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NASA NTRS2006

A Strategy to Safely Live and Work in the Space Radiation Environment

The goal of the National Aeronautics and Space Agency and the Space Radiation Project is to ensure that astronauts can safely live and work in the space radiation environment. The space radiation environment poses both acute and chronic risks to crew health and safety, but unlike some other aspects of space travel, space radiation exposure has clinically relevant implications for the lifetime of the crew. The term safely means that risks are sufficiently understood such that acceptable limits on mission, post-mission and multi-mission consequences (for example, excess lifetime fatal cancer risk) can be defined. The Space Radiation Project strategy has several elements. The first element is to use a peer-reviewed research program to increase our mechanistic knowledge and genetic capabilities to develop tools for individual risk projection, thereby reducing our dependency on epidemiological data and population-based risk assessment. The second element is to use the NASA Space Radiation Laboratory to provide a ground-based facility to study the understanding of health effects/mechanisms of damage from space radiation exposure and the development and validation of biological models of risk, as well as methods for extrapolation to human risk. The third element is a risk modeling effort that integrates the results from research efforts into models of human risk to reduce uncertainties in predicting risk of carcinogenesis, central nervous system damage, degenerative tissue disease, and acute radiation effects. To understand the biological basis for risk, we must also understand the physical aspects of the crew environment. Thus the fourth element develops computer codes to predict radiation transport properties, evaluate integrated shielding technologies and provide design optimization recommendations for the design of human space systems. Understanding the risks and determining methods to mitigate the risks are keys to a successful radiation protection strategy.

Corbin, Barbara J.↗

NASA NTRS2010

Tuning Parameters in Heuristics by Using Design of Experiments Methods

With the growing complexity of today's large scale problems, it has become more difficult to find optimal solutions by using exact mathematical methods. The need to find near-optimal solutions in an acceptable time frame requires heuristic approaches. In many cases, however, most heuristics have several parameters that need to be "tuned" before they can reach good results. The problem then turns into "finding best parameter setting" for the heuristics to solve the problems efficiently and timely. One-Factor-At-a-Time (OFAT) approach for parameter tuning neglects the interactions between parameters. Design of Experiments (DOE) tools can be instead employed to tune the parameters more effectively. In this paper, we seek the best parameter setting for a Genetic Algorithm (GA) to solve the single machine total weighted tardiness problem in which n jobs must be scheduled on a single machine without preemption, and the objective is to minimize the total weighted tardiness. Benchmark instances for the problem are available in the literature. To fine tune the GA parameters in the most efficient way, we compare multiple DOE models including 2-level (2k ) full factorial design, orthogonal array design, central composite design, D-optimal design and signal-to-noise (SIN) ratios. In each DOE method, a mathematical model is created using regression analysis, and solved to obtain the best parameter setting. After verification runs using the tuned parameter setting, the preliminary results for optimal solutions of multiple instances were found efficiently.

Arin, Arif↗

NASA NTRS2019

A Multi-Omics Approach Demonstrates that Spaceflight Leads to Lipid Accumulation in Mouse Livers

Spaceflight has several detrimental effects on the physiology of astronauts, many of which are recapitulated in rodent models. We analyzed liver transcriptomic and proteomic data from three mouse spaceflight experiments flown aboard the International Space Station (Rodent Research-1 NASA (RR-1 NASA), Rodent Research-1 CASIS (RR-1 CASIS), Rodent Research-3 (RR-3)), and one mouse experiment flown on the Space Shuttle (Commercial Biomedical Testing Module-3 (CBTM-3) aboard STS-135). Despite the differences in genetic background and time of exposure to microgravity it was shown through Oil Red staining and histology that increased lipid accumulation was occurring in the liver of all mice flown in space compared to the ground controls. This led to further pursue the existing GeneLab datasets related to liver omics data from these mice. We were able to discover key conserved pathways across all the mice independent of the flight conditions that were related to increased lipid metabolism, fatty acid metabolism, both lipid and fatty acid processing, lipid catabolic processing, and lipid localization. In addition, key upstream regulators were predicted to be commonly regulated across all conditions which include ESR1, GCG, and NR1I2 being inhibited and INS being activated. Interestingly, estrogen receptor alpha (ESR1) expression has been known to be heavily involved with lipoprotein metabolism. In addition, insulin (INS) is the primary driver for fat metabolism and increased INS has been associated with increased fatty acids in the liver. Through additional proteomic analysis we were able to identify the majority of the key proteins related to lipids for both the RR-1 and RR-3 rodents were being up-regulated in the livers when comparing flight to ground controls. This additional confirmation of the lipid associated activity also showed that the lipid related proteins are heavily involved with lipid metabolism, cholesterol binding, and cholesterol metabolism. Lastly, the analysis also revealed that the circadian clock related pathways in the liver are commonly being increased across all space flight conditions which has also been reported in the literature to potentially cause increased liver damage. The combination of the very strong lipid uptake in the liver and the transcriptomic/proteomic signatures (including the circadian clock pathways) following spaceflight are consistent with early onset of liver disease. Taken together, these data indicate that, activation of lipotoxic pathways could persist during longer duration spaceflight which might result in the development of liver disease

