Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “Gene expression”

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 415 records · Page 23
All sourcesNASA NTRSDOE OSTI
NASA NTRS2014

Delivery of Probiotics in the Space Food System

The addition of probiotic bacteria to the space food system is expected to confer immunostimulatory benefits on crewmembers during spaceflight, counteracting the immune dysregulation that has been documented in spaceflight [1]. Specifically, the probiotic Lactobacillus acidophilus has been shown to promote health benefits including antagonism towards and inhibition of virulence related gene expression in pathogens, mucosal stimulation of immune cells, and a reduction in the occurrence and duration of cold and flu-like symptoms [2-5]. The optimum delivery system for probiotics has not been determined for spaceflight, where the food system is shelf stable and the lack of refrigeration prevents the use of traditional dairy delivery methods. This work proposes to determine whether L. acidophilus is more viable, and therefore more likely to confer immune benefit, when delivered in a capsule form or when delivered in nonfat dry milk powder with a resuscitation opportunity upon rehydration, following 0, 4, and 8 months of storage at -80degC, 4degC, and 22degC, and both prior to and after challenge with simulated gastric and intestinal juices. We hypothesize that the low moisture neutral dairy matrix provided by the nonfat dry milk, and the rehydration step prior to consumption, will extend probiotic viability and stress tolerance compared to a capsule during potential storage conditions in spaceflight and in simulated digestion conditions.

Castro, S. L.↗
NASA NTRS2014

Delivery of Probiotics in the Space Food System

The addition of probiotic bacteria to the space food system is expected to confer immunostimulatory benefits on crewmembers during spaceflight, counteracting the immune dysregulation that has been documented in spaceflight. Specifically, the probiotic Lactobacillus acidophilus has been shown to promote health benefits including antagonism towards and inhibition of virulence related gene expression in pathogens, mucosal stimulation of immune cells, and a reduction in the occurrence and duration of cold and flu‐like symptoms. The optimum delivery system for probiotics has not been determined for spaceflight, where the food system is shelf stable and the lack of refrigeration prevents the use of traditional dairy delivery methods. This work proposes to determine whether L. acidophilus is more viable, and therefore more likely to confer immune benefit, when delivered in a capsule form or when delivered in nonfat dry milk powder with a resuscitation opportunity upon rehydration, following 0, 4, and 8 months of storage at ‐80degC, 4degC, and 22degC, and both prior to and after challenge with simulated gastric and intestinal juices. We hypothesize that the low moisture neutral dairy matrix provided by the nonfat dry milk, and the rehydration step prior to consumption, will extend probiotic viability and stress tolerance compared to a capsule during potential storage conditions in spaceflight and in simulated digestion conditions.

Castro, S. L.↗
NASA NTRS2014

Spaceflight Microbiology: Benefits for Long Duration Spaceflight and Our Understanding of Microorganisms on Earth

Spaceflight microbiology is composed of both operational and experimental components that complement each other in our understanding of microbial interactions and their responses in the microgravity of spaceflight. Operationally, efforts to mitigate microbiological risk to the crew and the spacecraft have historically focused on minimizing the number of detectable organisms, relying heavily on preventative measures, including appropriate vehicle design, crew quarantine prior to flight, and stringent microbial monitoring. Preflight monitoring targets have included the astronauts, spaceflight foods, potable water systems, the vehicle air and surfaces, and the cargo carried aboard the spacecraft. This approach has been very successful for earlier missions; however, the construction and long-term habitation of the International Space Station (ISS) has created the need for additional inflight monitoring of the environment and potable water systems using hardware designed for both in-flight microbial enumeration and sample collection and return to Earth. In addition to operational activities, the ISS is providing a research platform to advance our understanding of microbiomes in the built environment. Adding to the research possibilities of this system are multiple reports of unique changes in microbial gene expression and phenotypic responses, including virulence and biofilm formation, in response to spaceflight culture. The tremendous potential of the ISS research platform led the National Research Council to recommend that NASA utilize the ISS as a microbial observatory. Collectively, the findings from operational and research activities on the ISS are expected to both enable future space exploration and translate to basic and applied research on Earth.

