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At least 163 records · Page 9
All sourcesNASA NTRSDOE OSTI
NASA NTRS2015

Wetlab-2 - Quantitative PCR Tools for Spaceflight Studies of Gene Expression Aboard the International Space Station

Wetlab-2 is a research platform for conducting real-time quantitative gene expression analysis aboard the International Space Station. The system enables spaceflight genomic studies involving a wide variety of biospecimen types in the unique microgravity environment of space. Currently, gene expression analyses of space flown biospecimens must be conducted post flight after living cultures or frozen or chemically fixed samples are returned to Earth from the space station. Post-flight analysis is limited for several reasons. First, changes in gene expression can be transient, changing over a timescale of minutes. The delay between sampling on Earth can range from days to months, and RNA may degrade during this period of time, even in fixed or frozen samples. Second, living organisms that return to Earth may quickly re-adapt to terrestrial conditions. Third, forces exerted on samples during reentry and return to Earth may affect results. Lastly, follow up experiments designed in response to post-flight results must wait for a new flight opportunity to be tested.

ISS research platform↗
DOE OSTI2012

Dose–response analysis of phthalate effects on gene expression in rat whole embryo culture

The rat postimplantation whole embryo culture (WEC) model serves as a potential screening tool for developmental toxicity. In this model, cultured rat embryos are exposed during early embryogenesis and evaluated for morphological effects. The integration of molecular-based markers may lead to improved objectivity, sensitivity and predictability of WEC in assessing developmental toxic properties of compounds. In this study, we investigated the concentration-dependent effects of two phthalates differing in potency, mono(2-ethylhexyl) phthalate (MEHP) and monomethyl phthalate (MMP, less toxic), on the transcriptome in WEC to examine gene expression in relation with dysmorphogenesis. MEHP was more potent than MMP in inducing gene expression changes as well as changes on morphology. MEHP induced significant enrichment of cholesterol/lipid/steroid (CLS) metabolism and apoptosis pathways which was associated with developmental toxicity. Regulation of genes within CLS metabolism pathways represented the most sensitive markers of MEHP exposure, more sensitive than classical morphological endpoints. As shown in direct comparisons with toxicogenomic in vivo studies, alterations in the regulation of CLS metabolism pathways has been previously identified to be associated with developmental toxicity due to phthalate exposure in utero. Our results support the application of WEC as a model to examine relative phthalate potency through gene expression and morphological responses. Additionally, our results further define the applicability domain of the WEC model for developmental toxicological investigations. -- Highlights: ► We examine the effect of two phthalates on gene expression and morphology in WEC. ► MEHP is more potent than MMP in inducing gene expression changes and dysmorphogenesis. ► MEHP significantly disrupts cholesterol metabolism pathways in a dose-dependent manner. ► Specific phthalate-related mechanisms in WEC are relevant to mechanisms in vivo.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

High E6 Gene Expression Predicts for Distant Metastasis and Poor Survival in Patients With HPV-Positive Oropharyngeal Squamous Cell Carcinoma

