Search NASA⌕ Search

SEARCH · Search NASA

Results for “Synthetic Biology”

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 73 records · Page 4

An argument for using anaerobes as microbial cell factories to advance synthetic biology and biomanufacturing

Anaerobes thrive in the absence of oxygen and are an untapped reservoir of biotechnological potential. Therefore, bioprospecting efforts focused on anaerobic microbial diversity could rapidly uncover new enzymes, pathways, and chassis organisms to drive biotechnology innovation. Despite their potential utility, anaerobic fermenters are viewed as inefficient from a biochemical perspective because their metabolisms produce fewer ATP (~2) per molecule of glucose processed than heterotrophic respirers (~32–38 ATP). While aerobes excel at ATP generation, they are often less efficient than anaerobes at processes that compete with ATP generation for cellular resources. This perspective highlights how anaerobic adaptations are advantageous for synthetic biology and biomanufacturing applications through the engineering of microbial cell factories. We further highlight emerging applications of anaerobic bioprocessing, including the use of anaerobic metabolisms for lignocellulosic bioprocessing, human and environmental health, and value-added bioproduction.

59 BASIC BIOLOGICAL SCIENCES↗

Materials Manufactured from 3D Printed Synthetic Biology Arrays

Many complex, biologically-derived materials have extremely useful properties (think wood or silk), but are unsuitable for space-related applications due to production, manufacturing, or processing limitations. Large-scale ecosystem-based production, such as raising and harvesting trees for wood, is impractical in a self-contained habitat such as a space station or potential Mars colony. Manufacturing requirements, such as the specialized equipment needed to harvest and process cotton, add too much upmass for current launch technology. Cells in nature are already highly specialized for making complex biological materials on a micro scale. We envision combining these strengths with the recently emergent technologies of synthetic biology and 3D printing to create 3D-structured arrays of cells that are bioengineered to secrete different materials in a specified three-dimensional pattern.

Gentry, Diana↗

Plant synthetic biology innovations for biofuels and bioproducts

Plant-based biosynthesis of fuels, chemicals, and materials promotes environmental sustainability, which includes decreases in greenhouse gas emissions, water pollution, and loss of biodiversity. Advances in plant synthetic biology (synbio) should improve precision and efficacy of genetic engineering for sustainability. Applicable synbio innovations include genome editing, gene circuit design, synthetic promoter development, gene stacking technologies, and the design of environmental sensors. Moreover, recent advancements in developing spatially resolved and single-cell omics contribute to the discovery and characterization of cell-type-specific mechanisms and spatiotemporal gene regulations in distinct plant tissues for the expression of cell- and tissue-specific genes, resulting in improved bioproduction. In conclusion, this review highlights recent plant synbio progress and new single-cell molecular profiling towards sustainable biofuel and biomaterial production.

Yang, Yongil↗

Microbial Extremophiles for Earth and Beyond: Pushing the Boundaries with Synthetic Biology

All organisms live in a multi-dimensional physical and chemical niche space. Discoveries in the 20th century enormously expanded the range of what was considered "habitable." However, the current diversity of life on Earth begs the question of what terrestrial life - or indeed, another life form - would be capable of. With the needs of both modern laboratory science and the burgeoning field of biotechnology, as well as our deeply held desire to answer the question "are we alone in the universe?, we are exploiting the tools of synthetic biology to probe the question of whether we can create "synthetic extremophiles" or, as our lab has dubbed them, "Hell Cells."

synthetic extremophiles↗

On Beyond Star Trek: Synthetic Biology and the Future of Space Exploration

A turtle carries its own habitat. While it is reliable, it costs energy. NASA makes the same trade-off when it transports habitats and other structures needed to lunar and planetary surfaces increasing upmass, and affecting other mission goals. Long-term human space presence requires periodic replenishment, adding a massive cost overhead. Even robotic missions often sacrifice science goals for heavy radiation and thermal protection. Biology has the potential to solve these problems because it can replicate and repair itself, and do a wide variety of chemical reactions including making food, fuel and materials. Synthetic biology enhances and expands life's evolved repertoire. Using organisms as feedstock, additive manufacturing could make possible the dream of producing bespoke tools, food, smart fabrics and even replacement organs on demand. Imagine what new products can be enabled by such a technology, on earth or beyond!