Ott, C. Mark↗
NASA NTRS2014

Probiotics in the Space Food System: Delivery, Microgravity Effects, and the Potential Benefit to Crew Health

As mission distance and duration increase, the need grows for non‐invasive disease prevention and immunomodulation, especially given the limited medical response capability expected for these missions and the immune dysregulation documented in crew. Additionally, changes in diet, lifestyle, antibiotic usage, and the environmental stresses during spaceflight may alter crewmembers' intestinal microbiome. The addition of probiotic bacteria to the space food system is expected to confer immunostimulatory benefits on crewmembers, with the potential to counteract the immune dysregulation that has been documented in spaceflight. Based on previous studies that demonstrated unique microbiological responses to the low shear environment of spaceflight, probiotic organisms hold the potential to induce enhanced beneficial responses through mechanisms, such as beneficial interactions with human immune cells and repression of colonization of pathogens on the mucosa. The work presented here will begin to address two research gaps related to providing probiotics in spaceflight: 1) delivery, and 2) the effect of the low shear microgravity environment on probiotic attributes. The probiotic Lactobacillus acidophilus was selected for investigation due to its wide commercial use and documented benefits that include inhibition of virulence related gene expression in pathogens and mucosal stimulation of immune cells. The delivery system for probiotics has not been determined for spaceflight, where the food system is shelf stable and the lack of refrigeration prevents the use of traditional dairy delivery methods. In order to demonstrate the potential of the space food system to deliver viable probiotic bacteria to crewmembers, the probiotic L. acidophilus was packaged in high barrier flight packaging in nonfat dry milk (NFDM) or retained in commercial capsule form. Viable cells were enumerated over 8 months of storage at 22, 4, and ‐80ºC. The survival of L. acidophilus rehydrated in NFDM, in a PBS control, and directly from the capsule was also evaluated following stress challenge with simulated gastric and intestinal juices to determine the method that would deliver the most viable cells to the intestine, where they would be expected to confer beneficial effects. L. acidophilus was found to be stable to gastric and intestinal juice challenge when delivered in rehydrated NFDM, even after two hours of exposure. In comparison, L. acidophilus was reduced by 1‐5 logs when exposed to gastric and intestinal juice directly and when rehydrated in a PBS control. Shelf life data indicated that L. acidophilus would require refrigerated or frozen storage to remain viable at adequate levels over the multi‐year storage periods required for spaceflight. This study suggests that the protective effect provided by the dairy matrix, and not merely rehydration prior to consumption, extends probiotic viability and stress tolerance during storage in spaceflight and in simulated digestion conditions more adequately than a capsule. In addition to effective delivery, it is essential to understand the microgravity effects on the stress tolerances and genetic expression of probiotic bacteria to enable optimization of growth, survival, strain selection, and conferred benefits in spaceflight. In our current study, ground‐based characterization of the growth, stress response, and transcriptomic response of L. acidophilus will be accomplished using the low shear modeled microgravity (LSMMG) culture environment in the rotating wall vessel (RWV). We hypothesize that L. acidophilus will maintain or improve its growth and stress response following culture in the LSMMG environment, and that transcriptomic analysis will define the associated molecular mechanism(s), resulting in the ability to optimize strain selection.

Castro, S. L.↗
NASA NTRS2014

Maximizing Science Return from Future Rodent Experiments on the International Space Station (ISS): Tissue Preservation

To better understand how mammals adapt to long duration habitation in space, a system for performing rodent experiments on the ISS is under development; Rodent Research-1 is the first flight and will include validation of both on-orbit animal support and tissue preservation. To evaluate plans for on-orbit sample dissection and preservation, we simulated conditions for euthanasia, tissue dissection, and prolonged sample storage on the ISS, and we also developed methods for post-flight dissection and recovery of high quality RNA from multiple tissues following prolonged storage in situ for future science. Mouse livers and spleens were harvested under conditions that simulated nominal, on-orbit euthanasia and dissection operations including storage at -80 C for 4 months. The RNA recovered was of high quality (RNA Integrity Number, RIN(is) greater than 8) and quantity, and the liver enzyme contents and activities (catalase, glutathione reductase, GAPDH) were similar to positive controls, which were collected under standard laboratory conditions. We also assessed the impact of possible delayed on-orbit dissection scenarios (off-nominal) by dissecting and preserving the spleen (RNAlater) and liver (fast-freezing) at various time points post-euthanasia (from 5 min up to 105 min). The RNA recovered was of high quality (spleen, RIN (is) greater than 8; liver, RIN (is) greater than 6) and liver enzyme activities were similar to positive controls at all time points, although an apparent decline in select enzyme activities was evident at the latest time (105 min). Additionally, various tissues were harvested from either intact or partially dissected, frozen carcasses after storage for approximately 2 months; most of the tissues (brain, heart, kidney, eye, adrenal glands and muscle) were of acceptable RNA quality for science return, whereas some tissues (small intestine, bone marrow and bones) were not. These data demonstrate: 1) The protocols developed for future flight experiments will support science return despite delayed preservation post-euthanasia or prolonged storage, and 2) Many additional tissues for gene expression analysis can be obtained by dissection following prolonged storage of the tissue in situ at -80 C. These findings have relevance both to high value, ground-based experiments when sample collection capability is severely constrained, and to all future spaceflight experiments that entail on-orbit sample recovery by the ISS crew.

