Search NASA⌕ Search

SEARCH · Search NASA

Results for “Cell Death”

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.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3
All sourcesNASA NTRSDOE OSTI
NASA NTRS2002

Effects of Gravity on Cell Movement and Development

The main purpose of this project was to understand how the migration and growth of cultured cells respond to mechanical forces. We have made significant progress on all the proposed aims. The most important discoveries are that changes in the environmental mechanical input, such as during space flight, can induce profound changes in cell migration, growth, and programmed cell death. In addition, using genetically engineered cells, we have gained important insight into the molecular mechanism underlying such mechanosensing processes. The results are summarized.

Wang, Yu-Li↗
NASA NTRS2003

Radiation-induced genomic instability and its implications for radiation carcinogenesis

Radiation-induced genomic instability is characterized by an increased rate of genetic alterations including cytogenetic rearrangements, mutations, gene amplifications, transformation and cell death in the progeny of irradiated cells multiple generations after the initial insult. Chromosomal rearrangements are the best-characterized end point of radiation-induced genomic instability, and many of the rearrangements described are similar to those found in human cancers. Chromosome breakage syndromes are defined by chromosome instability, and individuals with these diseases are cancer prone. Consequently, chromosomal instability as a phenotype may underlie some fraction of those changes leading to cancer. Here we attempt to relate current knowledge regarding radiation-induced chromosome instability with the emerging molecular information on the chromosome breakage syndromes. The goal is to understand how genetic and epigenetic factors might influence the onset of chromosome instability and the role of chromosomal instability in carcinogenesis.

Review, Tutorial↗
NASA NTRS1999

Sequence of neuron origin and neocortical laminar fate: relation to cell cycle of origin in the developing murine cerebral wall

Neurons destined for each region of the neocortex are known to arise approximately in an "inside-to-outside" sequence from a pseudostratified ventricular epithelium (PVE). This sequence is initiated rostrolaterally and propagates caudomedially. Moreover, independently of location in the PVE, the neuronogenetic sequence in mouse is divisible into 11 cell cycles that occur over a 6 d period. Here we use a novel "birth hour" method that identifies small cohorts of neurons born during a single 2 hr period, i.e., 10-20% of a single cell cycle, which corresponds to approximately 1.5% of the 6 d neuronogenetic period. This method shows that neurons arising with the same cycle of the 11 cycle sequence in mouse have common laminar fates even if they arise from widely separated positions on the PVE (neurons of fields 1 and 40) and therefore arise at different embryonic times. Even at this high level of temporal resolution, simultaneously arising cells occupy more than one cortical layer, and there is substantial overlap in the distributions of cells arising with successive cycles. We demonstrate additionally that the laminar representation of cells arising with a given cycle is little if at all modified over the early postnatal interval of histogenetic cell death. We infer from these findings that cell cycle is a neuronogenetic counting mechanism and that this counting mechanism is integral to subsequent processes that determine cortical laminar fate.

NASA Discipline Cell Biology↗
NASA NTRS2007

Multispectral Imaging Broadens Cellular Analysis

Amnis Corporation, a Seattle-based biotechnology company, developed ImageStream to produce sensitive fluorescence images of cells in flow. The company responded to an SBIR solicitation from Ames Research Center, and proposed to evaluate several methods of extending the depth of field for its ImageStream system and implement the best as an upgrade to its commercial products. This would allow users to view whole cells at the same time, rather than just one section of each cell. Through Phase I and II SBIR contracts, Ames provided Amnis the funding the company needed to develop this extended functionality. For NASA, the resulting high-speed image flow cytometry process made its way into Medusa, a life-detection instrument built to collect, store, and analyze sample organisms from erupting hydrothermal vents, and has the potential to benefit space flight health monitoring. On the commercial end, Amnis has implemented the process in ImageStream, combining high-resolution microscopy and flow cytometry in a single instrument, giving researchers the power to conduct quantitative analyses of individual cells and cell populations at the same time, in the same experiment. ImageStream is also built for many other applications, including cell signaling and pathway analysis; classification and characterization of peripheral blood mononuclear cell populations; quantitative morphology; apoptosis (cell death) assays; gene expression analysis; analysis of cell conjugates; molecular distribution; and receptor mapping and distribution.

