Search NASA⌕ Search

SEARCH · Search NASA

Results for “Signal Transduction”

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 127 records · Page 7
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

DNA parts and gene constructs for plant biodesign

Plant biodesign requires the knowledge of DNA parts (e.g., genes, promoters, terminators), along with their combinations (as gene constructs) linked to engineered traits. DNA parts with validated or predicted functions in plants have been deposited in various online databases. However, these existing databases focus on basic biological functions of individual DNA parts, leaving a gap between basic knowledge and bioengineering applications. To fill this knowledge gap, we have created a user-friendly, open-ended database as a knowledge graph linking DNA parts to gene constructs to traits. This database contains experimentally validated DNA parts and gene constructs documented in peer-reviewed publications. The DNA parts include 1) molecular components with biological functions, such as genes involved in various biological processes (e.g., metabolic and signal transduction pathways) and 2) molecular components with technical functions, such as gene expression, genome engineering and sequence splicing. The gene constructs deposited in this database include both single-gene and multi-gene constructs. This database allows users to submit DNA parts and gene construct compositions linked to engineered traits described in peer-reviewed publications, providing a public digital repository for sharing the biodesign information among the researchers in the fields of plant biotechnology and plant synthetic biology.

plant biodesign synthetic biology gene constructs ↗
DOE OSTI2024

Library Screening, In Vivo Confirmation, and Structural and Bioinformatic Analysis of Pentapeptide Sequences as Substrates for Protein Farnesyltransferase

Protein farnesylation is a post-translational modification where a 15-carbon farnesyl isoprenoid is appended to the C-terminal end of a protein by farnesyltransferase (FTase). This process often causes proteins to associate with the membrane and participate in signal transduction pathways. The most common substrates of FTase are proteins that have C-terminal tetrapeptide CaaX box sequences where the cysteine is the site of modification. However, recent work has shown that five amino acid sequences can also be recognized, including the pentapeptides CMIIM and CSLMQ. In this work, peptide libraries were initially used to systematically vary the residues in those two parental sequences using an assay based on Matrix Assisted Laser Desorption Ionization–Mass Spectrometry (MALDI-MS). In addition, 192 pentapeptide sequences from the human proteome were screened using that assay to discover additional extended CaaaX-box motifs. Selected hits from that screening effort were rescreened using an in vivo yeast reporter protein assay. The X-ray crystal structure of CMIIM bound to FTase was also solved, showing that the C-terminal tripeptide of that sequence interacted with the enzyme in a similar manner as the C-terminal tripeptide of CVVM, suggesting that the tripeptide comprises a common structural element for substrate recognition in both tetrapeptide and pentapeptide sequences. Molecular dynamics simulation of CMIIM bound to FTase further shed light on the molecular interactions involved, showing that a putative catalytically competent Zn(II)-thiolate species was able to form. Bioinformatic predictions of tetrapeptide (CaaX-box) reactivity correlated well with the reactivity of pentapeptides obtained from in vivo analysis, reinforcing the importance of the C-terminal tripeptide motif. This analysis provides a structural framework for understanding the reactivity of extended CaaaX-box motifs and a method that may be useful for predicting the reactivity of additional FTase substrates bearing CaaaX-box sequences.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Glancing Angle Deposition in Gas Sensing: Bridging Morphological Innovations and Sensor Performances

Glancing Angle Deposition (GLAD) has emerged as a versatile and powerful nanofabrication technique for developing next-generation gas sensors by enabling precise control over nanostructure geometry, porosity, and material composition. Through dynamic substrate tilting and rotation, GLAD facilitates the fabrication of highly porous, anisotropic nanostructures, such as aligned, tilted, zigzag, helical, and multilayered nanorods, with tunable surface area and diffusion pathways optimized for gas detection. This review provides a comprehensive synthesis of recent advances in GLAD-based gas sensor design, focusing on how structural engineering and material integration converge to enhance sensor performance. Key materials strategies include the construction of heterojunctions and core–shell architectures, controlled doping, and nanoparticle decoration using noble metals or metal oxides to amplify charge transfer, catalytic activity, and redox responsiveness. GLAD-fabricated nanostructures have been effectively deployed across multiple gas sensing modalities, including resistive, capacitive, piezoelectric, and optical platforms, where their high aspect ratios, tailored porosity, and defect-rich surfaces facilitate enhanced gas adsorption kinetics and efficient signal transduction. These devices exhibit high sensitivity and selectivity toward a range of analytes, including NO2, CO, H2S, and volatile organic compounds (VOCs), with detection limits often reaching the parts-per-billion level. Emerging innovations, such as photo-assisted sensing and integration with artificial intelligence for data analysis and pattern recognition, further extend the capabilities of GLAD-based systems for multifunctional, real-time, and adaptive sensing. Finally, current challenges and future research directions are discussed, emphasizing the promise of GLAD as a scalable platform for next-generation gas sensing technologies.

