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At least 127 records · Page 7

NASA GeneLab Space Omics Database: Expanding from Space to Ionizing Radiation Data on the Ground

NASA GeneLab is an open-access repository for omics datasets generated by biological experiments conducted in space or ground experiments relevant to spaceflight (e.g. simulated cosmic radiation, simulated microgravity, bed rest studies). The GeneLab Data Systems (GLDS) version 4.0 will be available on October 1st 2019, and will provide a state-of-the-art bioinformatics platform for the space biology and radiation communities to upload their data into an omics data commons, to process their data with vetted standard workflows and to compare with existing analyses. Started in 2015 as a repository designed to archive omics data from space experiments, GeneLab has expanded its scope to all ionizing radiation omics experiments conducted on the ground and has put considerable effort in providing carefully characterized radiation metadata on all datasets. GeneLab is also providing processed data derived from the raw data covering a large spectrum of omics (genome, epigenome, transcriptome, epitranscriptome, proteome, metabolome) to help users explore important questions: 1) Which genes or proteins are expressed differently in space for various living organisms? 2) What specific DNA mutations or epigenetic changes happen in space or after exposure to ionizing radiation? and 3) How does genetics affect these responses? Processed data available on GeneLab are derived by standard data analysis workflows vetted by hundreds of scientists who volunteered to join one of the four GeneLab Analysis Working Groups (Animal AWG, Plant AWG, Microbe AWG, Multi-Omics AWG). In this presentation, we will discuss how to bridge the gap between irradiation studies performed on earth and biological experiments conducted in space since the early 1990's. We will discuss how radiation dosimetry was estimated for datasets derived from samples collected during the Space Shuttle era on the International Space Station and on other orbiting platforms. Finally, we will address future strategies regarding dose monitoring in future missions into space, inter-agency efforts to unify data under one umbrella, and knowledge dissemination across the radiation research community and the space biology community.

open-science↗

Maximizing Spaceflight Biological Data with Omics Analytics: The NASA GeneLab Database

NASA’s GeneLab includes an open-access repository of some 250+ omics datasets generated by biological experiments relevant to spaceflight including simulated cosmic radiation and microgravity. In order to maximize the intelligibility of these data, particularly for users with limited bioinformatics background, GeneLab has become a knowledgebase platform converting raw genetic and proteomic signatures found in flight samples into biological and physiological meanings. A large community of more than 100 scientists has rallied behind GeneLab and organized into four Analysis Working Groups (AWGs: Animal, Plant, Microbe, and Multi-Omics). Together, the AWGs have gained scientific recognition worldwide by establishing a consortium in charge of adopting new complex standards for data analysis workflows and omics sample processing in a rapidly evolving field. We will demonstrate the usage of the repository with smart search capability, an online controlled-access toolshed "Galaxy" to process user data with vetted standard workflows, a workspace for data sharing and a data submission portal with ontology control for better metadata curation. The GeneLab visualization portal will also be demonstrated, showing how anyone without formal training in bioinformatics can now browse the space biology omics data to discover new biology and potential solutions to improve life in space.

Sylvain Vincent Costes↗

BioNutrients-1: Development of an On-Demand Nutrient Production System for Long-Duration Missions