Source record↗
NASA NTRS2018

Abortive Apoptosis and Its Profound Effects on Radiation, Chemical, and Oncogene-Induced Carcinogenesis

Traditionally apoptosis and the apoptotic machinery have been deemed as anti‐carcinogenic because of their presumed roles in eliminating damaged or unwanted cells. However, recent work from our laboratory and others have shown that the established paradigm is deeply flawed. The fundamental flaw is the assumption that apoptosis, once initiated, is irreversible and invariably leads to cell death. However, there is increasing evidence that cells can survive activation of the apoptotic cascade. This new revelation about abortive apoptotic cells can dramatically change our assessment of the biological roles of apoptosis. In this brief review, we will cover some of the original studies that report the "undead" apoptotic cells and how they lead to unexpected new roles for apoptotic factors in space radiation and other stress induced genetic instability and carcinogenesis. We will also review exciting new discoveries on the association among abortive apoptosis, spontaneous DNA double strand breaks, DNA damage response, and stemness of cancer cells.

Liu, Xinjian↗
DOE OSTI2024

Entire expressed peripheral blood transcriptome in pediatric severe malarial anemia

Abstract This study on severe malarial anemia (SMA: Hb < 6.0 g/dL), a leading global cause of childhood morbidity and mortality, compares the entire expressed whole blood host transcriptome between Kenyan children (3-48 mos.) with non-SMA (Hb ≥ 6.0 g/dL, n = 39) and SMA ( n = 18). Differential expression analyses reveal 1403 up-regulated and 279 down-regulated transcripts in SMA, signifying impairments in host inflammasome activation, cell death, and innate immune and cellular stress responses. Immune cell profiling shows decreased memory responses, antigen presentation, and immediate pathogen clearance, suggesting an immature/improperly regulated immune response in SMA. Module repertoire analysis of blood-specific gene signatures identifies up-regulation of erythroid genes, enhanced neutrophil activation, and impaired inflammatory responses in SMA. Enrichment analyses converge on disruptions in cellular homeostasis and regulatory pathways for the ubiquitin-proteasome system, autophagy, and heme metabolism. Pathway analyses highlight activation in response to hypoxic conditions [Hypoxia Inducible Factor (HIF)−1 target and Reactive Oxygen Species (ROS) signaling] as a central theme in SMA. These signaling pathways are also top-ranking in protein abundance measures and a Ugandan SMA cohort with available transcriptomic data. Targeted RNA-Seq validation shows strong concordance with our entire expressed transcriptome data. These findings identify key molecular themes in SMA pathogenesis, offering potential targets for new malaria therapies.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2011

Summer Research Paper

Certain populations such as chemotherapy patients and atomic bomb survivors have been exposed to ionizing radiation and experience tissue damage and cancer initiation and progression. One cancer that can be initiated from radiation is esophageal squamous cell carcinoma (ESCC), an epithelial cancer that has a survival rate as low as 20%. Researchers have found that when protein tyrosine kinase receptors (RPTK) activate oncogenes, they can create epithelial tumors and cause deadly cancers like ESCC. The RPTK family has one group, MET, that has only two receptors, MET and RON, present in the human body. MET s ligand is the hepatocyte growth factor (HGF) and RON's ligand is the macrophage-stimulating protein (MSP-1). Both HGF and MSP-1 have been shown to activate their receptors and are implicated in certain processes. Since radiation damages cells throughout the biological system, researchers are investigating whether or not HGF and MSP-1 protects or kills certain normal and cancerous cells by being part of cell recovery processes. One research group recently reviewed that the HGF-MET pathway has an important role in the embryonic development in the liver, migration of myogenic precursor cells, regulation of epithelial morphogenesis and growth, and regeneration and protection in tissues. In addition, since the RON receptor is more commonly expressed in cells of epithelial origin, and when activated is part of epithelial cell matrix invasion, dissociation, and migration processes, scientists conclude that RON might be one of the factors causing epithelial cancer initiation in the biological system. In order to examine HGF and MSP-1 s effect on cancer initiation and progression we used two immortalized esophageal epithelial cell lines. One is a normal human cell line (EPC2-hTERT), while the other had a p53 mutation at the 175th amino acid position (EPC2-hTERT-p53(sup R175H)). For this investigation, we used 0(control), 2, and 4 Gray doses of gamma (Cs137) radiation and selected various concentrations from 0-100 ng/mL of HGF and MSP-1 in our assays. Since the HGF and MSP-1 pathways have proliferative roles in epithelial cells, we conducted the MTT proliferation assay to see if either drug enhances or inhibits cell proliferation over time. Also, a MTT cytotoxicity assay was necessary to observe whether the drugs are protecting the cells from radiation and if a trend is occurring depending upon the amount of dose added. In addition, a wound healing assay was done since both drugs have been to known to promote cell motility. Since cell damage occurs when radiation is added, apoptosis and micronuclei assays are vital to see if HGF and MSP-1 increase or decrease cell death and damage in normal and pre-cancerous cells and by how much based on the radiation dosage. Overall, we used the MTT, wound healing, apoptosis and micronuclei assays to investigate the effects ofHGF and MSP-1 on irradiated esophageal epithelial cells.

