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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 19 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS2001

Evolution, language and analogy in functional genomics

Almost a century ago, Wittgenstein pointed out that theory in science is intricately connected to language. This connection is not a frequent topic in the genomics literature. But a case can be made that functional genomics is today hindered by the paradoxes that Wittgenstein identified. If this is true, until these paradoxes are recognized and addressed, functional genomics will continue to be limited in its ability to extrapolate information from genomic sequences.

Evolution, Molecular↗
NASA NTRS2003

Quantitative analysis of bristle number in Drosophila mutants identifies genes involved in neural development

BACKGROUND: The identification of the function of all genes that contribute to specific biological processes and complex traits is one of the major challenges in the postgenomic era. One approach is to employ forward genetic screens in genetically tractable model organisms. In Drosophila melanogaster, P element-mediated insertional mutagenesis is a versatile tool for the dissection of molecular pathways, and there is an ongoing effort to tag every gene with a P element insertion. However, the vast majority of P element insertion lines are viable and fertile as homozygotes and do not exhibit obvious phenotypic defects, perhaps because of the tendency for P elements to insert 5' of transcription units. Quantitative genetic analysis of subtle effects of P element mutations that have been induced in an isogenic background may be a highly efficient method for functional genome annotation. RESULTS: Here, we have tested the efficacy of this strategy by assessing the extent to which screening for quantitative effects of P elements on sensory bristle number can identify genes affecting neural development. We find that such quantitative screens uncover an unusually large number of genes that are known to function in neural development, as well as genes with yet uncharacterized effects on neural development, and novel loci. CONCLUSIONS: Our findings establish the use of quantitative trait analysis for functional genome annotation through forward genetics. Similar analyses of quantitative effects of P element insertions will facilitate our understanding of the genes affecting many other complex traits in Drosophila.

Non-NASA Center↗
NASA NTRS2003

Calcium/calmodulin-mediated signal network in plants

Various extracellular stimuli elicit specific calcium signatures that can be recognized by different calcium sensors. Calmodulin, the predominant calcium receptor, is one of the best-characterized calcium sensors in eukaryotes. In recent years, completion of the Arabidopsis genome project and advances in functional genomics have helped to identify and characterize numerous calmodulin-binding proteins in plants. There are some similarities in Ca(2+)/calmodulin-mediated signaling in plants and animals. However, plants possess multiple calmodulin genes and many calmodulin target proteins, including unique protein kinases and transcription factors. Some of these proteins are likely to act as "hubs" during calcium signal transduction. Hence, a better understanding of the function of these calmodulin target proteins should help in deciphering the Ca(2+)/calmodulin-mediated signal network and its role in plant growth, development and response to environmental stimuli.

NASA Discipline Plant Biology↗
NASA NTRS2004

Biodosimetry as a New Paradigm for Determination of Radiation Risks and Risk-Mitigation in Astronauts Exposed to Space Radiation

Predicting risk of cancer in astronauts exposed to space radiation is challenging partly because uncertainties of absorption of dose and the processing of dose-related damage at the cellular level degrade the confidence of predicting the expression of cancer. Cellular biodosimeters that simultaneously report: 1) the quantity of absorbed dose after exposure to ionizing radiation, 2) the quality of radiation delivering that dose, and 3) the macromolecular profiles related to malignant transformation in cells absorbing that dose would therefore be useful. An approach to such a multiparametric biodosimeter will be reported, This is the demonstration of two dose-responsive field-effects of enhanced protein-expression. In one case, expression of keratin 18 (K18) in cultures of human mammary epithelial cells (HMEC) irradiated with cesium-137 gamma-rays is enhanced following exposure of log phase cells to relatively low doses of 30 to 90 cGy. K18 has been reported by a marker for tumor staging and for apoptosis. In the second case, expression of connexin 43 (Cx43) is increased in irradiated stationary phase cultures of HMEC, indicating enhanced formation of gap junctions. Gap junctions have been reported to be involved in bystander effects following irradiation. It is a biodosimeter for assessing radiogenic damage. It is suggested further that such biomolecular dosimetry may introduce a new paradigm for assessing cancer risk and risk-mitigation in individuals, a requirement for managing radiation health in astronauts during extended missions in space. This new paradigm is built upon the statistical power provided by the use of functional genomics and proteomics represented in combined gene- and protein-expression assays.

