative splicing has been demonstrated to be a crucial tier that regulates gene expression in response to salt stress. However, the underlying mechanisms remain elusive. Here, in this study, we studied the roles of DIGEORGE-SYNDROME CRITICAL REGION 14-like (AtDGCR14L) in regulating pre-mRNA splicing and salt stress tolerance. We discovered that Arabidopsis AtDGCR14L is required for maintaining plant salt stress tolerance and the constitutively spliced and active isoforms of important stress- and/or abscisic acid (ABA)-responsive genes. We also identified the interaction between AtDGCR14L and splicing factor U1-70k, which needs a highly conserved three amino acid (TWG) motif in DGCR14. Different from wild-type AtDGCR14L, the overexpression of TWG-substituted AtDGCR14L mutant did not change salt stress tolerance or pre-mRNA splicing of stress/ABA-responsive genes. Additionally, SWITCH3A (SWI3A) is a core subunit of the SWI/SUCROSE NONFERMENTING (SWI/SNF) chromatin-remodeling complexes. We found that SWI3A, whose splicing depends on AtDGCR14L, actively enhances salt stress tolerance. These results revealed that AtDGCR14L may play an essential role in crosstalk between plant salt-stress response and pre-mRNA splicing mechanisms. We also unveiled the potential role of SWI3A in controlling salt stress tolerance. The TWG motif in the intrinsically disordered region of AtDGCR14L is highly conserved and crucial for DGCR14 functions.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

NuclPred v1

This tool takes a genome assembly as input and predicts per-site nucleosome occupancy as output. Trained on physical maps of nucleosome binding preferences across the fungal kingdom, NuclPred can be applied broadly across fungi (and other eukaryotes). This breadth, combined with its accuracy, means it could have both basic and applied biological implications, for example in understanding eukaryotic gene regulation and genetic engineering. Almost universally across eukaryotes, nucleosomes - each wrapping ~150 base pairs of DNA - serve to package DNA inside the nucleus, with major consequences on DNA access, gene activity and DNA integration. NuclPred was generated using a supervised deep learning approach combining convolutional and recurrent neural networks to take DNA features (nucleotides, GC content and structural information) as input, then use that information to predict the physical attractiveness DNA sequences might have for forming nucleosomes. With this information at hand, researchers can design more efficient CRISPR constructs, explore the interplay between DNA signatures and other regulators impact nucleosome locations, predict expression patterns, etc. This tool will be published as part of a manuscript currently under revision at iScience (draft attached).

Mondo, Stephen↗
DOE OSTI2025

Symmetric adenine methylation is an essential DNA modification in the early-diverging fungus Rhizopus microsporus

The discovery of N6-methyladenine (6mA) in eukaryotic genomes, typically found in prokaryotic DNA, has revolutionized epigenetics. Here, we show that symmetric 6mA is essential in the early diverging fungus Rhizopus microsporus, as the absence of the MT-A70 complex (MTA1c) responsible for this modification results in a lethal phenotype. 6mA is present in 70% of the genes, correlating with the presence of H3K4me3 and H2A.Z in open euchromatic regions. This modification is found predominantly in nucleosome linker regions, influencing the nucleosome positioning around the transcription start sites of highly expressed genes. Controlled downregulation of MTA1c reduces symmetric 6mA sites affecting nucleosome positioning and histone modifications, leading to altered gene expression, which is likely the cause of the severe phenotypic changes observed. Our study highlights the indispensable role of the DNA 6mA in a multicellular organism and delineates the mechanisms through which this epigenetic mark regulates gene expression in a eukaryotic genome.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1999

Gravitational Effects on Signal Transduction

An understanding of the mechanisms by which individual cells perceive gravity and how these cells transduce and respond to gravitational stimuli is critical for the development of long-term manned space flight experiments. We now propose to use a well-characterized model erythroid cell system and to investigate gravitational perturbations of its erythropoietin (Epo) signaling pathway and gene regulation. Cells will be grown at 1-G and in simulated microgravity in the NASA Rotating Wall Vessel bioreactor (RWV). Cell growth and differentiation, the Epo-receptor, the protein kinase C pathway to the c-myc gene, and the protein phosphatase pathway to the c-myb gene will be studied and evaluated as reporters of gravitational stimuli. The results of these experiments will have impact on the problems of 1) gravitational sensing by individual cells, and 2) the anemia of space flight. This ground-based study also will serve as a Space Station Development Study in gravitational effects on intracellular signal transduction.