Patel, Zarana↗
NASA NTRS2005

Electroporation System for Sterilizing Water

A prototype of an electroporation system for sterilizing wastewater or drinking water has been developed. In electroporation, applied electric fields cause transient and/or permanent changes in the porosities of living cells. Electroporation at lower field strengths can be exploited to increase the efficiency of chemical disinfection (as in chlorination). Electroporation at higher field strengths is capable of inactivating and even killing bacteria and other pathogens, without use of chemicals. Hence, electroporation is at least a partial alternative to chlorination. The transient changes that occur in micro-organisms at lower electric-field strengths include significantly increased uptake of ions and molecules. Such increased uptake makes it possible to achieve disinfection at lower doses of chemicals (e.g., chlorine or ozone) than would otherwise be needed. Lower doses translate to lower costs and reduced concentrations of such carcinogenic chemical byproducts as trichloromethane. Higher electric fields cause cell membranes to lose semipermeability and thereby become unable to function as selective osmotic barriers between the cells and the environment. This loss of function is the cause of the cell death at higher electric-field intensities. Experimental evidence does not indicate cell lysis but, rather, combined leaking of cell proteins out of the cells as well as invasion of foreign chemical compounds into the cells. The concept of electroporation is not new: it has been applied in molecular biology and genetic engineering for decades. However, the laboratory-scale electroporators used heretofore have been built around small (400-microliter) cuvettes, partly because the smallness facilitates the generation of electric fields of sufficient magnitude to cause electroporation. Moreover, most laboratory- scale electroporators have been designed for testing static water. In contrast, the treatment cell in the present system is much larger and features a flow-through geometry, such that electric fields strong enough to effect 99.9- percent disinfection can be applied to water flowing in a pipe.

Schlager, Kenneth J.↗
NASA NTRS2008

Radio-sensitization of Prostate Cancer Cells by Monensin Treatment and its associated Gene Expression Profiling Changes