Purpose: Patients with human papillomavirus (HPV)–positive oropharyngeal squamous cell carcinoma (OPSCC) have a favorable prognosis. As a result, de-escalation clinical trials are under way. However, approximately 10% of patients will experience distant recurrence even with standard-of-care treatment. Here, we sought to identify novel biomarkers to better risk-stratify HPV-positive patients with OPSCC. Methods and Materials: Gene expression profiling by RNA sequencing (RNA-seq) and quantitative polymerase chain reaction was performed on HPV-positive OPSCC primary tumor specimens from patients with and without distant metastasis (DM). Results: RNA-seq analysis of 39 HPV-positive OPSCC specimens revealed that patients with DM had 2-fold higher E6 gene expression levels than did patients without DM (P=.029). This observation was confirmed in a validation cohort comprising 93 patients with HPV-positive OPSCC. The mean normalized E6 expression level in the 17 recurring primary specimens was 13 ± 2 compared with 8 ± 1 in the remaining 76 nonrecurring primaries (P=.001). Receiver operating characteristic analysis established an E6 expression level of 7.3 as a cutoff for worse recurrence-free survival (RFS). Patients from this cohort with high E6 gene expression (E6-high) (n=51, 55%) had more cancer-related deaths (23% vs 2%, P<.001) and DM (26% vs 5%, P<.001) than did patients with low E6 gene expression (E6-low) (n=42, 45%). Kaplan-Meier survival analysis revealed that E6-high had worse RFS (95% vs 69%, P=.004) and cancer-specific survival (97% vs 79%, P=.007). E6-high maintained statistical significance in multivariate regression models balancing surgery, chemotherapy, nodal stage, and smoking status. Gene set enrichment analysis demonstrated that tumors with high E6 expression were associated with P53, epidermal growth factor receptor, activating transcription factor-2, and transforming growth factor-β signaling pathways. Conclusion: High E6 gene expression level identifies HPV-positive OPSCC patients with 5-fold greater risk of distant disease recurrence and worse cancer-specific survival. Validation in a multi-institutional prospective clinical trial is required to assess the utility of E6 gene expression as a clinically useful prognostic biomarker.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Sex-based differences in gene expression in hippocampus following postnatal lead exposure

The influence of sex as an effect modifier of childhood lead poisoning has received little systematic attention. Considering the paucity of information available concerning the interactive effects of lead and sex on the brain, the current study examined the interactive effects of lead and sex on gene expression patterns in the hippocampus, a structure involved in learning and memory. Male or female rats were fed either 1500 ppm lead-containing chow or control chow for 30 days beginning at weaning.Blood lead levels were 26.7 {+-} 2.1 {mu}g/dl and 27.1 {+-} 1.7 {mu}g/dl for females and males, respectively. The expression of 175 unique genes was differentially regulated between control male and female rats. A total of 167 unique genes were differentially expressed in response to lead in either males or females. Lead exposure had a significant effect without a significant difference between male and female responses in 77 of these genes. In another set of 71 genes, there were significant differences in male vs. female response. A third set of 30 genes was differentially expressed in opposite directions in males vs. females, with the majority of genes expressed at a lower level in females than in males. Highly differentially expressed genes in males and females following lead exposure were associated with diverse biological pathways and functions. These results show that a brief exposure to lead produced significant changes in expression of a variety of genes in the hippocampus and that the response of the brain to a given lead exposure may vary depending on sex. - Highlights: > Postnatal lead exposure has a significant effect on hippocampal gene expression patterns. > At least one set of genes was affected in opposite directions in males and females. > Differentially expressed genes were associated with diverse biological pathways.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Genetics of gene expression in the aging human brain reveal TDP-43 proteinopathy pathophysiology

Genetic variants that control distant gene expression are highly relevant for disease mechanisms but remain poorly charaterized. Here, leveraging the modular structure of gene coexpression in the aging human brain, we performed genome-wide association studies of gene coexpression modules and identified TMEM106B and RBFOX1 as module quantitative trait loci (modQTLs). The TMEM106B modQTL is a known risk locus of neurodegenerative TDP-43 proteinopathy and has a large-scale dominant transcriptomic effect including lysosomal and splicing dysregulation, recapitulating TDP-43 pathophysiology. Further, a locus in another TDP-43 proteinopathy risk gene, GRN, shows similar transcriptomic effects. TMEM106B and APOE/amyloid-ß converge on altered myelination/lysosomal gene expression, and jointly promote limbic-predominant age-related TDP-43 encephalopathy neuropathological change. Thus, genetic architecture of distant gene expression in the aging human brain elucidates TDP-43 proteinopathy pathophysiology.