Sytkowski, Arthur J.↗
DOE OSTI2026

Three pairs of fungal Trametes strains isolated from distinct geographic origins show conserved genomic features and adaptive response to plant biomass

The genomes of white-rot fungi hold extended repertoires of enzymes active on virtually all the chemical bonds that intertwine lignocellulose polymers, and several Trametes species have been identified as powerful tools for biorefinery or bioremediation. However, only few studies have addressed the intra-species polymorphism one would expect from fungal strains collected in contrasted environments. We compared the genome sequence of pairs of strains collected in different geographic areas, for each of three fungal species. Using an updated list of the predicted functions for fungal ligno- and cellulolytic enzymes (CAZymes), we observed a high conservation of the gene repertoires among the six strains. We compared the adaptative response of the fungi grown on crystalline cellulose, wheat straw, aspen or pine sawdust by transcriptomics and secretomics. The gene regulation profiles were determined by the species and the substrates, rather than the strain. The secretomes did not show marked differences in the sets of secreted CAZymes after 3 day-growth on the substrates. We identified five transcription factor genes and two sesquiterpenoid synthesis genes induced during growth on lignocellulose. Wider studies using larger sets of strains will be necessary to evaluate the genericity of our findings, and to assess the phenotype diversity one could expect from geographic diversity as compared to taxonomic diversity in Trametes fungi.

Drula, E. [French National Research Institute for ↗
NASA NTRS1999

Is skeletal muscle ready for long-term spaceflight and return to gravity?

It is now clear that prevention of muscle debilitation during spaceflight will require a broader approach than simple exercise aimed at strengthening of the muscle fibers. The levels of several hormones and receptors are altered by unloading and must be returned to homeostasis. Pharmacotherapy and gene transfer strategies to raise the relative level of structural proteins may minimize the problems faced by astronauts in readapting to Earth-gravity. Up to now, we have only minimally exploited microgravity for advancing our understanding of muscle biology. A research laboratory in the space station with a centrifuge facility (gravity control) is essential for conducting basic research in this field. Microgravity has proven an excellent tool for noninvasively perturbing the synthesis of muscle proteins in the search for molecular signals and gene regulatory factors influencing differentiation, growth, maintenance and atrophy of muscle. Understanding the relation between blood flow and interstitial edema and between workload and subsequent structural failure are but two important problems that require serious attention. The roles of hormones and growth factors in regulating gene expression and their microgravity-induced altered production are other urgent issues to pursue. These types of studies will yield information that advances basic knowledge of muscle biology and offers insights into countermeasure design. This knowledge is likely to assist rehabilitation of diseased or injured muscles in humans on Earth, especially individuals in the more vulnerable aging population and persons participating in strenuous sports. Will the skeletal muscle system be prepared for the increased exposure to microgravity and the return to gravity loading without injury when space station is operational? The answer depends in large part on continued access to space and funding of ground-based models and flight experiments. The previous two decades of spaceflight research have described the effects of microgravity on multiple systems. The next generation of experiments promises to be even more exciting as we are challenged to define the cellular and molecular mechanisms of microgravity-induced changes.

manned↗
NASA NTRS2016

Epigenetics Research on the International Space Station

The International Space Station (ISS) is a state-of-the orbiting laboratory focused on advancing science and technology research. Experiments being conducted on the ISS include investigations in the emerging field of Epigenetics. Epigenetics refers to stably heritable changes in gene expression or cellular phenotype (the transcriptional potential of a cell) resulting from changes in a chromosome without alterations to the underlying DNA nucleotide sequence (the genetic code), which are caused by external or environmental factors, such as spaceflight microgravity. Molecular mechanisms associated with epigenetic alterations regulating gene expression patterns include covalent chemical modifications of DNA (e.g., methylation) or histone proteins (e.g., acetylation, phorphorylation, or ubiquitination). For example, Epigenetics ("Epigenetics in Spaceflown C. elegans") is a recent JAXA investigation examining whether adaptations to microgravity transmit from one cell generation to another without changing the basic DNA of the organism. Mouse Epigenetics ("Transcriptome Analysis and Germ-Cell Development Analysis of Mice in Space") investigates molecular alterations in organ-specific gene expression patterns and epigenetic modifications, and analyzes murine germ cell development during long term spaceflight, as well as assessing changes in offspring DNA. NASA's first foray into human Omics research, the Twins Study ("Differential effects of homozygous twin astronauts associated with differences in exposure to spaceflight factors"), includes investigations evaluating differential epigenetic effects via comprehensive whole genome analysis, the landscape of DNA and RNA methylation, and biomolecular changes by means of longitudinal integrated multi-omics research. And the inaugural Genes in Space student challenge experiment (Genes in Space-1) is aimed at understanding how epigenetics plays a role in immune system dysregulation by assaying DNA methylation in immune cells directly in space using miniPCR technology. In addition, NASA's geneLAB campaign covers the epigenome as part of the "expressome", by employing an innovative open source science platform for multi-investigator high throughput utilization of the ISS. Earth benefits of Epigenetics research onboard the ISS range from contributions to the fundamental understanding of epigenetic phenomena with applications in countermeasure development for biomedical conditions, to the generation of integrated strategies for personalized medicine based on unique physiological responses.