Lipids↗

NASA NTRS1994

Constrained minimization of smooth functions using a genetic algorithm

The use of genetic algorithms for minimization of differentiable functions that are subject to differentiable constraints is considered. A technique is demonstrated for converting the solution of the necessary conditions for a constrained minimum into an unconstrained function minimization. This technique is extended as a global constrained optimization algorithm. The theory is applied to calculating minimum-fuel ascent control settings for an energy state model of an aerospace plane.

Moerder, Daniel D.↗

NASA NTRSDate not supplied

An Open-Science Approach to Address Individual Response to Simulated GCR In Genetically Diverse Populations of Mice and Humans

This project addresses the challenge of understanding and predicting individual radiation sensitivity by integrating genetics, demographics and biomarker characteristics across species (mice and humans). We hypothesize that ex vivo DNA repair response to GCR components is a central determinant of cancer risk from space radiation and can serve as a biomarker of radiation risk in combination with genetics. Automated image quantification of 53BP1+ radiation-induced foci (RIF) during the first 4-48 h post-irradiation was performed as a function of dose and LET in non-immortalized primary skin fibroblasts derived from 76 mice across 15 strains (5 inbred reference strains and 10 collaborative-cross strains) exposed to X rays (0.1, 1 and 4 Gy), 350 MeV/n 40Ar and 600 MeV/n 56Fe (1.1 and 3 particles/100sq. μm), as well as in peripheral blood mononuclear cells (PBMCs) from 768 healthy donors (matched ethnicity, 50/50 male/female, 18-70 years old) exposed to gamma rays (0.1 and 1 Gy), 350 MeV/n 28Si, 350 MeV/n 40Ar and 600 MeV/n 56Fe (1.1 and 3 particles/100sq. μm). A genome-wide association study (GWAS) was performed on the mouse strains between DNA damage responses to space radiation and single nucleotide polymorphisms (SNPs). We found SNPs, which were significantly associated to the RIF phenotype, mapped to genes and pathways that are functionally linked to health hazards for deep space exploration (e.g. carcinogenesis, nervous system damage and immune dysfunction). Some of these SNPs were located within protein coding regions, potentially interfering with protein functions and providing promising genetic targets for countermeasures. We also found correlations between both spontaneous and radiation-induced DNA damage and SNPs mapped to pathways associated with cellular metabolism. GWAS is undergoing for the human data. All data have been made available via the NASA Space Biology Open-Science database (genelab.nasa.gov) and we will discuss how various genomic and transcriptomic datasets can be accessed for modeling and integrated using machine learning methods for discovering new radiation biology.