Yang, Hyun-Sik↗
NASA NTRS2017

Ionizing Radiation Affects Gene Expression in Mouse Skin and Bone

Future long-duration space exploration beyond low earth orbit will increase human exposure to space radiation and microgravity conditions as well as associated risks to skeletal health. In animal studies, radiation exposure (greater than 1 Gy) is associated with pathological changes in bone structure, enhanced bone resorption, reduced bone formation and decreased bone mineral density, which can lead to skeletal fragility. Definitive measurements and detection of bone loss typically require large and specialized equipment which can make their application to long duration space missions logistically challenging. Towards the goal of developing non-invasive and less complicated monitoring methods to predict astronauts' health during spaceflight, we examined whether radiation induced gene expression changes in skin may be predictive of the responses of skeletal tissue to radiation exposure. We examined oxidative stress and growth arrest pathways in mouse skin and long bones by measuring gene expression levels via quantitative polymerase chain reaction (qPCR) after exposure to total body irradiation (IR). To investigate the effects of irradiation on gene expression, we used skin and femora (cortical shaft) from the following treatment groups: control (normally loaded, sham-irradiated), and IR (0.5 Gy 56Fe 600 MeV/n and 0.5 Gy 1H 150 MeV/n), euthanized at one and 11 days post-irradiation (IR). To determine the extent of bone loss, tibiae were harvested and cancellous microarchitecture in the proximal tibia quantified ex vivo using microcomputed tomography (microCT). Statistical analysis was performed using Student's t-test. At one day post-IR, expression of FGF18 in skin was significantly greater (3.8X) than sham-irradiated controls, but did not differ at 11 days post IR. Expression levels of other genes associated with antioxidant response (Nfe2l2, FoxO3 and Sod1) and the cell cycle (Trp53, Cdkn1a, Gadd45g) did not significantly differ between the control and IR groups at either time point. Radiation exposure resulted in a 27.0% increase in FGF18-positive hair follicles at one day post-IR and returned to basal levels at 11 days post-IR. A similar trend was observed from FGF18 gene expression analysis of skin. In bone (femora), there was an increase in the expression of the pro-osteoclastogenic cytokine, MCP-1, one day after IR compared to non-irradiated controls. FGF18 expression in skin and MCP- 1 expression in bone were found to be positively correlated (P less than 0.002, r=0.8779). Further, microcomputed tomography analysis of tibia from these animals showed reduced cancellous bone volume (-9.9%) at 11 days post- IR. These results suggest that measurements of early radiation induced changes in FGF18 gene expression in skin may have value for predicting subsequent loss of cancellous bone mass. Further research may lead to the development of a relatively simple diagnostic tool for bone loss, with the advantage that hair follicles and skin are relatively easy to acquire from human subjects.

space radiation↗
DOE OSTI2011

Unifying Gene Expression Measures from Multiple Platforms Using Factor Analysis

In the Cancer Genome Atlas (TCGA) project, gene expression of the same set of samples is measured multiple times on different microarray platforms. There are two main advantages to combining these measurements. First, we have the opportunity to obtain a more precise and accurate estimate of expression levels than using the individual platforms alone. Second, the combined measure simplifies downstream analysis by eliminating the need to work with three sets of expression measures and to consolidate results from the three platforms. We propose to use factor analysis (FA) to obtain a unified gene expression measure (UE) from multiple platforms. The UE is a weighted average of the three platforms, and is shown to perform well in terms of accuracy and precision. In addition, the FA model produces parameter estimates that allow the assessment of the model fit. The R code is provided in File S2. Gene-level FA measurements for the TCGA data sets are available from http://tcga-data.nci.nih.gov/docs/publications/unified_expression/.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Exact and efficient hybrid Monte Carlo algorithm for accelerated Bayesian inference of gene expression models from snapshots of single-cell transcripts