Chemistry↗
DOE OSTI2025

Plant Defense Proteins: Recent Discoveries and Applications

Proteins play pivotal roles in safeguarding plants against numerous biotic and abiotic stresses. Understanding their biological functions and mechanisms of action is essential for advancing plant biology, agriculture, and biotechnology. This review considers the diversity and potential applications of plant defense proteins including pathogenesis-related (PR) proteins, chitinases, glucanases, protease inhibitors, lectins, and antimicrobial peptides. Recent advances, such as the omics technologies, have enabled the discovery of new plant defense proteins and regulatory networks that govern plant defense responses and unveiled numerous roles of plant defense proteins in stress perception, signal transduction, and immune priming. The molecular affinities and enzymatic activities of plant defense proteins are essential for their defense functions. Applications of plant defense proteins span agriculture, biotechnology, and medicine, including the development of resistant crop varieties, bio-based products, biopharmaceuticals, and functional foods. Future research directions include elucidating the structural bases of defense protein functions, exploring protein interactions with ligands and other proteins, and engineering defense proteins for enhanced efficacy. Overall, this review illuminates the significance of plant defense proteins against biotic stresses in plant biology and biotechnology, emphasizing their potential for sustainable agriculture and environmental management.

G-proteins↗
NASA NTRS1984

Mechanism of colour discrimination by a bacterial sensory rhodopsin

A photosensitive protein resembling the visual pigments of invertebrates enables phototactic archaebacteria to distinguish color. This protein exists in two spectrally-distinct forms, one of which is a transient photoproduct of the other and each of which undergoes photochemical reactions controlling the cell's swimming behaviour. Activation of a single pigment molecule in the cell is sufficient to signal the flagellar motor. This signal-transduction mechanism makes evident a color-sensing capability inherent in the retinal/protein chromophore.

Spudich, J. L.↗
NASA NTRS1990

Rapid increase of inositol 1,4,5-trisphosphate in the HeLa cells after hypergravity exposure

The IP3 level in HeLa cells has been elevated through the application in hypergravity in a time-dependent manner. The data obtained for the hydrolytic products of PIP2, IP3, and DG are noted to modulate c-myc gene expression. It is also established that the cAMP accumulation by the IBMX in hypergravity-exposed cells was suppressed relative to the control. In light of IP3 increase and cAMP decrease results, a single GTP-binding protein may play a role in the hypergravity signal transduction of HeLa cells by stimulating PLC while inhibiting adenylate cyclase.

Kumei, Yasuhiro↗
NASA NTRS1992

Clinostats and Centrifuges: Their Use, Value, and Limitations in Gravitational Biological Research

The present volume addresses physical phenomena and effects associated with clinostat and centrifuge operations as well as their physiological effects. Particular attention is given to the simulation of the gravity conditions on the ground, the internal dynamics of slowly rotating biological systems, and qualitative and quantitative aspects of the fast-rotating clinostat as a research tool. Also discussed are the development and use of centrifuges in gravitational biology, the use of centrifuges in plant gravitational biology and a comparison of ground-based and flight experiment results, the ability of clinostat to mimic the effect of microgravity on plant cells and organs, and the impact of altered gravity conditions on early EGF-induced signal transduction in human epidermal A431 cells.