Future long-duration missions beyond low-Earth orbit will require advances in food technologies to address the documented problem of degradation of vitamins and nutrients in supplied foods stored long-term. To begin to address the issue of nutrient degradation, we are developing and flight-testing a platform biomanufacturing technology for in situ production of target nutrients. This technology is being tested over a five-year duration on the International Space Station (ISS). As part of the BioNutrients-1 project we have developed an on-demand system for the production of two carotenoids, β-carotene and zeaxanthin, by genetically engineering distinct strains of Saccharomyces cerevisiae, more commonly known as baker’s yeast. The on-orbit nutrient production packs contain a desiccated yeast strain and edible growth substrate. Once hydrated, the contents of the production packs are intended to grow and produce a desired amount of ready-to-consume nutrients. In this current version the production packs will not be consumed and future missions will require an inactivation of microorganisms before consumption. In addition to the on-orbit hydration of the production packs a series of valuable microorganisms are currently being stored in stasis packs on the ISS including probiotics organisms, bacterial strains used in yogurt production, and organisms with potential use for future biomanufacturing. Analysis of returned ISS stasis packs and ground controls will include multi-omics studies and provide insight into long-term survival of organisms stored in a space environment. Both stasis packs and hydrated production packs will be intermittently returned to Earth for analysis. Preliminary data from long-term storage studies of stasis packs stored on the ISS for 47 days versus their ground control counterparts have shown no significant difference in viability. Currently no production packs have been processed.

Yeast↗

GeneLab: The NASA System Biology Platform for Space Omics Repository, Analysis and Visualization

NASA’s GeneLab includes an open-access repository of some 250+ omics datasets generated by biological experiments relevant to spaceflight including simulated cosmic radiation and microgravity. In order to maximize the intelligibility of these data, particularly for users with limited bioinformatics background, GeneLab has become a knowledgebase platform converting raw genetic and proteomic signatures found in flight samples into biological and physiological meanings. A large community of more than 100 scientists has rallied behind GeneLab and organized into four Analysis Working Groups (AWGs: Animal, Plant, Microbe, and Multi-Omics). Together, the AWGs have gained scientific recognition worldwide by establishing a consortium in charge of adopting new complex standards for data analysis workflows and omics sample processing in a rapidly evolving field. We will demonstrate the usage of the repository with smart search capability, an online controlled-access toolshed "Galaxy" to process user data with vetted standard workflows, a workspace for data sharing and a data submission portal with ontology control for better metadata curation. The GeneLab visualization portal will also be demonstrated, showing how anyone without formal training in bioinformatics can now browse the space biology omics data to discover new biology and potential solutions to improve life in space.

GeneLab↗

Knowledge Network Embedding of Transcriptomic Data From Spaceflown Mice Uncovers Signs and Symptoms Associated With Terrestrial Diseases

There has long been an interest in understanding how the hazards from spaceflight may trigger or exacerbate human diseases. With the goal of advancing our knowledge on physiological changes during space travel, NASA GeneLab provides an open-source repository of multi-omics data from real and simulated spaceflight studies. Alone, this data enables identification of biological changes during spaceflight, but cannot infer how that may impact an astronaut at the phenotypic level. To bridge this gap, SPOKE, a heterogeneous knowledge graph connecting biological and clinical data from over 30 databases, was used in combination with GeneLab transcriptomic data from six studies. This integration identified critical symptoms and physiological changes incurred during spaceflight.

spaceflight↗

NASA GeneLab: Open Science for Life in Space

NASA’s GeneLab helps scientists understand how the fundamental building blocks of life – DNA, RNA, proteins, and metabolites – change from exposure to the space environment including microgravity and cosmic radiation exposure. GeneLab does so by providing fully coordinated epigenomics, genomics, transcriptomics, proteomics, and metabolomics data (collectively known as omics data) alongside essential metadata describing each spaceflight and space-relevant experiment. The open-access GeneLab repository currently consists of over 300 omics datasets generated by biological experiments, involving various model organisms, that are relevant to spaceflight. In order to maximize the intelligibility of these data, particularly for users with limited bioinformatics knowledge, GeneLab has started processing and analyzing these datasets to generate differential gene expression data and identify biological and physiological pathways that are dysregulated as a result of spaceflight. To aide GeneLab’s efforts to harmonize and democratize space-relevant omics data, over 130 scientists have joined one of four GeneLab Analysis Working Groups (Animal AWG, Plant AWG, Microbe AWG, Multi-Omics AWG) and together helped develop and adopted standard data analysis workflows for all data types available in GeneLab. Currently, the GeneLab Data System includes a data repository with federated search capability, an online controlled-access toolshed powered by "Galaxy" for users to process data with vetted standard workflows, a workspace for data sharing, a data submission portal, and the ability to browse and visualize transcriptomics processed data. The user interface was designed to be accessible to a broad variety of users, including high school and college students who can use it to learn about omics data analysis and space biology. The visualization portal enhances GeneLab’s ability to democratize omics data by removing the need for bioinformatics expertise to interpret transcriptomics data hosted on GeneLab. This presentation will provide an over-view of NASA’s GeneLab including how to navigate the GeneLab Data System and will conclude by providing resources for opportunities to work with GeneLab and NASA at large.