Sylvain V Costes↗

NASA NTRS1995

Radiogenic cell transformation and carcinogenesis

Radiation carcinogenesis is one of the major biological effects considered important in the risk assessment for space travel. Various biological model systems, including both cultured cells and animals, have been found useful for studying the carcinogenic effects of space radiations, which consist of energetic electrons, protons and heavy ions. The development of techniques for studying neoplastic cell transformation in culture has made it possible to examine the cellular and molecular mechanisms of radiation carcinogenesis. Cultured cell systems are thus complementary to animal models. Many investigators have determined the oncogenic effects of ionizing and nonionizing radiation in cultured mammalian cells. One of the cell systems used most often for radiation transformation studies is mouse embryonic cells (C3H10T1/2), which are easy to culture and give good quantitative dose-response curves. Relative biological effectiveness (RBE) for heavy ions with various energies and linear energy transfer (LET) have been obtained with this cell system. Similar RBE and LET relationship was observed by investigators for other cell systems. In addition to RBE measurements, fundamental questions on repair of sub- and potential oncogenic lesions, direct and indirect effect, primary target and lesion, the importance of cell-cell interaction and the role of oncogenes and tumor suppressor genes in radiogenic carcinogenesis have been studied, and interesting results have been found. Recently several human epithelial cell systems have been developed, and ionizing radiation have been shown to transform these cells. Oncogenic transformation of these cells, however, requires a long expression time and/or multiple radiation exposures. Limited experimental data indicate high-LET heavy ions can be more effective than low-LET radiation in inducing cell transformation. Cytogenetic and molecular analyses can be performed with cloned transformants to provide insights into basic genetic mechanism(s) of radiogenic transformation of human epithelial cells.

NASA Discipline Radiation Health↗

NASA NTRS1999

GH/IGF-I Transgene Expression on Muscle Homeostasis

We propose to test the hypothesis that the growth hormone/ insulin like growth factor-I axis through autocrine/paracrine mechanisms may provide long term muscle homeostasis under conditions of prolonged weightlessness. As a key alternative to hormone replacement therapy, ectopic production of hGH, growth hormone releasing hormone (GHRH), and IGF-I will be studied for its potential on muscle mass impact in transgenic mice under simulated microgravity. Expression of either hGH or IGF-I would provide a chronic source of a growth-promoting protein whose biosynthesis or secretion is shut down in space. Muscle expression of the IGF-I transgene has demonstrated about a 20% increase in hind limb muscle mass over control nontransgenic litter mates. These recent experiments, also establish the utility of hind-limb suspension in mice as a workable model to study atrophy in weight bearing muscles. Thus, transgenic mice will be used in hind-limb suspension models to determine the role of GH/IGF-I on maintenance of muscle mass and whether concentric exercises might act in synergy with hormone treatment. As a means to engineer and ensure long-term protein production that would be workable in humans, gene therapy technology will be used by to monitor muscle mass preservation during hind-limb suspension, after direct intramuscular injection of a genetically engineered muscle-specific vector expressing GHRH. Effects of this gene-based therapy will be assessed in both fast twitch (medial gastrocnemius) and slow twitch muscle (soleus). End-points include muscle size, ultrastructure, fiber type, and contractile function, in normal animals, hind limb suspension, and reambutation.

Schwartz, Robert J.↗

NASA NTRS2003

Tactical Maneuvering Using Immunized Sequence Selection

This paper describes a tactical maneuvering system that uses an artificial immune system based approach for selecting maneuver sequences. This approach combines the problem solving abilities of genetic algorithms with the memory retention characteristics of an immune system. Of significant importance here is the fact that the tactical maneuvering system can make time-critical decisions to accomplish near-term objectives within a dynamic environment. These objectives can be received from a human operator, autonomous executive, or various flight planning specialists. Simulation tests were performed using a high performance military aircraft model. Results demonstrate the potential of using immunized sequence selection in order to accomplish tactical maneuvering objectives ranging from flying to a location while avoiding unforeseen obstacles, to performing relative positioning in support of air combat maneuvering.