Halstead, Thora W.↗
NASA NTRS1996

Calcium-Dependent Protein Kinase Genes in Corn Roots

Two cDNAs encoding Ca-2(+) - Dependent Protein Kinases (CDPKs), Corn Root Protein Kinase 1 and 2 (CRPK 1, CRPK 2) were isolated from the root tip library of corn (Zea mays L., cv. Merit) and their nucleotide sequences were determined. Deduced amino acid sequences of both the clones have features characteristic of plant CDPKS, including all 11 conserved serine/threonine kinase subdomains, a junction domain and a calmodulin-like domain with four Ca-2(+), -binding sites. Northern analysis revealed that CRPKI mRNA is preferentially expressed in roots, especially in the root tip; whereas, the expression of CRPK2 mRNA was very low in all the tissues tested. In situ hybridization experiments revealed that CRPKI mRNA is highly expressed in the root apex, as compared to other parts of the root. Partially purified CDPK from the root tip phosphorylates syntide-2, a common peptide substrate for plant CDPKs, and the phosphorylation was stimulated 7-fold by the addition of Ca-2(+). Our results show that two CDPK isoforms are expressed in corn roots and they may be involved in the Ca-2(+)-dependent signal transduction process.

Takezawa, D.↗
NASA NTRS1997

A Method for Preparation, Storage and Activation of Large Populations of Immotile Sea Urchin Sperm

Reversible protein phosphorylation is associated with initiation and modulation of sperm flagellar motility. Many studies aimed at examining the signal transduction mechanisms underlying the expression of motility have relied on detergent-permeabilized sperm reactivated with exogenous 32 P-ATP. However, the reactivation conditions allow variable levels of motility to be expressed and phosphorylation of many proteins that appear to be unrelated to sperm motility. Thus, identification of the few relevant proteins is difficult. We have developed a method to collect and keep sperm immotile until reactivated for analysis to normal motility levels. Artificial sea water (ASW) buffered with 5 mM 2-[N-morpholino]ethanesulfonic acid at pH 6.0 and containing 50 mM KCI, allows collection and storage of immotile sea urchin sperm for up to 96 h at 4-5 C. Motility under these conditions is essentially zero, but sperm is rapidly reactivated to normal motility by diluting with ASW to standard pH (8.0) and KCI concentration (10 mM).

Bracho, Geracimo E.↗
NASA NTRS1999

The Effects of Orbital Spaceflight on Human Osteoblastic Cell Physiology and Gene Expression

The purpose of the proposed study is to establish whether changes in gravitational loading have a direct effect on osteoblasts to regulate TGF-6 expression. The effects of spaceflight and reloading on TGF-B MRNA and peptide levels will be studied in a newly developed line of immortalized human fetal osteoblasts (HFOB) transfected with an SV-40 temperature dependent mutant to generate proliferating, undifferentiated hFOB cells at 33-34 C and a non-proliferating, differentiated HFOB cells at 37-39'C. Unlike previous cell culture models, HFOB cells have unlimited proliferative capacity yet can be precisely regulated to differentiate into mature cells which express mature osteoblast function. If isolated osteoblasts respond to changes in mechanical loading in a manner similar to their response in animals, the cell system could provide a powerful model to investigate the signal transduction pathway for gravitational loading.

Turner, R. T.↗
NASA NTRS1999

Bone Blood Flow During Simulated Microgravity: Physiological and Molecular Mechanisms

Blood flow to bone has been shown to affect bone mass and presumably bone strength. Preliminary data indicate that blood flow to the rat femur decreases after 14 days of simulated microgravity, using hindlimb suspension (HLS). If adult rats subjected to HLS are given dobutamine, a synthetic catecholamine which can cause peripheral vasodilation and increased blood flow, the loss of cortical bone area usually observed is prevented. Further, mechanisms exist at the molecular level to link changes in bone blood flow to changes in bone cell activity, particularly for vasoactive agents like nitric oxide (NO). The decreases in fluid shear stress created by fluid flow associated with the shifts of plasma volume during microgravity may result in alterations in expression of vasoactive agents such as NO, producing important functional effects on bone cells. The primary aim of this project is to characterize changes in 1) bone blood flow, 2) indices of bone mass, geometry, and strength, and 3) changes in gene expression for modulators of nitric oxide activity (e.g., nitric oxide synthase) and other candidate genes involved in signal transduction of mechanical loading after 3, 7, 14, 21, and 28 days of HLS in the adult rat. Using a rat of at least 5 months of age avoids inadvertently studying effects of simulated microgravity on growing, rather than adult, bone. Utilizing the results of these studies, we will then define how altered blood flow contributes to changes in bone with simulated microgravity by administering a vasodilatory agent (which increases blood flow to tissues) during hindlimb suspension. In all studies, responses in the unloaded hindlimb bones (tibial shaft, femoral neck) will be compared with those in the weightbearing humeral shaft and the non-weightbearing calvarium (skull) from the same animal. Bone volumetric mineral density and geometry will be quantified by peripheral quantitative CT; structural and material properties of the long bones will be determined by 3-point bending (tibia, humerus) or compression (femoral neck) testing to failure. A unique aspect of these studies will be defining the time course of changes in gene expression in bone cell populations with unloading, accomplished with Northern blots, in situ hybridization, and immunohistochemistry. These studies have high relevance for concurrent protocols being proposed by investigators on NSBRI Cardiovascular and Muscle teams, with blood flow data available on a number of tissues other than bone. Further, dobutamine and other Beta-agonists have been tested as countermeasures for altered muscle and cardiovascular function. Results of the intervention tested in our studies have potential relevance for a number of systemic changes seen with prolonged spaceflight.