Amanda M Saravia-Butler↗

GL4U: Training the next generation of bioinformaticians, one omics datatype at a time

Spaceflight modifies gene expression in every organism examined to date, including humans. Understanding how these gene expression changes affect physiology is crucial for the development of countermeasures to enable long-duration manned missions. NASA’s GeneLab project provides researchers open access to multi-omics data, including genetic and gene expression data, from spaceflight experiments that can be mined to understand the effects of spaceflight on biological systems. To ensure new knowledge generation through data re-use, it is important to maximize the number of scientists who utilize GeneLab data. Training students on the GeneLab platform is the best way to create long-term adopters of this NASA database and its tools. Turning students into future instructors and advocates will also accelerate the dissemination of these data and tools to the broader scientific community. Therefore, in collaboration with the GeneLab Educational Working Group (EWG), GeneLab has created GeneLab for Colleges and Universities (GL4U). GL4U provides space biology-relevant training in bioinformatics to the next generation of scientists through direct and indirect approaches. The GeneLab team plans to host two annual data processing bootcamps, one for college-level students (direct) and one for college educators (indirect – training of trainers), in which participants learn to analyze GeneLab’s space-relevant omics data. During the bootcamp, educators will receive materials and training to enable them to run the bootcamp at their home institutions or alternatively to adapt the content to implement within existing courses, thereby extending the reach of this initiative. The GL4U direct training pilot program was conducted in June 2021 in collaboration with USRA and San Jose State University (SJSU). During the pilot, SJSU students participated in a week-long bootcamp consisting of space biology-specific lectures and hands-on instruction using Jupyter Notebooks to analyze RNA sequence data. This pilot demonstrates the capacity of GL4U for training young scientists and encouraging data re-use.

Jonathan Matthew Galazka↗

Mitochondria Dysfunction Central in Driving Health Risks Associated with Spaceflight

Background: Determining the biological impact of spaceflight through novel approaches is essential to reduce the health risks to astronauts for long-term space missions. The current established health risks due to spaceflight are only reflecting known symptomatic and physiologic responses and do not reflect early onset of other potential diseases. There are many unknown variables which still need to be identified to fully understand the health impacts due to the environmental factors in space. Materials and Methods: One method to uncover potential novel biological mechanisms responsible for health risks in astronauts is by utilizing NASA’s GeneLab platform (genelab.nasa.gov). GeneLab is public repository that hosts multiple omics datasets generated from space biology experiments that include experiments flown in space, simulated cosmic radiation experiments, and simulated microgravity experiments. This presentation will provide an example of analysis and novel hypothesis generation that is being produced with GeneLab datasets. A comprehensive multi-omics approach was implemented correlating transcriptomics, proteomics, metabolomics, and methylation analysis. Results: We found that cells have stronger overall biological response than the tissues to spaceflight, with mitochondrial activity and innate immunity pathways being heavily impacted. NASA Twin Study results are consistent with a specific alteration in mitochondrial ATP production. Our results indicate that the space environment can directly induce mitochondrial damage, with mitochondrial dysfunctions being a cause for chronic inflammation and both being involved in the development of metabolic disorders that cause changes in lipid metabolism. We also found biological changes occurring during spaceflight with cell cycle, circadian rhythm and olfactory activity pathways can also influence and be influenced by alterations on mitochondrial activity