Kaneshige, John↗

NASA NTRS1999

Molecular Mechanisms Regulating Muscle Fiber Composition Under Microgravity

The overall goal of this project is to reveal the molecular mechanisms underlying the selective and debilitating atrophy of specific skeletal muscle fiber types that accompanies sustained conditions of microgravity. Since little is currently known about the regulation of fiber-specific gene expression programs in mammalian muscle, elucidation of the basic mechanisms of fiber diversification is a necessary prerequisite to the generation of therapeutic strategies for attenuation of muscle atrophy on earth or in space. Vertebrate skeletal muscle development involves the fusion of undifferentiated mononucleated myoblasts to form multinucleated myofibers, with a concomitant activation of muscle-specific genes encoding proteins that form the force-generating contractile apparatus. The regulatory circuitry controlling skeletal muscle gene expression has been well studied in a number of vertebrate animal systems. The goal of this project has been to achieve a similar level of understanding of the mechanisms underlying the further specification of muscles into different fiber types, and the role played by innervation and physical activity in the maintenance and adaptation of different fiber phenotypes into adulthood. Our recent research on the genetic basis of fiber specificity has focused on the emergence of mature fiber types and have implicated a group of transcriptional regulatory proteins, known as E proteins, in the control of fiber specificity. The restriction of E proteins to selected muscle fiber types is an attractive hypothetical mechanism for the generation of muscle fiber-specific patterns of gene expression. To date our results support a model wherein different E proteins are selectively expressed in muscle cells to determine fiber-restricted gene expression. These studies are a first step to define the molecular mechanisms responsible for the shifts in fiber type under conditions of microgravity, and to determine the potential importance of E proteins as upstream targets for the effects of weightlessness. In the past year we have determined that the expression of E Proteins is restricted to specific fiber types by post-transcriptional mechanisms. By far, the most prevalent mechanism of cellular control for achieving post-transcriptional regulation of gene expression is selective proteolysis -through the ubiquitin -proteasome pathway. Steady-state levels of HEB message are similar in all fast and slow skeletal muscle fiber types, yet the protein is restricted to Type IIX fibers. HEB appears to be a nodal point for regulating fiber-specific transcription, as expression of the transcription factor is regulated at the post-transcriptional level. It is not clear at present whether the regulation is at the level of protein synthesis or degradation. We are now poised to evaluate the biological role of ubiquitination in fiber specific-gene expression by controlling the post-transcriptional expression of E Proteins. The use of metabolic labelling and pharmacological inhibitors of the ubiquitin pathway will be used to identify the mode of regulation of the Type IIX expression pattern. The potential role of specific kinases in effecting the restriction of HEB expression will be examined by using both inhibitors and activators. The results of these studies will provide the necessary information to evaluate the biological role of E proteins in controlling fiber type transitions, and in potentially attenuating the atrophic effects of microgravity conditions. We have also recently shown that ectopic expression of the HEB protein transactivates the Type IIX-specific skeletal a-actin reporter. The 218 bp skeletal a-actin promoter drives transgene expression solely in mature Type IIX fibers. A mouse also carrying the transgene MLCI/HEB (which ectopically expresses the E Protein HEB in Type IIB fibers) forces expression of the skeletal a-actin reporter gene in Type IIB fibers. We can now dissect the composition of this fiber-specific cis-element. The skeletal a-actin promoter is quite compact and has been extensively characterized in vitro for activity and binding factors. The single E box may act as a binding target of myogenic factor/HEB heterodimer to allow for IIX expression. The HEB transcription factor may recognize either the precise flanking sequences of the E Box, or perhaps interacting with other proteins bound nearby, and activating expression in Type IIX fibers. This E box will be both ablated, and alternatively, as ablation may well destroy any muscle-specific transcriptional activity, flanking sequences substituted with those surrounding the E box (El) of the myogenin promoter. Modification of fiber-specific transgene expression will be tested in transgenic mice. The results of these studies will provide basic information on the regulatory circuitry underlying fiber specificity, and will form the basis for building appropriate transgenic regulatory cassettes to effect fiber transitions in subsequent experimental manipulations on unweighted muscles.