Love, John↗
NASA NTRS2000

T Lymphocyte Activation Threshold is Increased in Reduced Gravity

There have been substantial advances in molecular and cellular biology that have provided new insight into the biochemical and genetic basis of lymphocyte recognition, activation and expression of distinct functional phenotypes. It has now become evident that for both T and B cells, stimuli delivered through their receptors can result in either clonal expansion or apoptosis. In the case of T cells, clonal expansion of helper cells is accompanied by differentiation into two major functional subsets which regulate the immune response. The pathways between the membrane and the nucleus and their molecular components are an area of very active investigation. This meeting will draw together scientists working on diverse aspects of this problem, including receptor ligand interactions, intracellular pathways that transmit receptor mediated signals and the effect of such signal transduction pathways on gene regulation. The aim of this meeting is to integrate the information from these various experimental approaches into a new synthesis and molecular explanation of T cell activation, differentiation and death.

Adams, Charley L.↗
DOE OSTI2026

CRAGE-RB-PI-seq reveals transcriptional dynamics of plant-associated bacteria during root colonization

Plant roots release a wide array of metabolites into the rhizosphere, shaping microbial communities and their functions. While metagenomics has expanded our understanding of these communities, little is known about the physiology of their members in host environments. Transcriptome analysis via RNA sequencing is a common approach to learning more, but its use has been challenging because of low bacterial biomass and interference from plant RNA. To overcome this, we developed a randomly-barcoded promoter-library insertion sequencing (RB-PI-seq) combined with chassis-independent recombinase-assisted genome engineering (CRAGE). Using Pseudomonas simiae WCS417 as a model rhizobacterium, this method enabled targeted amplification of barcoded transcripts, bypassing plant RNA interference and allowing measurement of thousands of promoter activities during Arabidopsis root colonization. Our analysis revealed temporally resolved transcriptional regulation, including those associated with cell growth, chemotaxis, plant immune suppression, biofilm formation, and stress responses, reflecting the coordinated physiological adaptation to the root environment. Additionally, we discovered that transcriptional activation of xanthine dehydrogenase and a lysozyme inhibitor is crucial for evading plant immune systems. This framework is scalable to other bacterial species and provides new opportunities for understanding rhizobacterial gene regulation in native environments.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

An expanded registry of candidate cis -regulatory elements

Mammalian genomes contain millions of regulatory elements that control the complex patterns of gene expression. Previously, the ENCODE consortium mapped biochemical signals across hundreds of cell types and tissues and integrated these data to develop a registry containing 0.9 million human and 300,000 mouse candidate cis-regulatory elements (cCREs) annotated with potential functions. Here we have expanded the registry to include 2.37 million human and 967,000 mouse cCREs, leveraging new ENCODE datasets and enhanced computational methods. This expanded registry covers hundreds of unique cell and tissue types, providing a comprehensive understanding of gene regulation. Functional characterization data from assays such as STARR-seq, massively parallel reporter assay, CRISPR perturbation and transgenic mouse assays have profiled more than 90% of human cCREs, revealing complex regulatory functions. We identified thousands of novel silencer cCREs and demonstrated their dual enhancer and silencer roles in different cellular contexts. Integrating the registry with other ENCODE annotations facilitates genetic variation interpretation and trait-associated gene identification, exemplified by the identification of KLF1 as a novel causal gene for red blood cell traits. This expanded registry is a valuable resource for studying the regulatory genome and its impact on health and disease.