Richmond, Robert↗
NASA NTRS2015

Interphase Chromosome Conformation and Chromatin-Chromatin Interactions in Human Epithelial Cells Cultured Under Different Gravity Conditions

Microgravity has been shown to alter global gene expression patterns and protein levels both in cultured cells and animal models. It has been suggested that the packaging of chromatin fibers in the interphase nucleus is closely related to genome function, and the changes in transcriptional activity are tightly correlated with changes in chromatin folding. This study explores the changes of chromatin conformation and chromatin-chromatin interactions in the simulated microgravity environment, and investigates their correlation to the expression of genes located at different regions of the chromosome. To investigate the folding of chromatin in interphase under various culture conditions, human epithelial cells, fibroblasts, and lymphocytes were fixed in the G1 phase. Interphase chromosomes were hybridized with a multicolor banding in situ hybridization (mBAND) probe for chromosome 3 which distinguishes six regions of the chromosome as separate colors. After images were captured with a laser scanning confocal microscope, the 3-dimensional structure of interphase chromosome 3 was reconstructed at multi-mega base pair scale. In order to determine the effects of microgravity on chromosome conformation and orientation, measures such as distance between homologous pairs, relative orientation of chromosome arms about a shared midpoint, and orientation of arms within individual chromosomes were all considered as potentially impacted by simulated microgravity conditions. The studies revealed non-random folding of chromatin in interphase, and suggested an association of interphase chromatin folding with radiation-induced chromosome aberration hotspots. Interestingly, the distributions of genes with expression changes over chromosome 3 in cells cultured under microgravity environment are apparently clustered on specific loci and chromosomes. This data provides important insights into how mammalian cells respond to microgravity at molecular level.

International Space Station↗
NASA NTRS2019

Nasa GeneLab Computomics Reveal Horizontal Gene Transfer on International Space Station Environmental Metagenomes

Prokaryotic lifeforms can be observed to demonstrate many keen adaptive advantages, perhaps facilitated by a nature simplistic relative to divergent domains of life. In particular, decompartmentalized gene expression facilitates adaptation by allowing free exchange of genetic material, albeit at the cost of increased susceptibility to genetic damage. Thus, these lifeforms must compensate by embracing diverse investment strategies in an attempt to “brute force” the evolvability equation through precipitous genesis, lean metabolic efficiency, and sheer population. This prokaryotic archetype also enables symbiotic relationships with secondary mobile genetic elements known as plasmids, which have been shown to drive evolution on rapid temporal scales through processes such as conjugation and transformation. This study attempts to decipher whether these mechanisms of horizontal gene transfer (HGT) are major factors in determining prokaryote fitness within a unique isolated environment, the International Space Station (ISS). The ISS Microbial Tracking (MT) project has generated a wealth of data concerning the successive reigns of microbial genera that appear to thrive amidst harsh conditions for life. Despite relatively higher doses of ionizing radiation as compared to Earth, complications associated with microgravity, and the anti-microbial mélange deployed, microbial life still persists in this environment. The NASA GeneLab serves as a data repository and analysis platform to enable researchers to access space flight factor related data. With the use of GeneLab’s modern computational suites (computomics), phylogenetic and functional genomic investigations of HGT events were conducted on the data generated from the MT-1 project. The putative data concerning the plasmid population (plasmidome) of the ISS was algorithmically derived and compared to those of habitats with similar environmental dynamics- such as living quarters and hospitals- to investigate whether these HGT elements may play crucial role(s) in shaping the microbiome of this closed habitat that serves as the only inhabited structure in space.

Bense, Nicholas↗
NASA NTRS2003

Simple Math is Enough: Two Examples of Inferring Functional Associations from Genomic Data

Non-random features in the genomic data are usually biologically meaningful. The key is to choose the feature well. Having a p-value based score prioritizes the findings. If two proteins share a unusually large number of common interaction partners, they tend to be involved in the same biological process. We used this finding to predict the functions of 81 un-annotated proteins in yeast.

Liang, Shoudan↗
NASA NTRS2017

Behavioral, Brain Imaging and Genomic Measures to Predict Functional Outcomes Post-Bed Rest and Space Flight