Rosenthal, Nadia A.↗

NASA NTRS1993

Partial melting of ordinary chondrites: Lost City (H) and St. Severin (LL)

Eucrites and diogenites are examples of asteroidal basalts and orthopyroxenites, respectively. As they are found intermingled in howardites, which are inferred to be regolith breccias, eucrites and diogenites are thought to be genetically related. But the details of this relationship and of their individual origins remain controversial. Work by Jurewicz et al. showed that 1170-1180 C partial melts of the (anhydrous) Murchison (CM) chondrite have major element compositions extremely similar to primitive eucrites, such as Sioux County. However, the MnO contents of these melts were about half that of Sioux County, a problem for the simple partial melting model. In addition, partial melting of Murchison could not produce diogenites, because residual pyroxenes in the Murchison experiments were too Fe- and Ca-rich and were minor phases at all but the lowest temperatures. A parent magma for diogenites needs an expanded low-calcium pyroxene field. In their partial melting study of an L6 chondrite, Kushiro and Mysen found that ordinary chondrites did have an expanded low-Ca pyroxene field over that of CV chondrites (i.e., Allende), probably because ordinary chondrites have lower Mg/Si ratios. This study expands that of both Kushiro and Mysen and Jurewicz et al. to the Lost City (H) and St. Severin (LL) chondrites at temperatures ranging from 1170 to 1325 C, at an fO2 of one log unit below the iron-wuestite buffer (IW-1).

Jurewicz, Amy J. G.↗

NASA NTRS1998

The molecular basis of ethylene signalling in Arabidopsis

The simple gas ethylene profoundly influences plants at nearly every stage of growth and development. In the past ten years, the use of a genetic approach, based on the triple response phenotype, has been a powerful tool for investigating the molecular events that underlie these effects. Several fundamental elements of the pathway have been described: a receptor with homology to bacterial two-component histidine kinases (ETR1), elements of a MAP kinase cascade (CTR1) and a putative transcription factor (EIN3). Taken together, these elements can be assembled into a simple, linear model for ethylene signalling that accounts for most of the well-characterized ethylene mediated responses.

Non-NASA Center↗

NASA NTRS1998

The effect of track structure on the induction of chromosomal aberrations in murine cells

PURPOSE: To measure chromosome aberrations in C3H 10T1/2 mouse fibroblasts using FISH painting at the first mitosis following exposure to 30 keV/microm hydrogen or neon ions. MATERIALS AND METHODS: Cells in plateau-phase were irradiated with 0.86 MeV protons at the TTT-3 Tandem accelerator in Naples (Italy), or with 400 MeV/n Ne ions at the HIMAC accelerator in Chiba (Japan). Colcemid-blocked cells were harvested at the first mitosis following exposure, and chromosome spreads were hybridized in situ with a fluorescein-labelled composite mouse DNA probe specific for chromosomes 2 and 8. RESULTS: Protons were more efficient than neon ions at the same LET in the induction of chromosome interchanges and breaks. Yields of complex exchanges were similar for both particles at the same dose, but protons produced mostly insertions, while with Ne exposure non-reciprocal exchanges were the most frequent complex-type exchange. CONCLUSIONS: Charged particles with the same LET produce different yields of chromosome aberrations, and some observed differences can be explained based on the available track-structure models.

NASA Center JSC↗

NASA NTRSDate not supplied

Bioreactor Development for CO2-Based In Situ Resource Utilization Manufacturing

Sustainable long-duration manned missions on both the Moon and Mars will require in situ resource utilization (ISRU). Carbon dioxide (CO2) has great potential as a harvestable resource, making up 95% of the atmosphere on Mars and being produced as respiratory waste in spacecraft and future planetary habitats. Through ISRU, biomanufacturing has the capability to produce a near limitless array of products from local space resources. Here, a CO2-based ISRU recombinant protein producing bioreactor and associated biomanufacturing organisms were designed to produce a highly stable carbonic anhydrase (CA). Candidate organisms were selected by growth characterization on acetate and formic acid, carbon substrates that are synthesized via electrochemical conversion of CO2. To improve growth on the CO2 producing substrate formic acid and for direct integration of ISRU CO2, a synthetic Calvin-Benson-Bassam cycle was designed for use in Escherichia coli. Multiplex genetic modification in E. coli was facilitated by a tailored CRISPR/Cas9 and λ red recombineering two-vector system. For expression of CA, a blue light regulated T7 promoter was employed for dynamic and small molecule free induction. Efficient bioproduction through a fed-batch exponential feeding strategy was determined via mass balance analysis from ISRU substrates to biomass and CA yield. Flux balance analysis was used to model ISRU substrate metabolism and metabolic pathway engineering in candidate organisms under cultivation strategy conditions for both metabolism reconstruction and pathway design optimization. Finally, a small-scale, disposable bag bioreactor for use in the NASA Bioculture System infrastructure was designed to enable CO2-based CA biomanufacturing in reduced-gravity environments.