Single cells exhibit a significant amount of variability in transcript levels, which arises from slow, stochastic transitions between gene expression states. Elucidating the nature of these states and understanding how transition rates are affected by different regulatory mechanisms require state-of-the-art methods to infer underlying models of gene expression from single cell data. A Bayesian approach to statistical inference is the most suitable method for model selection and uncertainty quantification of kinetic parameters using small data sets. However, this approach is impractical because current algorithms are too slow to handle typical models of gene expression. To solve this problem, we first show that time-dependent mRNA distributions of discrete-state models of gene expression are dynamic Poisson mixtures, whose mixing kernels are characterized by a piecewise deterministic Markov process. Here, we combined this analytical result with a kinetic Monte Carlo algorithm to create a hybrid numerical method that accelerates the calculation of time-dependent mRNA distributions by 1000-fold compared to current methods. We then integrated the hybrid algorithm into an existing Monte Carlo sampler to estimate the Bayesian posterior distribution of many different, competing models in a reasonable amount of time. We demonstrate that kinetic parameters can be reasonably constrained for modestly sampled data sets if the model is known a priori. If there are many competing models, Bayesian evidence can rigorously quantify the likelihood of a model relative to other models from the data. We demonstrate that Bayesian evidence selects the true model and outperforms approximate metrics typically used for model selection.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Identification of a repressor and an activator of azoreductase gene expression in Pseudomonas putida and Xanthomonas oryzae

Highlights: • Transcriptional regulators of azoreductase of P. putida and X. oryzae were found. • They were named AzoPR (for P. putida) and AzoXR (for X. oryzae). • Despite 51% amino acid identity, AzoPR is a repressor, while AzoXR is an activator. • They respond differently to methyl red which acts as an inducer of gene expression. Genes responsible for the production of azoreductase enzymes in 2 gram-negative bacteria, the soil bacterium Pseudomonas putida (AzoP) and the plant pathogen Xanthomonas oryzae (AzoX), were identified. The deduced amino acid sequences of AzoP and AzoX, share 46% amino acid identity to each other. Two different bacterial transcription factors, a repressor (AzoPR) and an activator (AzoXR), in P. putida and X. oryzae, respectively, were found to be divergently oriented to their respective azoreductase genes. Both regulators are LysR-type transcriptional regulators (LTTR) that respond to the azo dye inducer, methyl red (MR). AzoPR represses transcription of azoP in P. putida, which is reversed when cells are exposed to MR. Interestingly, in X. oryzae, AzoXR positively regulates azoX transcription upon MR induction. Moreover, despite their similarity, with 51% amino acid sequence identity, azoPR and azoXR are expressed differently in response to MR. The transcription of azoPR is increased in a dye concentration-dependent manner, while azoXR transcription is constitutive and relatively higher than azoPR. Both regulators are autoregulatory. Gel mobility shift assays (EMSA) verified the binding between the regulators and their corresponding promoter regions. Additionally, binding only occurred under reduced conditions in the presence of 0.5 mM dithiothreitol (DTT), indicating that the proteins are active in their reduced form.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Macromolecular Crowding Induces Spatial Correlations That Control Gene Expression Bursting Patterns

Recent superresolution microscopy studies in E. coli demonstrate that the cytoplasm has highly variable local concentrations where macromolecular crowding plays a central role in establishing membrane-less compartmentalization. This spatial inhomogeneity significantly influences molecular transport and association processes central to gene expression. Yet, little is known about how macromolecular crowding influences gene expression bursting—the episodic process where mRNA and proteins are produced in bursts. Here, we simultaneously measured mRNA and protein reporters in cell-free systems, showing that macromolecular crowding decoupled the well-known relationship between fluctuations in the protein population (noise) and mRNA population statistics. Crowded environments led to a 10-fold increase in protein noise even though there were only modest changes in the mRNA population and fluctuations. Instead, cell-like macromolecular crowding created an inhomogeneous spatial distribution of mRNA (“spatial noise”) that led to large variability in the protein production burst size. As a result, the mRNA spatial noise created large temporal fluctuations in the protein population. Furthermore, these results highlight the interplay between macromolecular crowding, spatial inhomogeneities, and the resulting dynamics of gene expression, and provide insights into using these organizational principles in both cell-based and cell-free synthetic biology.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Dynamic BAF chromatin remodeling complex subunit inclusion promotes temporally distinct gene expression programs in cardiogenesis