tissues↗
NASA NTRS2015

Omics Research on the International Space Station

The International Space Station (ISS) is an orbiting laboratory whose goals include advancing science and technology research. Completion of ISS assembly ushered a new era focused on utilization, encompassing multiple disciplines such as Biology and Biotechnology, Physical Sciences, Technology Development and Demonstration, Human Research, Earth and Space Sciences, and Educational Activities. The research complement planned for upcoming ISS Expeditions 45&46 includes several investigations in the new field of omics, which aims to collectively characterize sets of biomolecules (e.g., genomic, epigenomic, transcriptomic, proteomic, and metabolomic products) that translate into organismic structure and function. For example, Multi‐Omics is a JAXA investigation that analyzes human microbial metabolic cross‐talk in the space ecosystem by evaluating data from immune dysregulation biomarkers, metabolic profiles, and microbiota composition. The NASA OsteoOmics investigation studies gravitational regulation of osteoblast genomics and metabolism. Tissue Regeneration uses pan‐omics approaches with cells cultured in bioreactors to characterize factors involved in mammalian bone tissue regeneration in microgravity. Rodent Research‐3 includes an experiment that implements pan‐omics to evaluate therapeutically significant molecular circuits, markers, and biomaterials associated with microgravity wound healing and tissue regeneration in bone defective rodents. The JAXA Mouse Epigenetics investigation examines molecular alterations in organ specific gene expression patterns and epigenetic modifications, and analyzes murine germ cell development during long term spaceflight. Lastly, Twins Study ("Differential effects of homozygous twin astronauts associated with differences in exposure to spaceflight factors"), NASA's first foray into human omics research, applies integrated analyses to assess biomolecular responses to physical, physiological, and environmental stressors associated with spaceflight.

Love, John↗
NASA NTRS2015

NASA Space Radiation Risk Project: Overview and Recent Results

The NASA Space Radiation Risk project is responsible for integrating new experimental and computational results into models to predict risk of cancer and acute radiation syndrome (ARS) for use in mission planning and systems design, as well as current space operations. The project has several parallel efforts focused on proving NASA's radiation risk projection capability in both the near and long term. This presentation will give an overview, with select results from these efforts including the following topics: verification, validation, and streamlining the transition of models to use in decision making; relative biological effectiveness and dose rate effect estimation using a combination of stochastic track structure simulations, DNA damage model calculations and experimental data; ARS model improvements; pathway analysis from gene expression data sets; solar particle event probabilistic exposure calculation including correlated uncertainties for use in design optimization.