Afshin Beheshti↗

GeneLab: Current and Future Omics Data Integration Between Space Biology and HRP

For the past five years, the Biological and Physical Sciences Division has pioneered Open Science in Space Biology by funding the NASA GeneLab project. Along with the Ames Life Sciences Data Archive, GeneLab has quickly become the world leader in archiving and scientifically curating spaceflight and spaceflight relevant multi-omics data. Specifically, the GeneLab Data System has become a full enterprise solution providing advanced mining capabilities, several application programming interfaces for data federation and machine learning approaches, and delivering to the world an analytical and visualization platform which has enabled collaboration within the scientific community. Over the past three years, large meta-analysis and modeling studies have been published by the GeneLab Analysis Working Groups (AWGs), which are comprised of ~200 volunteer scientists. One natural extension of GeneLab data reuse has recently turned towards linking animal data with human data, which is the next necessary step to further validate animal models for inferring biological risks to humans conducting LEO, lunar or Martian missions. As such, data from the Human Research Program are an essential component of GeneLab and ALSDA. At the moment, simulated space radiation experiments conducted at Brookhaven National Laboratory make the most of HRP GeneLab data, and the scientific community has been eager to also link their animal spaceflight results to actual Astronaut data and human analog data. We will discuss further the current status of knowledge and future approaches to accelerate our basics understanding of the impact of space stressors on humans using latest omics technology.

omics↗

Open Science for Life in Space: Data Sharing and Tools for Knowledge Discovery

The next era in human space exploration is rapidly approaching and will require the use of countermeasures to deep space health hazards. The development of countermeasures (or, the re-purposing of existing agents) will be highly dependent on our understanding of basic biological responses to space stressors (e.g. ionizing radiation, altered gravitational fields, altered day-night cycles, confinement, isolation, hostile-closed environments, distance-duration from Earth, exposure to celestial regolith, etc.). The fast-growing array of space biological data, which in the past was simply archived after minimal analysis, holds great potential if it can be reorganized and formatted for Open Science. Organizing the data for such analysis is a challenge because of its diverse nature (molecular, cellular, tissue, imaging, whole organism and behavior). We will discuss here several strategies that NASA’s Biological and Physical Science Division has put in place to maximize the return on investment for spaceflight bioscience data. Open Science, as a scientific philosophy, is the concept that the more people who have access to the data, the more knowledge will be gained from it. This guiding principle led NASA to develop GeneLab in 2015. GeneLab houses spaceflight and relevant ground-based multi-omics data, and has grown to ~400 transcriptomic, proteomic, metabolomic and epigenomic datasets from plant, rodent, small animal, and microbial space experiments. GeneLab provides users with various tools for data analysis and a visualization portal that allows users to interact with gene expression data from space-related ‘omics experiments. Open Science is also about building scientific communities, and with this spirit in mind, GeneLab has spawned several Analysis Working Groups (AWGs), comprised of more than 200 volunteer scientists. The AWGs initially provided feedback on the processing pipeline and metadata ‘omics standards for GeneLab. Over the last few years, they have become a community-driven science enterprise, engaging in large meta-analysis of GeneLab datasets, resulting in 10 publications (beyond the originally submitted research). Overall, the Open Science nature of GeneLab has resulted in a high degree of data re-use, resulting in 38 additional publications derived from the original 67 publication over the past four years. The enormous success and knowledge gained from GeneLab has led to a collection of sister NASA “Open Science Data Repositories (OSDR)” and research support groups. These include the NASA Ames Life Sciences Data Archive (ALSDA), the NASA Biological Institutional Scientific Collection (NBISC), and the Biospecimen Sharing Program (BSP). All are adopting the GeneLab data architecture system to maximize open-access, find-ability, accessibility, interoperability, and reusability (FAIR). ALSDA collects and curates phenotypic-physiological bioimaging-behavioral data from space and space-relevant non-human experiments, oftentimes coming from the same omics-associated experimental datasets found in GeneLab. Since 2021, a community of ~100 researchers have rallied around ALSDA, to provide feedback in a new ALSDA AWG focused on phenotypic-physiological investigation-sample-assay metadata standards (e.g., Micro-Computed Tomography, Light/Fluorescence Microscopy, Western Blot, Flow Cytometry, Novel Object Recognition, Elevated Plus Maze, etc. of ~50 assays collected). These standards are part of a new single point-of-entry data submission portal for all non-human Space Biology and Human Research Program principal investigators, to submit, curate, and share their research data. With open-access space biological data now collected and curated together with rich metadata, and with the potential for linkage to “big data” from the international biological and medical communities (NIH, EBI, etc.), the artificial intelligence and machine learning (AI/ML) era has started for Space Biology. Several other talks will cover these topics in this conference.