biomanufacturing↗

NASA NTRS1996

From the Primitive Atmosphere to the Prebiotic Soup to the Pre-RNA World

Organic compounds would have been produced in an earth's atmosphere that was reducing. The soup would contain amino and hydroxy acids, together with smaller amounts of purines and pyrimidines. The presence' of sugars is less likely, although they can be produced by the formose reaction from formaldehyde. However, the prebiotic synthesis of RNA has not been demonstrated. One problem is that ribose is not produced selectively over other pentoses and hexoses, except under special conditions. The second problem is that ribose is unstable, with a half-life at pH7 and 100 C of 73 minutes (44 years at 0 C). Other sugars are similarly unstable. Another problem is that there is no efficient prebiotic synthesis of polyphosphates, nor the glycosidic bond of nucleosides. This suggests that there may have been an informational macromolecule that preceded RNA. The RNA world refers to the time when RNA carried both the genetic information and the catalytic activity, and was subsequently converted to the DNA/protein world when protein synthesis began. Preceeding the RNA world was the Pre-RNA world, where a backbone different from ribose phosphate was used, and the bases may have been different from adenine, uracil, guanine and cytosine. We have shown recently that cytosine and uracil can be synthesized efficiently under prebiotic conditions using a dried lagoon model instead of the usual dilute ocean hypothesis. In addition, we have shown that uracil adds formaldehyde efficiently to give 5- hydroxymethyl uracil, which in turn adds various nucleophiles to give uracil analogs of most of the amino acids that occur in proteins. For example, the ammonia, guanidine and imidazole adducts from the analogs of lysine, arginine and histidine. This suggests that the catalytic potential of RNA may have been much more extensive than previously assumed. The major problem is finding out what was the precursor to the ribose phosphate backbone. This will be the key to developing prebiotic self-replicating systems.

Miller, Stanley L.↗

NASA NTRS2006

In-Space Radiator Shape Optimization using Genetic Algorithms

Future space exploration missions will require the development of more advanced in-space radiators. These radiators should be highly efficient and lightweight, deployable heat rejection systems. Typical radiators for in-space heat mitigation commonly comprise a substantial portion of the total vehicle mass. A small mass savings of even 5-10% can greatly improve vehicle performance. The objective of this paper is to present the development of detailed tools for the analysis and design of in-space radiators using evolutionary computation techniques. The optimality criterion is defined as a two-dimensional radiator with a shape demonstrating the smallest mass for the greatest overall heat transfer, thus the end result is a set of highly functional radiator designs. This cross-disciplinary work combines topology optimization and thermal analysis design by means of a genetic algorithm The proposed design tool consists of the following steps; design parameterization based on the exterior boundary of the radiator, objective function definition (mass minimization and heat loss maximization), objective function evaluation via finite element analysis (thermal radiation analysis) and optimization based on evolutionary algorithms. The radiator design problem is defined as follows: the input force is a driving temperature and the output reaction is heat loss. Appropriate modeling of the space environment is added to capture its effect on the radiator. The design parameters chosen for this radiator shape optimization problem fall into two classes, variable height along the width of the radiator and a spline curve defining the -material boundary of the radiator. The implementation of multiple design parameter schemes allows the user to have more confidence in the radiator optimization tool upon demonstration of convergence between the two design parameter schemes. This tool easily allows the user to manipulate the driving temperature regions thus permitting detailed design of in-space radiators for unique situations. Preliminary results indicate an optimized shape following that of the temperature distribution regions in the "cooler" portions of the radiator. The results closely follow the expected radiator shape.