Blattnig, Steve R.↗
NASA NTRS2016

Transgenic Mouse Model for Reducing Oxidative Damage in Bone

Bone loss can occur due to many challenges such age, radiation, microgravity, and Reactive Oxygen Species (ROS) play a critical role in bone resorption by osteoclasts (Bartell et al. 2014). We hypothesize that suppression of excess ROS in skeletal cells, both osteoblasts and osteoclasts, regulates skeletal growth and remodeling. To test our hypothesis, we used transgenic mCAT mice which overexpress the human anti-oxidant catalase gene targeted to the mitochondria, the main site for endogenous ROS production. mCAT mice have a longer life-span than wildtype controls and have been used to study various age-related disorders. To stimulate remodeling, 16 week old mCAT mice or wildtype mice were exposed to treatment (hindlimb-unloading and total body-irradiation) or sham treatment conditions (control). Tissues were harvested 2 weeks later for skeletal analysis (microcomputed tomography), biochemical analysis (gene expression and oxidative damage measurements), and ex vivo bone marrow derived cell culture (osteoblastogenesis and osteoclastogenesis). mCAT mice expressed the transgene and displayed elevated catalase activity in skeletal tissue and marrow-derived osteoblasts and osteoclasts grown ex vivo. In addition, when challenged with treatment, bone tissues from wildtype mice showed elevated levels of malondialdehyde (MDA), indicating oxidative damage) whereas mCAT mice did not. Correlation analysis revealed that increased catalase activity significantly correlated with decreased MDA levels and that increased oxidative damage correlated with decreased percent bone volume (BVTV). In addition, ex-vivo cultured osteoblast colony growth correlated with catalase activity in the osteoblasts. Thus, we showed that these transgenic mice can be used as a model to study the relationship between markers of oxidative damage and skeletal properties. mCAT mice displayed reduced BVTV and trabecular number relative to wildtype mice, as well as increased structural model index in the cancellous tibia. Treatment caused bone loss in wildtype mice, as expected. Treatment also caused deficits in microarchitecture of mCAT mice, although less severe than wildtype mice in some parameters (percent bone volume, structural model index and cortical area). In conclusion, our results indicate that endogenous ROS signaling in both osteoblast and osteoclast lineage cells contributes to skeletal growth and remodeling, and quenching oxidative damage could play a role in bone loss prevention.

transgenic mice↗
NASA NTRS2016

Risk of Adverse Health Effects Due to Host-Microorganism Interactions

Numerous spaceflight experiments have been conducted to investigate alterations in microbial responses resulting from culture during spaceflight and spaceflight-analogs. However, recent studies investigating spaceflight-associated alterations in microbial virulence have initiated the review and production of evidence to better understand the impact these alterations would have on the incidence of infectious disease during a spaceflight exploration mission. The preponderance of evidence indicates that alterations in microbial gene expression and phenotype (including virulence) are occurring; however, the clinical implications of such changes are still unclear. Greater knowledge is required including a better understanding of the mechanism behind unique spaceflight-associated microbial responses to determine how this environmental stimulus impacts various microorganisms, their diversity and concentration in the spacecraft and crew microbiome, their impact on the vehicle and crew, and their resistance to current mitigation and antibiotic regimens. This knowledge will enable us to determine requirements, guidelines, and processes for design and monitoring of the next generation vehicles.

Ott, C. Mark↗
NASA NTRS2017

Association Between Vascular Density and Loss of Protective RAS During Early NPDR by Fractal Dimension

Purpose: Our hypothesis predicts that blood vessels within the retina increase in density during early-stage nonproliferative diabetic retinopathy (NPDR), based on previous results of a small retrospective study. For the current prospective study, the remodeling of arteries and veins during progression of early NPDR is assessed by a repertoire of parameters that includes the fractal dimension (D(sub f) ). In complex structures such as branching vascular trees, D(sub f) is a sensitive measure of space-filing capacity. The renin-angiotensin system (RAS) is implicated in DR pathogenesis and the function of circulating angiogenic cells (CACs), a critical bone marrow-derived population instrumental in vascular repair. Methods: Arterial and venous branching patterns were extracted from images of 6 normal controls and 3 early NPDR subjects (2 moderate, 1 mild) acquired by Heidelberg Spectralis (Registered Trademark) OCT following fluorescein angiography (FA). The vascular branching patterns were analyzed by NASAs VESsel GENeration Analysis (VESGEN) software, in which skeletonized representations were generated automatically to yield D(sub f) by the box-counting method. For binary 2D images, D(sub f) varies between limiting Euclidean dimensions of 1 and 2. Peripheral blood of diabetics and controls was collected for CD34+ CAC isolation. The gene expression of RAS in CACs was assessed by qPCR for Mas receptor to Ang-(1-7). The vasoreparative function of the CACs was measured by migration ability toward CXCL12 (SDF-1). Results: By D(sub f), venous and arterial densities were 1.370 +/- 0.006 and 1.329 +/- 0.016 for early NPDR, compared to 1.318 +/- 0.012 and 1.320 +/- 0.036 for control. The space filling capacity in early NPDR measured by D(sub f), a sensitive parameter, therefore demonstrated a pronounced increase for veins, but not for arteries. Mas receptor mRNA in CACs was increased in diabetics without DR but reduced with onset of NPDR, indicating possible loss of compensation of protective RAS during early DR. Migratory dysfunction of CD34+ cells was further associated with DR. Conclusions: As assessed by the fractal dimension in our preliminary study, the space-filling capacity of veins, but not arteries, was greater in early NPDR than in control. Larger patient populations will be examined as we complete our ongoing longitudinal study. Results further suggest the protective RAS axis within diabetic CACs is lost early in DR and is associated with increased vascular remodeling as evidenced by VESGEN analysis.