Radio-resistant or recurrent prostate cancer represents a serious health risk for approximately 20%-30% of patients treated with primary radiation therapy for clinically localized prostate cancer. Here, we investigated the effect of monensin on sensitizing radiation mediated cell killing of two radio-resistant prostate cell lines Lncap (P53+ and AR+) and PC3 (P53- and AR-). Treatment with monensin alone (5 micromoles-20 micromoles) showed a significant direct cell killing of Lncap (10-30%), but not PC3 cells. Monensin was also shown to successfully sensitize Lncap cells to X-ray radiation (2Gy-10Gy) mediated cell death, up to 50% of killing with the combined treatment. To better understand the mechanisms of radio-resistance of these two cell lines and their different response to monensin, the apoptosis related gene expression profiles in both cell lines were analyzed using cDNA PCR array. Without any treatment, PC3 showed a much higher expression level of antiapoptosis genes than Lncap in the BCL2 family, the caspase/card family and the TNF ligand/receptor family. At 2 hr after 20 micormolar monensin treatment alone, only the TRAF and CIDE family showed a greater induction in Lncap cells than in PC3. Exposures to 10 Gy X-rays alone of Lncap cells significantly induced gene expression levels in the death and death receptor domain family, the TNF ligand and receptor family, and apoptotic group of BCL2 family; whereas exposures of PC3 induced only the expression of genes in the anti-apoptosis group of CASP and CARD family. Furthermore, we selectively suppressed the expression of several anti-apoptosis genes (BCL-xl, Bcl2A1, BIRC2, BIRC3 and CASP2) in PC3 cells by using the siRNA treatment. Exposure to 10Gy X-rays alone showed an enhanced cell killing (about 15%) in BCL-x1 silenced cells, but not in cells with siRNA treatment targeting other anti-apoptosis genes. We also exposed PC3 cells to protons in the Bragg peak region to compare the effectiveness of cell killing of X-rays. Interestingly, in comparison to X-rays, protons significantly reduced the gene expression in the anti-apoptosis family, suggesting that proton treatment may be more effective for PC3 cells. As a conclusion, monensin was found to sensitize Lncap cells, but not PC3, and over-expression of Bcl-xl cells may be responsible for the radio- or chemo-resistance characteristics of PC3 cells.

Zhang Ye↗
NASA NTRS2001

Extracellular calcium sensing and extracellular calcium signaling

The cloning of a G protein-coupled extracellular Ca(2+) (Ca(o)(2+))-sensing receptor (CaR) has elucidated the molecular basis for many of the previously recognized effects of Ca(o)(2+) on tissues that maintain systemic Ca(o)(2+) homeostasis, especially parathyroid chief cells and several cells in the kidney. The availability of the cloned CaR enabled the development of DNA and antibody probes for identifying the CaR's mRNA and protein, respectively, within these and other tissues. It also permitted the identification of human diseases resulting from inactivating or activating mutations of the CaR gene and the subsequent generation of mice with targeted disruption of the CaR gene. The characteristic alterations in parathyroid and renal function in these patients and in the mice with "knockout" of the CaR gene have provided valuable information on the CaR's physiological roles in these tissues participating in mineral ion homeostasis. Nevertheless, relatively little is known about how the CaR regulates other tissues involved in systemic Ca(o)(2+) homeostasis, particularly bone and intestine. Moreover, there is evidence that additional Ca(o)(2+) sensors may exist in bone cells that mediate some or even all of the known effects of Ca(o)(2+) on these cells. Even more remains to be learned about the CaR's function in the rapidly growing list of cells that express it but are uninvolved in systemic Ca(o)(2+) metabolism. Available data suggest that the receptor serves numerous roles outside of systemic mineral ion homeostasis, ranging from the regulation of hormonal secretion and the activities of various ion channels to the longer term control of gene expression, programmed cell death (apoptosis), and cellular proliferation. In some cases, the CaR on these "nonhomeostatic" cells responds to local changes in Ca(o)(2+) taking place within compartments of the extracellular fluid (ECF) that communicate with the outside environment (e.g., the gastrointestinal tract). In others, localized changes in Ca(o)(2+) within the ECF can originate from several mechanisms, including fluxes of calcium ions into or out of cellular or extracellular stores or across epithelium that absorb or secrete Ca(2+). In any event, the CaR and other receptors/sensors for Ca(o)(2+) and probably for other extracellular ions represent versatile regulators of numerous cellular functions and may serve as important therapeutic targets.