Astronauts experience sensorimotor disturbances during their initial exposure to microgravity and during the re-adaptation phase following a return to an Earth-gravitational environment. These alterations may disrupt crewmembers' ability to perform mission critical functional tasks requiring ambulation, manual control and gaze stability. Interestingly, astronauts who return from spaceflight show substantial differences in their abilities to readapt to a gravitational environment. The ability to predict the manner and degree to which individual astronauts are affected will improve the effectiveness of countermeasure training programs designed to enhance sensorimotor adaptability. For such an approach to succeed, we must develop predictive measures of sensorimotor adaptability that will allow us to foresee, before actual spaceflight, which crewmembers are likely to experience greater challenges to their adaptive capacities. The goals of this project are to identify and characterize this set of predictive measures. Our approach includes: 1) behavioral tests to assess sensory bias and adaptability quantified using both strategic and plastic-adaptive responses; 2) imaging to determine individual brain morphological and functional features, using structural magnetic resonance imaging (MRI), diffusion tensor imaging, resting state functional connectivity MRI, and sensorimotor adaptation task-related functional brain activation; and 3) assessment of genetic polymorphisms in the catechol-O-methyl transferase, dopamine receptor D2, and brain-derived neurotrophic factor genes and genetic polymorphisms of alpha2-adrenergic receptors that play a role in the neural pathways underlying sensorimotor adaptation. We anticipate that these predictive measures will be significantly correlated with individual differences in sensorimotor adaptability after long-duration spaceflight and exposure to an analog bed rest environment. We will be conducting a retrospective study, leveraging data already collected from relevant ongoing or completed bed rest and spaceflight studies. This data will be combined with predictor metrics that will be collected prospectively (as described for behavioral, brain imaging and genomic measures) from these returning subjects to build models for predicting post spaceflight and bed rest adaptive capability. In this presentation we will discuss the optimized set of tests for predictive metrics to be used for evaluating post mission adaptive capability as manifested in their outcome measures. Comparisons of model performance will allow us to better design and implement sensorimotor adaptability training countermeasures against decrements in post-mission adaptive capability that are customized for each crewmember's sensory biases, adaptive ability, brain structure, brain function, and genetic predispositions. The ability to customize adaptability training will allow more efficient use of crew time during training and will optimize training prescriptions for astronauts to mitigate the deleterious effects of spaceflight.

Mulavara, A. P.↗
NASA NTRS2016

Behavioral, Brain Imaging and Genomic Measures to Predict Functional Outcomes Post - Bed Rest and Spaceflight

Astronauts experience sensorimotor disturbances during their initial exposure to microgravity and during the re-adaptation phase following a return to an Earth-gravitational environment. These alterations may disrupt crewmembers' ability to perform mission critical functional tasks requiring ambulation, manual control and gaze stability. Interestingly, astronauts who return from spaceflight show substantial differences in their abilities to readapt to a gravitational environment. The ability to predict the manner and degree to which individual astronauts would be affected would improve the effectiveness of countermeasure training programs designed to enhance sensorimotor adaptability. For such an approach to succeed, we must develop predictive measures of sensorimotor adaptability that will allow us to foresee, before actual spaceflight, which crewmembers are likely to experience the greatest challenges to their adaptive capacities. The goals of this project are to identify and characterize this set of predictive measures. Our approach includes: 1) behavioral tests to assess sensory bias and adaptability quantified using both strategic and plastic-adaptive responses; 2) imaging to determine individual brain morphological and functional features, using structural magnetic resonance imaging (MRI), diffusion tensor imaging, resting state functional connectivity MRI, and sensorimotor adaptation task-related functional brain activation; and 3) assessment of genotypic markers of genetic polymorphisms in the catechol-O-methyl transferase, dopamine receptor D2, and brain-derived neurotrophic factor genes and genetic polymorphisms of alpha2-adrenergic receptors that play a role in the neural pathways underlying sensorimotor adaptation. We anticipate that these predictive measures will be significantly correlated with individual differences in sensorimotor adaptability after long-duration spaceflight and exposure to an analog bed rest environment. We will be conducting a retrospective study, leveraging data already collected from relevant ongoing or completed bed rest and spaceflight studies. These data will be combined with predictor metrics that will be collected prospectively (as described for behavioral, brain imaging and genomic measures) from these returning subjects to build models for predicting post-mission (bed rest - non-astronauts or space flight - astronauts) adaptive capability as manifested in their outcome measures. To date we have completed a study on 15 normal subjects with all of the above measures. In this presentation we will discuss the optimized set of tests for predictive metrics to be used for evaluating post mission adaptive capability as manifested in their outcome measures. Comparisons of model performance will allow us to better design and implement sensorimotor adaptability training countermeasures against decrements in post-mission adaptive capability that are customized for each crewmember's sensory biases, adaptive capacity, brain structure and functional capacities, and genetic predispositions. The ability to customize adaptability training will allow more efficient use of crew time during training and will optimize training prescriptions for astronauts to ensure expected outcomes.