vascular↗
NASA NTRS2017

Effects of Simulated Microgravity on a Host-Pathogen System

While it has been shown that decades of astronauts and cosmonauts can suffer from illnesses both during and after spaceflight, the underlying causes are still poorly understood, due in part to the fact that there are so many variables to consider when investigating the human immune system in a complex environment. Invertebrates have become popular models for studying human disease because they are cheap, highly amenable to experimental manipulation, and have innate immune systems with a high genetic similarity to humans. Fruit flies (Drosophila melanogaster) have been shown to experience a dramatic shift in immune gene expression following spaceflight, but are still able to fight off infections when exposed to bacteria. However, the common bacterial pathogen Serratia marcescens was shown to become more lethal to fruit flies after being cultured in space, suggesting that not only do we need to consider host changes in susceptibility, but also changes in the pathogen itself after spaceflight conditions. Being able to simulate spaceflight conditions in a controlled environment on the ground gives us the ability to not only evaluate the effects of microgravity on the host immune system, but also how the microorganisms that cause immune disorders are being affected by these drastic environmental shifts. In this study, I use a ground-based simulated microgravity environment to examine the genetic changes associated with increased S. marcescens virulence in order to understand how microgravity is affecting this pathogen, as well as how these genetic changes influence and interact with the host immune system. This study will provide us with more directed approaches to studying the effects of spaceflight on human beings, with the ultimate goal of being able to counteract immune dysfunction in future space exploration.

Immunology↗
NASA NTRS2017

Development of a Novel Space Flight Plan to Monitor Female Mice Fertility Using Reduced Crew Time

Ovarian estrogen impacts the normal homeostatic and metabolic processes of all tissues and organ systems within the body: particularly, but not limited to canonical space-flight impacted systems: bone, muscle, immune, wound repair, and cardiovascular. Effects of space flight on the ovarian estrogen production are therefore critical to our understanding of all space flight experiments using female mice, the current paradigm being used on the International Space Station (ISS). Recently, we demonstrated that vaginal wall histology could be used to determine the stage of the estrous cycle in female mice at the time of sacrifice in space. Moreover, this robust technique was completed following two post-flight freezethaw procedures of the carcasses (RR1 experiment). Thus, this technique represents a viable mechanism to determine the estrous cycle status of the female at the time of sacrifice and can be completed in a manner that does not impact primary experimental objectives. We propose that vaginal wall histology become a standard procedure completed on all mice sacrificed in space and that the individual estrous status of each animal be shared with all investigators. While evidence of estrous cyclicity was present in long-term (33 day) RR1 mice, fertility of female mice exposed to weightlessness remains unknown. In preparation for an upcoming funded NASA flight investigating the effects of long duration spaceflight on female fertility, we have refined our experimental design to minimize crew flight time and to accommodate the duration of Dragon capsule berth. These refinements maintain all our proposed primary and secondary experimental objectives. Briefly, in order to evaluate fertility, we will super ovulate mice using standard procedures (PMSG hCG), followed by collection of reproductive tract after follicular stimulation alone (PMSG) or following ovulation (hCG). Ovarian folliculogenesis and ovulation rate will be determined in fixed tissues following return in order to determine fertility. Ovarian and uterine tissues will also be evaluated by hormonal and gene expression profiling using quantitative approaches (radioimmunoassays, western blots, digital droplet PCR). Comparisons will be made to contemporary vivarium and Rodent Research Hardware Transporter and Habitat housed animals maintained on earth. Supported by NNX15AB48G to JST.