Bloomfield, Susan A.↗
NASA NTRS1998

Protein Kinases Possibly Mediate Hypergravity-Induced Changes in F-Actin Expression by Endothelial Cells

Basic cellular functions such as electrolyte concentration, cell growth rate, glucose utilization, bone formation, response to growth stimulation, and exocytosis are modified in microgravity. These studies indicate that microgravity affects a number of physiological systems and included in this are cell signaling mechanisms. Rijken and coworkers performed growth factor studies that showed PKC signaling and actin microfilament organization appears to be sensitive to microgravity, suggesting that the inhibition of signal transduction by microgravity may be related to alterations in actin microfilament organization. However, similar studies have not been done for vascular cells. Vascular endothelial cells play critical roles in providing nutrients to organ and tissues and in wound repair. The major deterrent to ground-based microgravity studies is that it is impossible to achieved true microgravity for longer than a few minutes on earth. Hence, it has not been possible to conduct prolonged microgravity studies except for two models that simulate certain aspects of microgravity. However, hypergravity is quite easily achieved. Several researchers have shown that hypergravity will increase the proliferation of several different cell lines while decreasing cell motility and slowing liver regeneration following partial hepatectomy, These studies indicate the hypergravity also alters the behavior of most cells. Several investigators have shown that hypergravity affects the activation of several protein kinases (PKs) in cells. In this study, we investigated whether hypergravity alters the expression of f-actin by bovine aortic endothelial cells (BAECs) and the role of PK's (calmodulin 11 dependent, PKA and PKC) as mediators of these effects.

Love, Felisha D.↗
NASA NTRS1999

On The Development of Biophysical Models for Space Radiation Risk Assessment

Experimental techniques in molecular biology are being applied to study biological risks from space radiation. The use of molecular assays presents a challenge to biophysical models which in the past have relied on descriptions of energy deposition and phenomenological treatments of repair. We describe a biochemical kinetics model of cell cycle control and DNA damage response proteins in order to model cellular responses to radiation exposures. Using models of cyclin-cdk, pRB, E2F's, p53, and GI inhibitors we show that simulations of cell cycle populations and GI arrest can be described by our biochemical approach. We consider radiation damaged DNA as a substrate for signal transduction processes and consider a dose and dose-rate reduction effectiveness factor (DDREF) for protein expression.

Cucinotta, F. A.↗
NASA NTRS2000

T Lymphocyte Activation Threshold is Increased in Reduced Gravity

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

Adams, Charley L.↗
NASA NTRS1999

T Cell Activation Thresholds are Affected by Gravitational

T cells stimulated in space flight by various mitogenic signals show a dramatic reduction in proliferation and expression of early activation markers. Similar results are also obtained in a ground based model of microgravity, clinorotation, which provides a vector-averaged reduction of the apparent gravity on cells without significant shear force. Here we demonstrate that T cell inhibition is due to an increase in the required threshold for activation. Dose response curves indicate that cells activated during clinorotation require higher stimulation to achieve the same level of activation, as measured by CD69 expression. Interleukin 2 receptor expression, and DNA synthesis. The amount of stimulation necessary for 50% activation is 5 fold in the clinostat relative to static. Correlation of TCR internalization with activation also exhibit a dramatic right shift in clinorotation, demonstrating unequivocally that signal transduction mechanism independent of TCR triggering account for the increased activation threshold. Previous results from space flight experiments are consistent with the dose response curves obtained for clinorotation. Activation thresholds are important aspects of T cell memory, autoimmunity and tolerance Clinorotation is a useful, noninvasive tool for the study of cellular and biochemical event regulating T cell activation threshold and the effects of gravitation forces on these systems.