Hull, Patrick V.↗

NASA NTRSDate not supplied

Bioreactor Development for CO2-Based In Situ Resource Utilization Manufacturing

Sustainable long-duration manned missions on both the Moon and Mars will require in situ resource utilization (ISRU). Carbon dioxide (CO2) has great potential as a harvestable resource, making up 95% of the atmosphere on Mars and being produced as respiratory waste in spacecraft and future planetary habitats. Through ISRU, biomanufacturing has the capability to produce a near limitless array of products from local space resources, which include pharmaceuticals, bioplastics, chemical feedstocks, and industrial enzymes. Here, a CO2-based ISRU recombinant protein bioreactor and associated biomanufacturing organisms were designed to produce a highly stable carbonic anhydrase (CA). Initial work characterized candidate organisms for growth on acetate and formic acid, carbon substrates that can be synthesized via electrochemical conversion of CO2. To improve growth on the CO2 producing substrate formic acid and for direct integration of ISRU CO2, a synthetic Calvin-Benson-Bassam cycle was designed for use in Cyberlindnera jadinii and Escherichia coli. Genetic modifications in E. coli will be facilitated by a tailored CRISPR/Cas9 and λ red recombineering two-vector system. For expression of CA, a blue light regulated T7 promoter was employed for dynamic and small molecule free induction. Efficient bioproduction through a fed-batch exponential feeding strategy was determined via mass balance calculations from ISRU substrates to biomass and CA yield. Flux balance analysis was used to model ISRU substrate metabolism and metabolic pathway engineering in candidate organisms under cultivation strategy conditions for both metabolism reconstruction and pathway design optimization. Finally, a small-scale, disposable bag bioreactor concept for use in the NASA Bioculture System infrastructure was designed to enable CO2-based CA production in reduced-gravity environments.

Biomanufacturing, Pathway Engineering, Flux Balanc↗

NASA NTRS2022

A Closer Look at Non-Random Patterns Within Chemistry Space for a Smaller, Earlier Amino Acid Alphabet

Recent findings, in vitro and in silico, are strengthening the idea of a simpler, earlier stage of genetically encoded proteins which used amino acids produced by prebiotic chemistry. These findings motivate a re-examination of prior work which has identified unusual properties of the set of twenty amino acids found within the full genetic code, while leaving it unclear whether similar patterns also characterize the subset of prebiotically plausible amino acids. We have suggested previously that this ambiguity may result from the low number of amino acids recognized by the definition of prebiotic plausibility used for the analysis. Here, we test this hypothesis using significantly updated data for organic material detected within meteorites, which contain several coded and non-coded amino acids absent from prior studies. In addition to confirming the well-established idea that “late” arriving amino acids expanded the chemistry space encoded by genetic material, we find that a prebiotically plausible subset of coded amino acids generally emulates the patterns found in the full set of 20, namely an exceptionally broad and even distribution of volumes and an exceptionally even distribution of hydrophobicities (quantified as logP) over a narrow range. However, the strength of this pattern varies depending on both the size and composition the library used to create a background (null model) for a random alphabet, and the precise definition of exactly which amino acids were present in a simpler, earlier code. Findings support the idea that a small sample size of amino acids caused previous ambiguous results, and further improvements in meteorite analysis, and/or prebiotic simulations will further clarify the nature and extent of unusual properties. We discuss the case of sulfur-containing amino acids as a specific and clear example and conclude by reviewing the potential impact of better understanding the chemical “logic” of a smaller forerunner to the standard amino acid alphabet.

Amino acids↗

NASA NTRS1986

Implications of the inferred compositions of asteroids for their collisional evolution

The inferred compositions of mainbelt asteroids set constraints on the nature and degree of collisional evolution of the asteroids. The existence of a basaltic crust on 4 Vesta seems to require that there has been very little collisional evolution since the presumably ancient solidification of its crust, which is consistent with most recent models of collisional evolution. But interpretations of the compositions of M- and S-type asteroids as collisionally stripped cores of differentiated parent bodies argue for much more extensive collisions. A major problem is presented by the extreme rarity of olivine-rich asteroids and olivine meteorites. Studies of the compositions of members of dynamical families suggest that most supposed families are either not real, or at least are not genetically related fragments of a cosmochemically reasonable precursor body. The mutual incompatibilities among various 'accepted' traits of the asteroids deserve further study in order to develop a self-consistent scenario for the chemical and physical evolution of the asteroids.

Chapman, C. R.↗