Christenson, Lane↗
NASA NTRS2017

Studying the Effect of Radiation in the Context of Deep Space Travel

While it has been shown that decades of astronauts and cosmonauts can suffer from illnesses both during and after spaceflight, the underlying causes are still poorly understood, due in part to the fact that there are so many variables to consider when investigating the human immune system in a complex environment. Invertebrates have become popular models for studying human disease because they are cheap, highly amenable to experimental manipulation, and have innate immune systems with a high genetic similarity to humans. Fruit flies (Drosophila melanogaster) have been shown to experience a dramatic shift in immune gene expression following spaceflight, but are still able to fight off infections when exposed to bacteria. However, the common bacterial pathogen Serratia marcescens was shown to become more lethal to fruit flies after being cultured in space, suggesting that not only do we need to consider host changes in susceptibility, but also changes in the pathogen itself after spaceflight conditions. Being able to simulate spaceflight conditions in a controlled environment on the ground gives us the ability to not only evaluate the effects of microgravity on the host immune system, but also how the microorganisms that cause immune disorders are being affected by these drastic environmental shifts. In this study, I use a ground-based simulated microgravity environment to examine the genetic changes associated with increased S. marcescens virulence in order to understand how microgravity is affecting this pathogen, as well as how these genetic changes influence and interact with the host immune system. This study will provide us with more directed approaches to studying the effects of spaceflight on human beings, with the ultimate goal of being able to counteract immune dysfunction in future space exploration.

Bhattacharya, Sharmila↗
NASA NTRS2017

Skeletal Responses to Long-Duration Simulated Weightlessness in Rats

Damaging effects due to spaceflight and long-duration weightlessness are seen in the musculoskeletal system, specifically with regards to bone loss, bone resorption, and changes in overall bone structure. These adverse effects are all seen with indicators of oxidative stress and a variation in the levels of oxidative gene expression. Once gravity is restored, however, the recovery is slow and incomplete. Despite this, few reports have investigated the correlation between oxidative damage and general modifications within the bone. In this project, we will make use of a ground-based model of simulated weightlessness (hindlimb unloading, HU) in order to observe skeletal changes in response to induced microgravity due to changes in oxidative pressures. With this model we will analyze samples at 14-day and 90-day time points following HU for the determination of acute and chronic effects, each with corresponding controls. We hypothesize that simulated microgravity will lead to skeletal adaptations including time-dependent activation of pro-oxidative processes and pro-osteoclastogenic signals related to the progression, plateau, and recovery of the bone. Microcomputed tomography techniques will be utilized to measure skeletal changes in response to HU. With the results of this study, we hope to further the understanding of skeletal affects as a result of long-duration weightlessness and develop countermeasures to combat bone loss in spaceflight and osteoporosis on Earth.

hindlimb unloading↗
NASA NTRS2018

Stress-Induced Heat Shock Protein 40 and Immune Function in Altered Gravity

In space, astronauts are more susceptible to pathogens, viral reactivation and immunosuppression, which poses limits to their health and the mission. Interestingly, during space flight, stress-inducible heat shock proteins (HSP) are robustly induced, and the overexpression of HSPs have been implicated in immune dysregulation, therefore HSPs may be critically involved in regulating immune homeostasis. HSP40/DNAJ1 plays a major role in proper protein translation and folding. Its loss of function has been implicated in susceptibility to microbial infection, while its overexpression has been implicated in autoimmunity, collectively suggesting its complicated, but necessary, role in maintaining immunological function. To determine the role of HSP40 during stress-induced altered gravity conditions, wild-type and Hsp40 mutant Drosophila melanogaster were exposed to ground-based chronic hypergravity conditions, followed by quantitative PCR (qPCR) analysis of immune gene expression. In addition, larval hemocytes were collected to determine the functional output in response to E. coli bioparticle phagocytosis. Preliminary data indicates a required role for Hsp40 in strengthening immune function during stress-induced spaceflight in flies. In short, a critical need to evaluate the relationship between HSPs and immune suppression during space flight is necessary. Since space travel may become available to the general public in the not too distant future, and for the possibility of long-term space missions, a more comprehensive evaluation of the molecules responsible for immune dysfunction observed during space flight is required.