Moore, Jill E. [Univ. of Massachusetts, Worchester↗
DOE OSTI2024

Highly multiplexed design of an allosteric transcription factor to sense new ligands

Allosteric transcription factors (aTF) regulate gene expression through conformational changes induced by small molecule binding. Although widely used as biosensors, aTFs have proven challenging to design for detecting new molecules because mutation of ligand-binding residues often disrupts allostery. Here, we develop Sensor-seq, a high-throughput platform to design and identify aTF biosensors that bind to non-native ligands. We screen a library of 17,737 variants of the aTF TtgR, a regulator of a multidrug exporter, against six non-native ligands of diverse chemical structures – four derivatives of the cancer therapeutic tamoxifen, the antimalarial drug quinine, and the opiate analog naltrexone – as well as two native flavonoid ligands, naringenin and phloretin. Sensor-seq identifies biosensors for each of these ligands with high dynamic range and diverse specificity profiles. The structure of a naltrexone-bound design shows shape-complementary methionine-aromatic interactions driving ligand specificity. To demonstrate practical utility, we develop cell-free detection systems for naltrexone and quinine. Sensor-seq enables rapid and scalable design of new biosensors, overcoming constraints of natural biosensors.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2018

Genetic Regulation of Bone and Cells by Electromagnetic Stimulation Fields and Uses Thereof

The present invention provides methods to modify the genetic regulation of mammalian tissue, bone, cells or any combination thereof by preferential activation, up-regulation and/or down-regulation. The method comprises steps of tuning the predetermined profiles of one or more time-varying stimulation fields by manipulating the B-Field magnitude, rising slew rate, rise time, falling slew rate, fall time, frequency, wavelength, and duty cycle, and exposing mammalian cells or tissues to one or more tuned time-varying stimulation fields with predetermined profiles. Examples of mammalian cells or tissues are chondrocytes, osteoblasts, osteocytes, osteoclasts, nucleus pulposus, associated tissue, or any combination. The resulted modification on gene regulation of these cells, tissues or bones may promote the retention, repair of and reduction of compromised mammalian cartilage, bone, and associated tissue.

Goodwin, Thomas J.↗
DOE OSTI2025

PERCEPTIVE: an R shiny $\underline{p}$ipelin$\underline{e}$ for the p$\underline{r}$edi$\underline{c}$tion of $\underline{ep}$igenetic modula$\underline{t}$ors $\underline{i}$n no$\underline{v}$el sp$\underline{e}$cies

Epigenetic processes are central to regulating gene expression, genome stability, and metabolic function across the tree of life; yet, their roles remain underexplored in microalgae, especially as new species continue to be identified and characterized. This is likely due to the cumbersome nature and species-dependent attributes of epigenetic wet-lab methodologies, which preclude the rapid identification of epigenetic modifications and modulators. However, there is high conservation of epigenetic processes from budding yeast to humans; in many cases, one may infer how behavior and function are epigenetically regulated in novel species by identifying epigenetic modulators, or the proteins responsible for conferring epigenetic modifications. Here, to this end, we have developed a graphical software package, titled PERCEPTIVE (pipeline for the prediction of epigenetic modulators in novel species). This platform solely uses the genomic sequence of an algal species, and preexisting information from other model organisms, to predict the epigenetic modulators and associated modifications in algae. Predictions are presented to the user in a graphical interface, which provides literature-based interpretation of results, enabling users to quickly understand potential epigenetic processes in their algal species of interest and plan follow-up experiments. To test PERCEPTIVE, we predicted epigenetic modulators in several feedstock candidate algae species. To validate these predictions, wet-lab studies were performed, including mass spectrometry; these results underscore the high accuracy of PERCEPTIVE predictions. Overall, PERCEPTIVE represents a powerful in silico tool for the research and manipulation of algal species, which does not require a priori knowledge of epigenetics and is accessible to a broad set of investigators.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Learning genetic perturbation effects with variational causal inference

Advances in sequencing technologies have enhanced the understanding of gene regulation in cells. In particular, Perturb-seq has enabled high-resolution profiling of the transcriptomic response to genetic perturbations at the single-cell level. This understanding has implications in functional genomics and potentially for identifying therapeutic targets. Various computational models have been developed to predict perturbational effects. While deep learning models excel at interpolating observed perturbational data, they tend to overfit in the lack of enough data and may not generalize well to unseen perturbations. In contrast, mechanistic models, such as linear causal models based on gene regulatory networks, hold greater potential for extrapolation, as they encapsulate regulatory information that can predict responses to unseen perturbations. However, their application has been limited to small studies due to overly simplistic assumptions, making them less effective in handling noisy, large-scale single-cell data. We propose a hybrid approach that combines a mechanistic causal model with variational deep learning, termed Single Cell Causal Variational Autoencoder (SCCVAE). The mechanistic model employs a learned regulatory network to represent perturbational changes as shift interventions that propagate through the learned network. SCCVAE integrates this mechanistic causal model into a variational autoencoder, generating rich, comprehensive transcriptomic responses. Our results indicate that SCCVAE exhibits superior performance over current state-of-the-art baselines for extrapolating to predict unseen perturbational responses. Additionally, for the observed perturbations, the latent space learned by SCCVAE allows for the identification of functional perturbation modules and simulation of single-gene knockdown experiments of varying penetrance, presenting a robust tool for interpreting and interpolating perturbational responses at the single-cell level.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Multiplexed profiling of transcriptional regulators in plant cells