Adams, Charley↗
NASA NTRS1999

PKC Isoform Expression in Modeled Microgravity

Our previous studies showed that modeled (MMG) and true (USA Space Shuttle Missions STS-54 and STS-56) microgravity (MG) inhibit human lymphocyte locomotion, Modeled MG also suppressed polyclonal and antigen-specific lymphocyte activation. Activation of PKC by phorbol myristate acetate (PMA) restored the microgravity-inhibited lymphocyte locomotion as well as activation by phytohaemagglutinin (PHA), whereas calcium ionophore (ionomycin) was unable to restore these functions. Based on these results we hypothesized that MG-induced changes in lymphocyte functions are caused by a fundamental defect in signal transduction mechanism. This defect may be localized either at the PKC level or upstream of PKC, most likely, at the cell membrane level. In this study we examined the expression of PKC isoforms alpha, epsilon and delta in PBMC cultured in rotating wall vessel bioreactor, developed at NASA JSC, which models microgravity by sustaining cells in continuous free fall. The assessment of the isoforms was performed by FACS analysis following cell permeabilization. A decrease in the expression of isoforms epsilon and delta, but not isoform a, was observed in PBMC cultured in microgravity conditions. These data suggest that MMG might selectively affect the expression of Ca2+ independent isoforms of PKC Molecular analysis confirm selective suppression of Ca2+ independent isoforms of PKC.

Risin, Diana↗
NASA NTRS2003

Radiation Dose-effects on Cell Cycle, Apoptosis, and Marker Expression of Ataxia Telangiectasia-Heterozygous Human Breast Epithelial Cells

Ataxia-telangiectasia (A-T) is a radiation-sensitive genetic condition. AT-heterozygous human mammary epithelial cells (HMEC) were irradiated using a Cs137 source in order to compare cell cycle, apoptosis, and marker expression responses across 3 radiation doses. No differences in cell cycle and apoptosis were found with any of the radiation doses used (30, 60, and 90 rads) compared with the unirradiated control (0 rad). At the same doses, however, differences were found in marker expression, such as keratin 18 (kl8), keratin 14 (k14), insulin-like growth factor I receptor (IGF-IR), and connexin 43 (cx43). This may indicate that radiation sensitivity in the heterozygous state may be initiated through signal transduction responses.

Cruz, A.↗
NASA NTRS2004

Structural Basis for the Catalytic Activity of Human Serine/Threonine Protein Phosphatase type 5 (PP5)

Serine/threonine protein phosphatase-5 (PP5) is a member of the PPP-gene family of protein phosphatases that is widely expressed in mammalian tissues and is highly conserved among eukaryotes. PP5 associates with several proteins that affect signal transduction networks, including the glucocorticoid receptor (GR)-heat shock protein-90 (Hsp90)-heterocomplex, the CDC16 and CDC27 subunits of the anaphase-promoting complex, elF2alpha kinase, the A subunit of PP2A, the G12-alpha / G13-alpha subunits of heterotrimeric G proteins and DNA-PK. The catalytic domain of PP5 (PP5c) shares 35-45% sequence identity with the catalytic domains of other PPP-phosphatases, including protein phosphatase-1 (PP1), -2A (PP2A), -2B / calcineurin (PP2B), -4 (PP4), -6 (PP6), and -7 (PP7). Like PP1, PP2A and PP4, PP5 is also sensitive to inhibition by okadaic acid, microcystin, cantharidin, tautomycin, and calyculin A. Here we report the crystal structure of the PP5 catalytic domain (PP5c) at a resolution of 1.6 angstroms. From this structure we propose a mechanism for PP5-mediated hydrolysis of phosphoprotein substrates, which requires the precise positioning of two metal ions within a conserved Asp(sup 271)-M(sub 1):M(sub 2)-W(sup 1)-His(sup 304)-Asp(sup 274) catalytic motif. The structure of PP5c provides a possible structural basis for explaining the exceptional catalytic proficiency of protein phosphatases, which are among the most powerful known catalysts. Resolution of the entire C-terminus revealed a novel subdomain, and the structure of the PP5c should also aid development of type-specific inhibitors.

Swingle, Mark R.↗