hypergravity↗
NASA NTRS2018

Effects of Simulated Microgravity on a Host-Pathogen System

While it has been shown that decades of astronauts and cosmonauts suffer from immune disorders both during and after spaceflight, the underlying causes are still poorly understood, due in part to the fact that there are so many variables to consider when investigating the human immune system in a complex environment. Invertebrates have become popular models for studying human disease because they are cheap, highly amenable to experimental manipulation, and have innate immune systems with a high genetic similarity to humans. Fruit flies (Drosophila melanogaster) have been shown to experience a dramatic shift in immune gene expression following spaceflight, but are still able to fight off infections when exposed to bacteria. Furthermore, a recent spaceflight mission showed that flies are more susceptible to infection following exposure to microgravity conditions, compared to ground-reared flies from the same population. Additionally, the common bacterial pathogen Serratia marcescens was shown to become more lethal to fruit flies (both space- and ground-reared) after being cultured in space, suggesting that not only do we need to consider host changes in susceptibility, but also changes in the pathogen itself after spaceflight conditions. Being able to simulate spaceflight conditions in a controlled environment on the ground gives us the ability to not only evaluate the effects of microgravity on the host immune system, but also how the microorganisms that cause immune disorders are being affected by these drastic environmental shifts. In this study, I use both spaceflight and ground-based (simulated microgravity) environments to examine the genetic changes associated with increased S. marcescens virulence in order to understand how microgravity is affecting this pathogen, as well as to evaluate how these genetic changes influence and interact with the host immune system. This study will provide us with more directed approaches to studying the effects of spaceflight on human beings, with the ultimate goal of being able to ameliorate human immune dysfunction in future space exploration.

Immunology↗
NASA NTRS2016

Integrating Large Scale Data Sets to Develop Predictive Hypotheses of Low-Dose Radiation-Induced Health Effects

Over one hundred years of radiation biology research has revealed much about the DNA damages induced by the deposition of energy from exposure to ionizing radiation and the subsequent cellular responses. However, there are still significant gaps in our understanding of how these might lead to detrimental health effects, particularly at low doses (100 mGy (milligray)). Recent advances in high throughput omics technologies enable interrogation of induced radiation effects at the genomic, proteomic and metabolomic levels. These include changes in gene expression, protein modifications, e.g., phosphorylation, acetylation, and methylation, and metabolic changes. We will discuss the integration of data obtained from multiple omics platforms to understand radiation dose, and dose rate effects in a complex human tissue model as a function of time. We will use as an example our results on the low dose responses in a 3D human skin model.

ionizing radiation↗
NASA NTRS2014

Drosophila Habitat Developed to Support Research on the International Space Station

The Fruit Fly Lab is a hardware suite being designed to support research on the International Space Station (ISS) for use by the entire Drosophila research community. A validation mission will launch and return on SpaceX-5 in late 2014, followed by Principal Investigator-lead science flights thereafter. Space flight experiments are selected via peer-reviewed proposals open to the Drosophila community. The cassettes (containers) that will house the Drosophila cultures were successfully used to conduct an immunity study on the Space Shuttle. Results showed that the innate immune system of Drosophila melanogaster was affected by space flight with a reduction in phagocytosis function of plasmatocytes, changes in antimicrobial peptides and other gene expression levels, as well as changes in development of the animals. Scientific research topics that are of interest to NASA will be presented. Each cassette used to house the Drosophila has a removable food tray that can be replaced to sustain the growth of the culture, or can be transferred to another cassette, along with embryos and burrowed larvae, enabling multi-generational studies. The cassette can be frozen in the Minus Eighty Laboratory Freezer for ISS to preserve samples until post-flight analysis, expanding the applications of the hardware. Utilization of a centrifuge allows for on-orbit 1g controls for microgravity experiments, as well as variable g-levels for lunar or Mars environment studies. The standard form factor used also allows for implementation of modular upgrades. An observation system, circadian rhythm lighting system, and fixation capability are upgrades currently in development for near-term implementation. This hardware suite, with its flight- proven design and ability to utilize existing on-board facilities, offers the whole Drosophila research community a platform to address several key areas of the National Research Councils decadal survey, supporting the utilization of ISS for science discovery.

Drosophila↗