life sciences↗

Open Science for Life in Space: Data Sharing and Tools for Knowledge Discovery

The next era in human space exploration is rapidly approaching and will require the use of countermeasures to deep space health hazards. The development of countermeasures (or, there-purposing of existing agents) will be highly dependent on our understanding of basic biological responses to space stressors (e.g. ionizing radiation, altered gravitational fields, altered day-night cycles, confinement, isolation, hostile-closed environments, distance-duration from Earth, exposure to celestial regolith, etc.). The fast-growing array of space biological data, which in the past was simply archived after minimal analysis, holds great potential if it can be reorganized and formatted for Open Science. Organizing the data for such analysis is a challenge because of its diverse nature (molecular, cellular, tissue, imaging, whole organism and behavior). We will discuss here several strategies that NASA's Biological and Physical Science Division has put in place to maximize the return on investment for spaceflight bioscience data. Open Science, as a scientific philosophy, is the concept that the more people who have access to the data, the more knowledge will be gained from it. This guiding principle led NASA to develop GeneLab in 2015. GeneLab houses spaceflight and relevant ground-based multi-omics data, and has grown to ~400 transcriptomatic, proteomic, metabolomic and epigenomic datasets from plant, rodent, small animal, and microbial space experiments. GeneLab provides users with various tools for data analysis and a visualization portal that allows users to interact with gene expression data from space-related 'omics experiments. Open Science is also about building scientific communities, and with this spirit in mind, GeneLab has spawned several Analysis Working Groups (AWGs), comprised of more than 200 volunteer scientists. The AWGs initially provided feedback on the processing pipeline and metadata 'omics standards for GeneLab. Over the last few years, they have become a community-driven science enterprise, engaging in large meta-analysis of GeneLab datasets, resulting in 10 publications (beyond the originally submitted research). Overall, the Open Science nature of GeneLab has resulted in a high degree of data-use, resulting in 40 enabled publications by open data. The enormous success and knowledge gained from GeneLab has led to a collection of sister NASA "Open Science Data Repositories (OSDR)" and research support groups. These include the NASA Ames Life Sciences Data Archive (ALSDA), the NASA Biological Institutional Scientific Collection (NBISC), and the Biospecimen Sharing Program (BSP). All are adopting the GeneLab data architecture system to maximize open-access, find-ability, accessibility, interoperability, and reusability (FAIR). ALSDA collects and curates phenotypic-physiological bioimaging-behavioral data from space and space-relevant non-human experiments, oftentimes coming from the same omics-associated experimental datasets found in GeneLab. Since 2021, a community of ~100 researchers have rallied around ALSDA, to provide feedback in a new ALSDA AWG focused on phenotypic-physiological investigation-sample-assay metadata standards (e.g., Micro-Computed Tomography, Light/Flourescence Microscopy, Western Blot, Flow Cytometry, Novel Object Recognition, Elevated Plus Maze, etc. of ~50 assays collected). These standards are part of a new single point-of-entry data submission portal for all non-human Space Biology and Human Research Program principal investigators, to submit, curate, and share their research data. With open-access space biological data now collected and curated together with rich metadata, and with the potential for linkage to "big data" from the international biological and medical communities (NIH, EBI, etc.), the artificial intelligence and machine learning (AI/ML) era has started for Space Biology.