Rothschild, Lynn J.↗

Leveraging a synthetic biology approach to enhance BCG-mediated expansion of Vγ9Vδ2 T cells

There is an urgent need to develop a more efficacious anti-tuberculosis vaccine as the current live-attenuated vaccine strain BCG fails to prevent pulmonary infection in adults. In this study, we leverage a synthetic biology approach to engineer BCG to produce more (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), an intermediate of bacterial—but not host—isoprenoid biosynthesis via the methylerythritol phosphate (MEP) pathway. HMBPP strongly activates and expands Vγ9Vδ2 T cells, which are unique to higher-order primates and protect against Mycobacterium tuberculosis infection. BCG has been engineered to produce specific ligands and antigens to some success; in contrast, our strategy exploits a self-nonself recognition mechanism in the host via HMBPP sensing, which has not been attempted before. To inform the design of our recombinant strains, we performed synteny analyses of >63 mycobacterial species and found that isoprenoid biosynthetic genes are not operonic across all the 356 surveyed genomes, but some genes are frequently found in pairs. Thus, we generated synthetic loci with the goal of specifically overproducing HMBPP and tested the ability of these engineered strains to induce human Vγ9Vδ2 expansion in an in vitro stimulation assay. We found that BCG expressing a synthetic MEP locus significantly enhanced Vγ9Vδ2 T cell expansion over the wild-type vaccine strain, and overexpression of the HMBPP synthase GcpE alone potently induced Vγ9Vδ2 T cell expansion with no downregulation of other pathway genes. Together these engineered strains present two successful strategies to accumulate HMBPP and overcome feedback inhibition of the MEP pathway.

59 BASIC BIOLOGICAL SCIENCES↗

Testing of Synthetic Biological Membranes for Forward Osmosis Applications

Commercially available forward osmosis membranes have been extensively tested for human space flight wastewater treatment. Despite the improvements achieved in the last decades, there is still a challenge to produce reliable membranes with anti-fouling properties, chemical resistance, and high flux and selectivity. Synthetic biological membranes that mimic the ones present in nature, which underwent millions of years of evolution, represent a potential solution for further development and progress in membrane technology. Biomimetic forward osmosis membranes based on a polymeric support filter and coated with surfactant multilayers have been engineered to investigate how different manufacturing processes impact the performance and structure of the membrane. However, initial results of the first generation prototype membranes tests reveal a high scatter in the data, due to the current testing apparatus set up. The testing apparatus has been upgraded to improve data collection, reduce errors, and to allow higher control of the testing process.

Forward osmosis↗

Synthetic Biology and the Search for Extraterrestrial Life

"Are we alone?" is one of the primary questions of astrobiology, and whose answer defines our significance in the universe. Unfortunately, this quest is hindered by the fact that we have only one confirmed example of life, that of earth. While this is enormously helpful in helping to define the minimum envelope for life, it strains credulity to imagine that life, if it arose multiple times, has not taken other routes. To help fill this gap, our lab has begun using synthetic biology - the design and construction of new biological parts and systems and the redesign of existing ones for useful purposes - as an enabling technology. One theme, the "Hell Cell" project, focuses on creating artificial extremophiles in order to push the limits for Earth life, and to understand how difficult it is for life to evolve into extreme niches. In another project, we are re-evolving biotic functions using only the most thermodynamically stable amino acids in order to understand potential capabilities of an early organism with a limited repertoire of amino acids.

amino acids↗

Synthetic Biology and the Search for Extraterrestrial Life

"Are we alone?" is one of the primary questions of astrobiology, and whose answer defines our significance in the universe. Unfortunately, this quest is hindered by the fact that we have only one confirmed example of life, that of earth. While this is enormously helpful in helping to define the minimum envelope for life, it strains credulity to imagine that life, if it arose multiple times, has not taken other routes. To help fill this gap, our lab has begun using synthetic biology - the design and construction of new biological parts and systems and the redesign of existing ones for useful purposes - as an enabling technology. One theme, the "Hell Cell" project, focuses on creating artificial extremophiles in order to push the limits for Earth life, and to understand how difficult it is for life to evolve into extreme niches. In another project, we are re-evolving biotic functions using only the most thermodynamically stable amino acids in order to understand potential capabilities of an early organism with a limited repertoire of amino acids.

exobiology↗

Synthetic Biology and the Search for Extraterrestrial Life

Are we alone? is one of the primary questions of astrobiology, and whose answer defines our significance in the universe. Unfortunately, this quest is hindered by the fact that we have only one confirmed example of life, that of earth. While this is enormously helpful in helping to define the minimum envelope for life, it strains credulity to imagine that life, if it arose multiple times, has not taken other routes. To help fill this gap, our lab has begun using synthetic biology, the design and construction of new biological parts and systems and the redesign of existing ones for useful purposes, as an enabling technology. One theme, the Hell Cell project, focuses on creating artificial extremophiles in order to push the limits for Earth life, and to understand how difficult it is for life to evolve into extreme niches (http:2012.igem.orgTeam:Stanford-BrownHellCellIntroduction). In another project, we are re-evolving biotic functions using only the most thermodynamically stable amino acids in order to understand potential capabilities of an early organism with a limited repertoire of amino acids. This should lead to a more universal theory of the origin of life based on materials found commonly in meteorites and other pre-biotic settings.