Chromatin remodeling complexes instruct cellular differentiation and lineage specific transcription. The BRG1/BRM-associated factor (BAF) complexes are important for several aspects of differentiation. We show that the catalytic subunit gene Brg1 has a specific role in cardiac precursors (CPs) to initiate cardiac gene expression programs and repress non-cardiac expression. Using immunopurification with mass spectrometry, we have determined the dynamic composition of BAF complexes during mammalian cardiac differentiation, identifying several cell-type specific subunits. We focused on the CP- and cardiomyocyte (CM)-enriched subunits BAF60c (SMARCD3) and BAF170 (SMARCC2). Baf60c and Baf170 co-regulate gene expression with Brg1 in CPs, and in CMs their loss results in broadly deregulated cardiac gene expression. BRG1, BAF60c and BAF170 modulate chromatin accessibility, to promote accessibility at activated genes while closing chromatin at repressed genes. BAF60c and BAF170 are required for proper BAF complex composition, and BAF170 loss leads to retention of BRG1 at CP-specific sites. Thus, dynamic interdependent BAF complex subunit assembly modulates chromatin states and thereby participates in directing temporal gene expression programs in cardiogenesis.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2011

Radiation response and regulation of apoptosis induced by a combination of TRAIL and CHX in cells lacking mitochondrial DNA: A role for NF-{kappa}B-STAT3-directed gene expression

Mitochondrial DNA depleted ({rho}{sup 0}) human skin fibroblasts (HSF) with suppressed oxidative phosphorylation were characterized by significant changes in the expression of 2100 nuclear genes, encoding numerous protein classes, in NF-{kappa}B and STAT3 signaling pathways, and by decreased activity of mitochondrial death pathway, compared to the parental {rho}{sup +} HSF. In contrast, the extrinsic TRAIL/TRAIL-Receptor mediated death pathway remained highly active, and exogenous TRAIL in a combination with cycloheximide (CHX) induced higher levels of apoptosis in {rho}{sup 0} cells compared to {rho}{sup +} HSF. Global gene expression analysis using microarray and qRT-PCR demonstrated that mRNA expression levels of many growth factors and their adaptor proteins (FGF13, HGF, IGFBP4, IGFBP6, and IGFL2), cytokines (IL6, {Oota}L17{Beta}, {Oota}L18, {Oota}L19, and {Oota}L28{Beta}) and cytokine receptors (IL1R1, IL21R, and IL31RA) were substantially decreased after mitochondrial DNA depletion. Some of these genes were targets of NF-{kappa}B and STAT3, and their protein products could regulate the STAT3 signaling pathway. Alpha-irradiation further induced expression of several NF-{kappa}B/STAT3 target genes, including IL1A, IL1B, IL6, PTGS2/COX2 and MMP12, in {rho}{sup +} HSF, but this response was substantially decreased in {rho}{sup 0} HSF. Suppression of the IKK-NF-{kappa}B pathway by the small molecular inhibitor BMS-345541 and of the JAK2-STAT3 pathway by AG490 dramatically increased TRAIL-induced apoptosis in the control and irradiated {rho}{sup +} HSF. Inhibitory antibodies against IL6, the main activator of JAK2-STAT3 pathway, added into the cell media, also increased TRAIL-induced apoptosis in HSF, especially after alpha-irradiation. Collectively, our results indicated that NF-{kappa}B activation was partially lost in {rho}{sup 0} HSF resulting in downregulation of the basal or radiation-induced expression of numerous NF-{kappa}B targets, further suppressing IL6-JAK2-STAT3 that in concert with NF-{kappa}B regulated protection against TRAIL-induced apoptosis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Regulatory Tools for Controlling Gene Expression in Cyanobacteria