Review↗
NASA NTRS2000

Hair cell recovery in mitotically blocked cultures of the bullfrog saccule

Hair cells in many nonmammalian vertebrates are regenerated by the mitotic division of supporting cell progenitors and the differentiation of the resulting progeny into new hair cells and supporting cells. Recent studies have shown that nonmitotic hair cell recovery after aminoglycoside-induced damage can also occur in the vestibular organs. Using hair cell and supporting cell immunocytochemical markers, we have used confocal and electron microscopy to examine the fate of damaged hair cells and the origin of immature hair cells after gentamicin treatment in mitotically blocked cultures of the bullfrog saccule. Extruding and fragmenting hair cells, which undergo apoptotic cell death, are replaced by scar formations. After losing their bundles, sublethally damaged hair cells remain in the sensory epithelium for prolonged periods, acquiring supporting cell-like morphology and immunoreactivity. These modes of damage appear to be mutually exclusive, implying that sublethally damaged hair cells repair their bundles. Transitional cells, coexpressing hair cell and supporting cell markers, are seen near scar formations created by the expansion of neighboring supporting cells. Most of these cells have morphology and immunoreactivity similar to that of sublethally damaged hair cells. Ultrastructural analysis also reveals that most immature hair cells had autophagic vacuoles, implying that they originated from damaged hair cells rather than supporting cells. Some transitional cells are supporting cells participating in scar formations. Supporting cells also decrease in number during hair cell recovery, supporting the conclusion that some supporting cells undergo phenotypic conversion into hair cells without an intervening mitotic event.

Non-NASA Center↗
NASA NTRS2013

mBAND Analysis of Early and Late Damages in the Chromosome of Human Lymphocytes after Exposures to Gamma Rays and Fe Ions

Stable type chromosome aberrations that survive multiple generations of cell division include translocation and inversions. An efficient method to detect an inversion is multi-color banding fluorescent in situ hybridization (mBAND) which allows identification of both inter- and intrachromosome aberrations simultaneously. Post irradiation, chromosome aberrations may also arise after multiple cell divisions as a result of genomic instability. To investigate the stable or late-arising chromosome aberrations induced after radiation exposure, we exposed human lymphocytes to gamma rays and Fe ions ex vivo, and cultured the cells for multiple generations. Chromosome aberrations were analyzed in cells collected at first mitosis and at several time intervals during the culture period post irradiation. With gamma irradiation, about half of the damages observed at first mitosis remained after 7 day- and 14 day- culture, suggesting the transmissibility of damages to the surviving progeny. At the doses that produced similar frequencies of gamma-induced chromosome aberrations as observed at first mitosis, a significantly lower yield of aberrations remained at the same population doublings after Fe ion exposure. At these equitoxic doses, more complex type aberrations were observed for Fe ions, indicating that Fe ion-induced initial chromosome damages are more severe and may lead to cell death. Detailed analysis of breaks participating in total chromosome exchanges within the first cell cycle post irradiation revealed a common hotspot located in the 3p21 region, which is a known fragile site corresponding to the band 6 in the mBand analysis. The breakpoint distribution in chromosomes collected at 7 days, but not at 14 days, post irradiation appeared similar to the distribution in cells collected within the first cell cycle post irradiation. The breakpoint distribution for human lymphocytes after radiation exposure was different from the previously published distribution for human mammary epithelial cells, indicating that interphase chromatin folding structures play a role in the distribution of radiation-induced breaks.

Sunagawa, Mayumi↗
NASA NTRS2003

Interactions between neutrophils and macrophages promote macrophage killing of rat muscle cells in vitro

Current evidence indicates that the physiological functions of inflammatory cells are highly sensitive to their microenvironment, which is partially determined by the inflammatory cells and their potential targets. In the present investigation, interactions between neutrophils, macrophages and muscle cells that may influence muscle cell death are examined. Findings show that in the absence of macrophages, neutrophils kill muscle cells in vitro by superoxide-dependent mechanisms, and that low concentrations of nitric oxide (NO) protect against neutrophil-mediated killing. In the absence of neutrophils, macrophages kill muscle cells through a NO-dependent mechanism, and the presence of target muscle cells causes a three-fold increase in NO production by macrophages, with no change in the concentration of inducible nitric oxide synthase. Muscle cells that are co-cultured with both neutrophils and macrophages in proportions that are observed in injured muscle show cytotoxicity through a NO-dependent, superoxide-independent mechanism. Furthermore, the concentration of myeloid cells that is necessary for muscle killing is greatly reduced in assays that use mixed myeloid cell populations, rather than uniform populations of neutrophils or macrophages. These findings collectively show that the magnitude and mechanism of muscle cell killing by myeloid cells are modified by interactions between muscle cells and neutrophils, between muscle cells and macrophages and between macrophages and neutrophils.