Transcriptional regulators play key roles in plant growth, development and environmental responses; however, understanding how their regulatory activity is encoded at the protein level has been hindered by a lack of multiplexed large-scale methods to characterize protein libraries in planta. Here we present enrichment of nuclear trans-elements reporter assay in plants with sequencing (ENTRAP-seq), a high-throughput method that introduces protein-coding libraries into plant cells to drive a nuclear magnetic sorting-based reporter, enabling multiplexed measurement of regulatory activity from thousands of protein variants. Using ENTRAP-seq and machine learning, we screen 1,495 plant viruses and identify hundreds of putative transcriptional regulatory domains found in structural proteins and enzymes not associated with gene regulation. In addition, we combine ENTRAP-seq with machine-guided design to engineer the activity of a plant transcription factor in a semirational fashion. Our findings demonstrate how scalable protein function assays deployed in planta will enable the characterization of natural and synthetic coding diversity in plants.

Alamos, Simon↗
NASA NTRS1999

Delayed expression of hpS2 and prolonged expression of CIP1/WAF1/SDI1 in human tumour cells irradiated with X-rays, fission neutrons or 1 GeV/nucleon Fe ions

PURPOSE: Differences in gene expression underlie the phenotypic differences between irradiated and unirradiated cells. The goal was to identify late-transcribed genes following irradiations differing in quality, and to determine the RBE of 1 GeV/n Fe ions. MATERIALS AND METHODS: Clonogenic assay was used to determine the RBE of Fe ions. Differential hybridization to cDNA target clones was used to detect differences in expression of corresponding genes in mRNA samples isolated from MCF7 cells irradiated with iso-survival doses of Fe ions (0 or 2.5 Gy) or fission neutrons (0 or 1.2 Gy) 7 days earlier. Northern analysis was used to confirm differential expression of cDNA-specific mRNA and to examine expression kinetics up to 2 weeks after irradiation. RESULTS: Fe ion RBE values were between 2.2 and 2.6 in the lines examined. Two of 17 differentially expressed cDNA clones were characterized. hpS2 mRNA was elevated from 1 to 14 days after irradiation, whereas CIP1/WAF1/SDI1 remained elevated from 3 h to 14 days after irradiation. Induction of hpS2 mRNA by irradiation was independent of p53, whereas induction of CIP1/WAF1/SDI1 was observed only in wild-type p53 lines. CONCLUSIONS: A set of coordinately regulated genes, some of which are independent of p53, is associated with change in gene expression during the first 2 weeks post-irradiation.

NASA Discipline Radiation Health↗
DOE OSTI2025

Revealing systematic changes in the transcriptome during the transition from exponential growth to stationary phase

ABSTRACT The composition of bacterial transcriptomes is determined by the transcriptional regulatory network (TRN). The TRN regulates the transition from one physiological state to another. Here, we use independent component analysis to monitor the composition of the transcriptome during the transition from the exponential growth phase to the stationary phase. With Escherichia coli K-12 MG1655 as a model strain, we trigger the transition using carbon, nitrogen, and sulfur starvation. We find that (i) the transition to the stationary phase accompanies common transcriptome changes, including increased stringent responses and reduced production of cellular building blocks and energy regardless of the limiting element; (ii) condition-specific changes are strongly associated with transcriptional regulators ( e.g. , Crp, NtrC, CysB, Cbl) responsible for metabolizing the limiting element; and (iii) the shortage of each limiting element differentially affects the production of amino acids and extracellular polymers. This study demonstrates how the combination of genome-scale datasets and new data analytics reveals the fundamental characteristics of a key transition in the life cycle of bacteria. IMPORTANCE Nutrient limitations are critical environmental perturbations in bacterial physiology. Despite its importance, a detailed understanding of how bacterial transcriptomes are adjusted has been limited. By utilizing independent component analysis (ICA) to decompose transcriptome data, this study reveals key regulatory events that enable bacteria to adapt to nutrient limitations. The findings not only highlight common responses, such as the stringent response, but also condition-specific regulatory shifts associated with carbon, nitrogen, and sulfur starvation. The insights gained from this work advance our knowledge of bacterial physiology, gene regulation, and metabolic adaptation.

Lim, Hyun Gyu (ORCID:0000000204692388)↗