Mulavara, A. P.↗
NASA NTRSDate not supplied

Genetic Determinants of Microbial Survival in Space

Space flight agencies envision a future for humankind beyond Earth, including missions back to the Moon and to Mars in the coming decades. Sending humans into space inevitably includes their microbiomes as well, leading to trillions of bacteria being shed in their living areas. These bacteria shape the lives of their hosts as well as their environment; thus, it is crucial to understand the adaptations of these microbial spacefarers in spaceflight conditions. We aimed to elucidate the genetic determinants of microbial survival in space using a pan-genome analysis of 12 genera cultured from the International Space Station (ISS) from 2017 to 2018. Analysis was performed on each of the genera individually with terrestrial analogs to identify the core and accessory genomes of the spaceflight and terrestrial strains. We then compared the flight and terrestrial core and accessory genomes for each genera using a Bray-Curtis index and visualized the resulting dissimilarity using an Non-Metric Dimensional Scaling plot. The core proteins available in only the spaceflight organisms were then manually characterized for function and genomic location. In every core genome comparison in each genus, there was significant dissimilarity in the core of the spaceflight organisms when compared to the terrestrial organisms. This trend was present in some of the accessory genomes, but was not ubiquitous. Functional analysis of the core content of the ISS genomes showed the majority of genes unique to the core were clustered by location. These gene clusters suggested a set of genetic determinants confer survival in spacecraft-built environments, notably through the uptake of extracellular DNA such as bacteriophage and plasmids. The clear difference between spaceflight and terrestrial microorganisms shows that spaceflight conditions are selective, which has long term implications for their human hosts and environments.

MoBE↗
NASA NTRS1991

A deficiency of the homeotic complex of the beetle Tribolium

In Drosophila, the establishment of regional commitments along most of the anterior/posterior axis of the developing embryo depends on two clusters of homeotic genes: the Antennapedia complex (ANT-C) and the bithorax complex (BX-C). The red flour beetle has a single complex (HOM-C) representing the homologues of the ANT-C and BX-C in juxtaposition. Beetles trans-heterozygous for two particular HOM-C mutations spontaneously generate a large deficiency, presumably by an exchange within the common region of two overlapping inversions. Genetic and molecular results indicate that this deficiency spans at least the interval between the Deformed and abdominal-A homologues. In deficiency homozygous embryos, all gnathal, thoracic and abdominal segments develop antennal appendages, suggesting that a gene(s) has been deleted that acts to distinguish trunk from head. There is no evidence that beetles have a homologue of the segmentation gene fushi tarazu of similar genomic location and function. On the basis of the genetic tractability, convenient genome size and organization of Tribolium, and its relatively long phylogenetic divergence from Drosophila (>300 million years), we have integrated developmental genetic and molecular analyses of the HOM-C. We isolated about 70 mutations in the complex representing at least six complementation groups. The homeotic phenotypes of adults and lethal embryos lead us to believe that these beetle genes are homologous with the Drosophila genes indicated in Fig. 1 (see text).

NASA Program NSCORT↗
NASA NTRS1999

Archaea: From Genomics to Physiology and the Origin of Life

This document represents a report on a meeting about Archaea. The meeting had an unusually diversified mix of topics all related to Archaea highlighting their differences and similarities with other kingdoms of life. Thus, a large number of scientists from others areas of biology participated in this conference. One-third of the speakers (11 of 33) represented laboratories whose main interests have not been archaea and who have not previously participated in similar symposia or workshops. Thus, this symposium provided a unique opportunity for archaeal researchers to interact in a wider forum. Because of the broad range of topics covered, the conference also introduced many of the participants to new areas of archaeal research. The discussions of genomics, molecular mechanisms of transcription, metabolic pathways and evolution were at a very high level. Talks and posters provided detailed discussions of the state of the current knowledge in RNA processing, transcriptional initiation, chromatin structure, aminoacyl-tRNA synthetases, autotrophic CO2 fixation, Upid biosynthesis and a wide range of other topics. In addition to providing overviews, major areas of scientific argument were clearly delineated, particularly in the discussions of genomics and evolution. Some of the questions raised included: how representative are individual gene trees of organismal evolution, how prevalent is horizontal evolution, how reliable are functional assignments in genomics? On these topics, the different points of view were well represented. The future of any field depends on the enthusiasm and intellectual engagement of young scientists working in the area. Therefore, the participation of 29 graduate and postdoctoral students (out of about 135 participants) was a highlight of the meeting. This was the consequence of funding contributions by NSF and NASA.