Non-NASA Center↗
NASA NTRS1971

Study of the Effects of Ultrasonic Waves on the Reproductive Integrity of Mammalian Cells Cultured in Vitro

The effects of monochromatic ultrasonic waves of 0.1, 0.5, 1.0, 2.0 and, 3.3 MHz frequency on the colony-forming ability of mammalian cells (M3-1,V79, Chang's and T-1) cultured in vitro have been studied to determine the nature of the action of ultrasonic energy on biological systems at the cellular level. The combined effect of ultrasound and X-rays has also been studied. It is concluded: (1) Ultrasonic irradiation causes both lethal and sublethal damage. (2) There is a threshold dose rate for lethal effects. (3) The effectiveness of ultrasonic waves in causing cell death probably depends on the frequency and the amplitude of the waves for a given cell line, indicating a possible resonance phenomenon.

Martins, B. I.↗
NASA NTRS2004

Allograft tolerance induced by donor apoptotic lymphocytes requires phagocytosis in the recipient

Cell death through apoptosis plays a critical role in regulating cellular homeostasis. Whether the disposal of apoptotic cells through phagocytosis can actively induce immune tolerance in vivo, however, remains controversial. Here, we report in a rat model that without using immunosuppressants, transfusion of apoptotic splenocytes from the donor strain prior to transplant dramatically prolonged survival of heart allografts. Histological analysis verified that rejection signs were significantly ameliorated. Splenocytes from rats transfused with donor apoptotic cells showed a dramatically decreased response to donor lymphocyte stimulation. Most importantly, blockade of phagocytosis in vivo, either with gadolinium chloride to disrupt phagocyte function or with annexin V to block binding of exposed phosphotidylserine to its receptor on phagocytes, abolished the beneficial effect of transfused apoptotic cells on heart allograft survival. Our results demonstrate that donor apoptotic cells promote specific allograft acceptance and that phagocytosis of apoptotic cells in vivo plays a crucial role in maintaining immune tolerance.

NASA Discipline Regulatory Physiology↗
NASA NTRS2011

Microgravity-Enhanced Stem Cell Selection

Stem cells, both embryonic and adult, promise to revolutionize the practice of medicine in the future. In order to realize this potential, a number of hurdles must be overcome. Most importantly, the signaling mechanisms necessary to control the differentiation of stem cells into tissues of interest remain to be elucidated, and much of the present research on stem cells is focused on this goal. Nevertheless, it will also be essential to achieve large-scale expansion and, in many cases, assemble cells in 3D as transplantable tissues. To this end, microgravity analog bioreactors can play a significant role. Microgravity bioreactors were originally conceived as a tool to study the cellular responses to microgravity. However, the technology can address some of the shortcomings of conventional cell culture systems; namely, the deficiency of mass transport in static culture and high mechanical shear forces in stirred systems. Unexpectedly, the conditions created in the vessel were ideal for 3D cell culture. Recently, investigators have demonstrated the capability of the microgravity bioreactors to expand hematopoietic stem cells compared to static culture, and facilitate the differentiation of umbilical cord stem cells into 3D liver aggregates. Stem cells are capable of differentiating into functional cells. However, there are no reliable methods to induce the stem cells to form specific cells or to gain enough cells for transplantation, which limits their application in clinical therapy. The aim of this study is to select the best experimental setup to reach high proliferation levels by culturing these cells in a microgravity-based bioreactor. In typical cell culture, the cells sediment to the bottom surface of their container and propagate as a one-cell-layer sheet. Prevention of such sedimentation affords the freedom for self-assembly and the propagation of 3D tissue arrays. Suspension of cells is easily achievable using stirred technologies. Unfortunately, in conventional bioreactors, stirring invokes deleterious forces that disrupt cell aggregation and results in cell death. First-generation rotating bioreactors provided rotation on the horizontal axis, which resulted in the suspension of cells without stirring, thus providing a suitable environment to propagate cells without sedimentation to a surface. The rotating wall bioreactors did not provide a way to remove air bubbles that were causing shear and disrupting 3D cultures. Johnson Space Center successfully engineered the hydrofocusing bioreactor (HFB) that resolved the problem of removing the air bubbles from the fluid medium of NASA's rotating-wall space bioreactors. The HFB uses the principle of hydrodynamic focusing that simultaneously produces a low-shear fluid culture environment and a variable hydrofocusing force that can control the movement, location, and removal of suspended cells, tissues, and air bubbles from the bioreactor. The HFB is a rotating, domeshaped cell culture vessel with a centrally located sampling port and an internal viscous spinner. The vessel and spinner can rotate at different speeds either in the same or opposite directions. Rotation of the vessel and viscous interaction at the spinner generate a hydrofocusing force. Adjusting the differential rotation rate between vessel and spinner controls the magnitude of the force.