Cyanobacteria are attractive hosts for converting carbon dioxide and sunlight into desirable chemical products. To engineer these organisms and manipulate their metabolic pathways, the biotechnology community has developed genetic tools to control gene expression. Many native cyanobacterial promoters and related sequence elements have been used to regulate genes of interest, and heterologous tools that use non-native small molecules to induce gene expression have been demonstrated. Overall, IPTG-based induction systems seem to be leaky and initially demonstrate small dynamic ranges in cyanobacteria. Consequently, a variety of other induction systems have been optimized to enable tighter control of gene expression. Tools require significant optimization because they function quite differently in cyanobacteria when compared to analogous use in model heterotrophs. We hypothesize that these differences are due to fundamental differences in physiology between organisms. This review is not intended to summarize all known products made in cyanobacteria nor the performance (titer, rate, yield) of individual strains, but instead will focus on the genetic tools and the inherent aspects of cellular physiology that influence gene expression in cyanobacteria.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Bayesian filtering for model predictive control of stochastic gene expression in single cells

This study describes a method for controlling the production of protein in individual cells using stochastic models of gene expression. By combining modern microscopy platforms with optogenetic gene expression, experimentalists are able to accurately apply light to individual cells, which can induce protein production. Here we use a finite state projection based stochastic model of gene expression, along with Bayesian state estimation to control protein copy numbers within individual cells. We compare this method to previous methods that use population based approaches. We also demonstrate the ability of this control strategy to ameliorate discrepancies between the predictions of a deterministic model and stochastic switching system.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2011

Reduction in Inflammatory Gene Expression in Skeletal Muscle from Roux-en-Y Gastric Bypass Patients Randomized to Omentectomy

To examine the effects of Roux-en-Y gastric bypass (RYGB) surgery with and without laparoscopic removal of omental fat (omentectomy) on the temporal gene expression profiles of skeletal muscle. Previously reported were the whole-body metabolic effects of a randomized, single-blinded study in patients receiving RYGB surgery stratified to receive or not receive omentectomy. In this follow up study we report on changes in skeletal muscle gene expression in a subset of 21 patients, for whom biopsies were collected preoperatively and at either 6 months or 12 months postoperatively. RNA isolated from skeletal muscle biopsies of 21 subjects (8 without omentectomy and 13 with omentectomy) taken before RYGB or at 6 and 12 months postoperatively were subjected to gene expression profiling via Exon 1.0 S/T Array and Taqman Low Density Array. Robust Multichip Analysis and gene enrichment data analysis revealed 84 genes with at least a 4-fold expression difference after surgery. At 6 and 12 months the RYGB with omentectomy group displayed a greater reduction in the expression of genes associated with skeletal muscle inflammation (ANKRD1, CDR1, CH25H, CXCL2, CX3CR1, IL8, LBP, NFIL3, SELE, SOCS3, TNFAIP3, and ZFP36) relative to the RYGB nonomentectomy group. Expressions of IL6 and CCL2 were decreased at all postoperative time points. There was differential expression of genes driving protein turnover (IGFN1, FBXW10) in both groups over time and increased expression of PAAF1 in the non-omentectomy group at 12 months. Evidence for the activation of skeletal muscle satellite cells was inferred from the up-regulation of HOXC10. The elevated post-operative expression of 22 small nucleolar RNAs and the decreased expression of the transcription factors JUNB, FOS, FOSB, ATF3 MYC, EGR1 as well as the orphan nuclear receptors NR4A1, NR4A2, NR4A3 suggest dramatic reorganizations at both the cellular and genetic levels. These data indicate that RYGB reduces skeletal muscle inflammation, and removal of omental fat further amplifies this response.