Hell Cell↗

BioWires: Conductive DNA Nanowires in a Computationally-Optimized, Synthetic Biological Platform for Nanoelectronic Fabrication

DNA is an ideal template for a biological nanowire-it has a linear structure several atoms thick; it possesses addressable nucleobase geometry that can be precisely defined; and it is massively scalable into branched networks. Until now, the drawback of DNA as a conducting nanowire been, simply put, its low conductance. To address this deficiency, we extensively characterize a chemical variant of canonical DNA that exploits the affinity of natural cytosine bases for silver ions. We successfully construct chains of single silver ions inside double-stranded DNA, confirm the basic dC-Ag+-dC bond geometry and kinetics, and show length-tunability dependent on mismatch distribution, ion availability and enzyme activity. An analysis of the absorbance spectra of natural DNA and silver-binding, poly-cytosine DNA demonstrates the heightened thermostability of the ion chain and its resistance to aqueous stresses such as precipitation, dialysis and forced reduction. These chemically critical traits lend themselves to an increase in electrical conductivity of over an order of magnitude for 11-base silver-paired duplexes over natural strands when assayed by STM break junction. We further construct and implement a genetic pathway in the E. coli bacterium for the biosynthesis of highly ionizable DNA sequences. Toward future circuits, we construct a model of transcription network architectures to determine the most efficient and robust connectivity for cell-based fabrication, and we perform sequence optimization with a genetic algorithm to identify oligonucleotides robust to changes in the base-pairing energy landscape. We propose that this system will serve as a synthetic biological fabrication platform for more complex DNA nanotechnology and nanoelectronics with applications to deep space and low resource environments.

DNA↗

Wolffia, a minimalist plant and synthetic biology chassis

A highly simplified species for genome engineering would facilitate rational design of a synthetic plant. A candidate species is the aquatic, non-grass monocot wolffia (Wolffia australiana) in the Lemnaceae family. Commonly known as watermeal, wolffia is a rootless ball of several thousand cells the size of a pinhead and the fastest growing plant known on Earth. Its extreme morphological reduction is coupled to transposon-mediated streamlining of its transcriptome, which represents a core set of nonredundant protein coding genes. Despite its body plan and transcriptome being highly specialized for continuous growth, wolffia retains cell types relevant to higher plants. Finally, systems level studies with this species could enable the creation of a defined biological chassis for synthetic plant construction.

59 BASIC BIOLOGICAL SCIENCES↗

Hijacking Translation Initiation for Synthetic Biology

Genetic code expansion (GCE) has revolutionized the field of protein chemistry. Over the past several decades more than 150 different noncanonical amino acids (ncAAs) have been co-translationally installed into proteins within various host organisms. Further, the vast majority of these ncAAs have been incorporated between the start and stop codons within an open reading frame. This requires that the ncAA be able to form a peptide bond at the α-amine, limiting the types of molecules that can be genetically encoded. In contrast, the α-amine of the initiating amino acid is not required for peptide bond formation. Therefore, including the initiator position in GCE allows for co-translational insertion of more diverse molecules that are modified, or completely lacking an α-amine. This review explores various methods which have been used to initiate protein synthesis with diverse molecules both in vitro and in vivo.

59 BASIC BIOLOGICAL SCIENCES↗

Robust Synthetic Biology Toolkit to Advance Carboxysome Study and Redesign

Carboxysomes are polyhedral protein organelles that microorganisms use to facilitate carbon dioxide assimilation. They are composed of a modular protein shell that envelops an enzymatic core mainly composed of physically coupled Rubisco and carbonic anhydrase. While the modular construction principles of carboxysomes make them attractive targets as customizable metabolic platforms, their size and complexity can be a hindrance. In this work, we design and validate a plasmid set, the pXpressome toolkit, in which α-carboxysomes are robustly expressed and remain intact and functional after purification. We tested this toolkit by introducing mutations that influence carboxysome structure and performance. We find that deletion of vertex-capping genes results in formation of larger carboxysomes, while deletion of facet forming genes produces smaller particles, suggesting that adjusting the ratio of these proteins can rationally affect morphology. Through a series of fluorescently labeled constructs, we observe that this toolkit leads to more uniform expression and better cell health than previously published carboxysome expression systems. Overall, the pXpressome toolkit facilitates the study and redesign of carboxysomes with robust performance and improved phenotype uniformity. The pXpressome toolkit will support efforts to remodel carboxysomes for enhanced carbon fixation or serve as a platform for other nanoencapsulation goals.

59 BASIC BIOLOGICAL SCIENCES↗

An Integrated Computer-Aided Design and Manufacturing Workflow for Synthetic Biology

Biological computer-aided design and manufacturing (bioCAD/CAM) tools facilitate the design and build processes of engineering biological systems using iterative design-build-test-learn (DBTL) cycles. In this book chapter, we highlight some of the bioCAD/CAM tools developed and used at the US Department of Energy (DOE) Joint Genome Institute (JGI), Joint BioEnergy Institute (JBEI), and Agile BioFoundry (ABF). We demonstrate the use of these bioCAD/CAM tools on a common workflow for designing and building a multigene pathway in a hierarchical fashion. Additionally, each tool presented in this book chapter is specifically tailored to support one or more specific steps in a workflow, can be integrated with the others into design and build workflows, and can be deployed at academic, government, or commercial entities.

59 BASIC BIOLOGICAL SCIENCES↗