Claudio, Pier Paolo↗
DOE OSTI2025

Automated Label‐Free Assay for Viral Detection and Inhibitor Screening via Biomembrane‐Functionalized Microelectrode Arrays

Most virus infection assays have indirect readout such as virus number following entry (e.g., PCR, cell lysis). While effective, these technologies are labor‐intensive, require specialized environments (e.g., sterile or RNA‐free), and detect later‐stage viral events like lysis or cell death, lacking sensitivity to early fusion events. To address these limitations, we present biologically relevant 2D membrane materials, host‐cell‐derived supported lipid bilayers (hcd‐SLBs), integrated with organic microelectrode arrays (OMEAs) for detection of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) fusion. By overexpressing angiotensin‐converting enzyme 2 (ACE2) receptors on the native membranes, the platform functions as a viral sensor capable of detecting virus pseudo particles (VPPs) through the late pathway. Additionally, hcd‐SLBs extracted from human lung epithelium expressing native ACE2 detect fusion events through the early pathway. The platform's utility as a drug‐screening tool is demonstrated by testing antibodies targeting either the ACE2 on the host membrane or the viral spike (S) proteins. To enhance the throughput, microfluidics are integrated for automation and OMEAs are incorporated within each channel, miniaturizing the testing units. This system supports high‐throughput data generation, automation, and scalability, providing an efficient platform for viral fusion detection that advances the study of pathogen‐host interactions and accelerates antiviral drug discovery.

Biology↗
NASA NTRS2016

Translational Cellular Research on the International Space Station

The emerging field of Translational Research aims to coalesce interdisciplinary findings from basic science for biomedical applications. To complement spaceflight research using human subjects, translational studies can be designed to address aspects of space-related human health risks and help develop countermeasures to prevent or mitigate them, with therapeutical benefits for analogous conditions experienced on Earth. Translational research with cells and model organisms is being conducted onboard the International Space Station (ISS) in connection with various human systems impacted by spaceflight, such as the cardiovascular, musculoskeletal, and immune systems. Examples of recent cell-based translational investigations on the ISS include the following. The JAXA investigation Cell Mechanosensing seeks to identify gravity sensors in skeletal muscle cells to develop muscle atrophy countermeasures by analyzing tension fluctuations in the plasma membrane, which changes the expression of key proteins and genes. Earth applications of this study include therapeutic approaches for some forms of muscular dystrophy, which appear to parallel aspects of muscle wasting in space. Spheroids is an ESA investigation examining the system of endothelial cells lining the inner surface of all blood vessels in terms of vessel formation, cellular proliferation, and programmed cell death, because injury to the endothelium has been implicated as underpinning various cardiovascular and musculoskeletal problems arising during spaceflight. Since endothelial cells are involved in the functional integrity of the vascular wall, this research has applications to Earth diseases such as atherosclerosis, diabetes, and hypertension. The goal of the T-Cell Activation in Aging NASA investigation is to understand human immune system depression in microgravity by identifying gene expression patterns of candidate molecular regulators, which will provide further insight into factors that may play a critical role in immune function loss during aging. In addition, Omics investigations with cells have synergistic applications ranging from the evaluation of pharmacological countermeasures to drug discovery. Thus, cell-based translational research onboard the ISS is bidirectionally bridging cutting-edge cellular and molecular approaches with space bioastronautics and human health methodologies on Earth.

Love, John↗