60 APPLIED LIFE SCIENCES↗
NASA NTRSDate not supplied

Differential Gene Expression in A Cross-Feeding Two-Species Model Microbial Community Under Simulated Microgravity and Deep-Space Radiation

A long-term goal of space biology is to understand interspecies microbial interactions in space. Presently, little is known about the combined effect of microgravity and ionizing radiation on bacterial community response when species are interdependent through exchange of metabolites in fluid medium (cross-feeding). Microgravity is expected to slow interspecies mass transfer and growth in cross-feeding communities in the low-shear, diffusion-limited environment, while ionizing radiation may influence stress response to direct (DNA damage) and indirect damage (ROS). Using a well-understood, two-species (Escherichia coli and Salmonella enterica) microbial community engineered to be a model for studying cross-feeding, we simulated galactic cosmic rays (GCRsim) and microgravity to test the hypothesis: exposure to ionizing radiation causes cell damage or stress, altering transcriptomic community responses in metabolically interdependent cells, which is exacerbated by microgravity. We expect to see differential gene expression between cross-feeding and non-cross-feeding communities. We measured GCRsim effects on growth and gene expression in well-mixed versus simulated-microgravity conditions and in cross-feeding and non-cross-feeding medium. Microbial cultures were inoculated into liquid medium in rotating wall vessels (RWV) with different rotation rates: 5 RPM (simulated microgravity) and 50 RPM (well-mixed). The E. coli-S. enterica consortium, under simulated microgravity, were exposed to 500 mGy of Simplified 5-ion Galactic Cosmic Ray Simulation for 2 hours at Brookhaven National Lab. We harvested samples 40 minutes after irradiation for extraction and sequencing (NASA GeneLab). Here we present the differential gene expression analysis results, which reveal altered transcriptomic community responses, even where growth rate differences are not observed. Gene expression of these actively metabolizing microbial communities in GCRsim may illuminate molecular mechanisms of microbial interactions in space. Understanding how microbial community gene expression, metabolism, and other cellular processes are influenced by spaceflight stressors can inform the use of microbes in human life support for low Earth orbit missions and beyond.

microgravity↗
NASA NTRS2016

Network Security via Biometric Recognition of Patterns of Gene Expression

Molecular biology provides the ability to implement forms of information and network security completely outside the bounds of legacy security protocols and algorithms. This paper addresses an approach which instantiates the power of gene expression for security. Molecular biology provides a rich source of gene expression and regulation mechanisms, which can be adopted to use in the information and electronic communication domains. Conventional security protocols are becoming increasingly vulnerable due to more intensive, highly capable attacks on the underlying mathematics of cryptography. Security protocols are being undermined by social engineering and substandard implementations by IT organizations. Molecular biology can provide countermeasures to these weak points with the current security approaches. Future advances in instruments for analyzing assays will also enable this protocol to advance from one of cryptographic algorithms to an integrated system of cryptographic algorithms and real-time expression and assay of gene expression products.

cybersecurity↗
DOE OSTI2021

Single molecule-based fliFISH validates radial and heterogeneous gene expression patterns in pancreatic islet ß cells

Single cell RNA sequencing (scRNA-Seq) technologies have greatly enhanced our understanding of islet cell transcriptomes and have revealed the existence of ß cell heterogeneity. However, comparison of scRNA-Seq datasets from different groups have highlighted inconsistencies in gene expression patterns, primarily due to variable detection of lower abundance transcripts. Furthermore, such analyses are unable to uncover the spatial organization of heterogeneous gene expression. Here we used fluctuation localization imaging-based fluorescence in situ hybridization (fliFISH) to quantify transcripts in single cells in mouse pancreatic islet sections. We compared the expression patterns of Insulin 2 (Ins2) with Mafa and Ucn3 – two genes expressed in ß cells as they mature, as well as Rgs4 – a factor with variably reported expression in the islet. This approach accurately quantified transcripts across a wide range of expression levels - from single copies to over hundred copies per cell in one islet. Importantly, fliFISH allowed evaluation of transcript heterogeneity in the spatial context of an intact islet. These studies confirm the existence of a high degree of heterogeneous gene expression levels within the islet and highlight relative and radial expression patterns that likely reflect distinct ß cell maturation states along the radial axis of the islet.

Li, Fangjia↗