Vothknecht, Ute C.↗
NASA NTRS2003

Resistance of virus to extinction on bottleneck passages: study of a decaying and fluctuating pattern of fitness loss

RNA viruses display high mutation rates and their populations replicate as dynamic and complex mutant distributions, termed viral quasispecies. Repeated genetic bottlenecks, which experimentally are carried out through serial plaque-to-plaque transfers of the virus, lead to fitness decrease (measured here as diminished capacity to produce infectious progeny). Here we report an analysis of fitness evolution of several low fitness foot-and-mouth disease virus clones subjected to 50 plaque-to-plaque transfers. Unexpectedly, fitness decrease, rather than being continuous and monotonic, displayed a fluctuating pattern, which was influenced by both the virus and the state of the host cell as shown by effects of recent cell passage history. The amplitude of the fluctuations increased as fitness decreased, resulting in a remarkable resistance of virus to extinction. Whereas the frequency distribution of fitness in control (independent) experiments follows a log-normal distribution, the probability of fitness values in the evolving bottlenecked populations fitted a Weibull distribution. We suggest that multiple functions of viral genomic RNA and its encoded proteins, subjected to high mutational pressure, interact with cellular components to produce this nontrivial, fluctuating pattern.

Serial Passage↗
NASA NTRS2015

Research from the NASA Twins Study and Omics in Support of Mars Missions

The NASA Twins Study, NASA's first foray into integrated omic studies in humans, illustrates how an integrated omics approach can be brought to bear on the challenges to human health and performance on a Mars mission. The NASA Twins Study involves US Astronaut Scott Kelly and his identical twin brother, Mark Kelly, a retired US Astronaut. No other opportunity to study a twin pair for a prolonged period with one subject in space and one on the ground is available for the foreseeable future. A team of 10 principal investigators are conducting the Twins Study, examining a very broad range of biological functions including the genome, epigenome, transcriptome, proteome, metabolome, gut microbiome, immunological response to vaccinations, indicators of atherosclerosis, physiological fluid shifts, and cognition. A novel aspect of the study is the integrated study of molecular, physiological, cognitive, and microbiological properties. Major sample and data collection from both subjects for this study began approximately six months before Scott Kelly's one year mission on the ISS, continue while Scott Kelly is in flight and will conclude approximately six months after his return to Earth. Mark Kelly will remain on Earth during this study, in a lifestyle unconstrained by this study, thereby providing a measure of normal variation in the properties being studied. An overview of initial results and the future plans will be described as well as the technological and ethical issues raised for spaceflight studies involving omics.

Kundrot, C.↗
NASA NTRS2017

Novel Approach to Quantification of Telomere Length with Direct Nanopore Sequencing and PCR Amplification

The ends of human chromosomes contain telomeres, or tandem arrays of repeating DNA sequences capped by multiple associated proteins that protect chromosomal ends from degradation. Telomeres function to preserve genomic stability by preventing natural chromosomal ends from being recognized as broken DNA double-strand breaks and triggering inappropriate DNA damage responses. Mounting evidence shows telomere length is an inherited trait that decreases with cellular division and normal aging. In addition, telomere length also appears to be influenced by other factors such as cellular oxidative stress, radiation and mechanical unloading of tissues as in microgravity. To measure these potential effects of the space environment on telomere lengths and cellular aging and regenerative potential we developed a novel telomere measurement approach based on nanopore sequencing of PCR amplified bar-coded chromosome termini. Specifically, telomeres can be directly enriched using barcode sequences ligated to the end of a free end- repaired telomere using the WetLab-2 facility SmartCycler on ISS. Prior to the ligation and amplification protocol a proteinase K digestion of capping proteins followed by a single 95-degree C heat denaturation of the protease is included. After digestion and bar-code ligation, PCR amplification will initiate with the ligated barcoded sequence, suppressing amplification of intra-genomic fragments and resulting in long read barcoded telomere amplicons including the nanopore motor protein sequences. Purified PCR amplicons are then used for nanopore sequencing library generation by simple addition of motor proteins and sequencing library is loaded into the MinION nanopore DNA-sequencer. Amplicon sequence reads from the nanopore device can be base-called quickly on ISS due to barcoding ligation and subsequent PCR amplification enhancing the telomere sequence resolution. If successfully implemented on ISS this technique will provide a novel means of measuring regenerative ability of somatic stem cells in astronauts, and of determining whether spaceflight in microgravity alters their telomere lengths and causes premature cellular aging.

Ma, Kristin R.↗
NASA NTRS2007

Deep Space Network Scheduling Using Evolutionary Computational Methods

The paper presents the specific approach taken to formulate the problem in terms of gene encoding, fitness function, and genetic operations. The genome is encoded such that a subset of the scheduling constraints is automatically satisfied. Several fitness functions are formulated to emphasize different aspects of the scheduling problem. The optimal solutions of the different fitness functions demonstrate the trade-off of the scheduling problem and provide insight into a conflict resolution process.

Deep Space Network (DSN)↗