omics↗

GL4U: Bioinformatics training for students and educators using space omics data

NASA’s GeneLab project provides researchers open access to space-relevant experiment multi-omics data that can be mined to understand the effects of spaceflight on biological systems. To maximize the number of scientists who understand and utilize GeneLab data and data processing pipelines, GeneLab has created GeneLab for Colleges and Universities (GL4U). GL4U provides space biology-relevant training in bioinformatics to the next generation of scientists through direct and indirect approaches. The GeneLab team plans to host two annual data processing bootcamps, one for college-level students (direct) and one for college educators (indirect – training of trainers), in which participants learn to analyze GeneLab’s space-relevant omics data. The GL4U direct training pilot program was conducted in June 2021. During the pilot, students participated in a week-long bootcamp consisting of space biology-specific lectures and hands-on instruction using Jupyter Notebooks to analyze RNA sequence data. This pilot demonstrated the capacity of GL4U for training young scientists and encouraging data re-use. During the educator pilot, scheduled for June 2022, educators will receive materials and training to enable them to run the bootcamp at their home institutions or alternatively to adapt the content to implement within existing courses, thereby extending the reach of this initiative.

Amanda Marie Saravia-butler↗

Open Science for Life in Space: Bioimaging, Data Sharing, and Tools for Knowledge Discovery

Precious space-flown biological experiments have both multi-omic and phenotypic data which NASA strives to make maximally open access for reuse. Currently a number of these space-relevant bioimaging datasets are being reused for AI/ML approaches. NASA Ames Life Science Data Archive and NASA GeneLab are working to make all current and future bioimaging data even more accessible and reusable. Standards for collection and curation are being implemented to enable scientists worldwide access to these data for further discovery and use.

data science↗

Open Science for Life in Space: Data Sharing and Tools for Knowledge Discovery

The fast-growing array of space biological data, which in the past was simply archived after minimal analysis, holds great potential if it can be reorganized and formatted for Open Science. Organizing the data for such analysis is a challenge because of its diverse nature (molecular, cellular, tissue, whole organism, behavior; tabular, imagery). Open Science is the concept that the more people have access to scientifically curated data, the more knowledge will be gained. This led NASA to start the development of GeneLab in 2015. GeneLab houses spaceflight and space-analog multi-omics datasets from plant, rodent, small animal, and microbial experiments. The success and knowledge gained from GeneLab led to a new alliance of NASA “Open Science Data Repositories” (OSDR), which include the Ames Life Sciences Data Archive (ALSDA) and the NASA Biological Institutional Scientific Collection (NBISC). Both are adopting the GeneLab data system, so data are more findable, accessible, interoperable, and reusable (FAIR). OSDR systems provide users the ability to upload, download, search, share, analyze, and visualize. Open Science also needs strong confidence in the data, which is gained through building science communities. With ~400 current members, GeneLab and ALSDA formed Analysis Working Groups (AWGs) to provide feedback on processing pipelines, metadata curation standards (for ‘omics and phenotypic-physiological-behavioral assays), and to collaborate in effectively reusing data. The AWG also led to the development of the Radiation Biology Ontology (RBO), ensuring radiation metadata are efficiently captured, connected, and interoperable. Feedback from the AWG provided design input toward the new single point-of-entry data submission portal for all investigators to submit, curate, and share their research data. Space biological data is now maximally open access, collected-curated with rich metadata, and formatted for interoperability to enable systems biology, meta-analysis, knowledge graphs, machine learning, modeling, and other reuse approaches. With potential for further federation of OSDR for data mining with traditional biological and medical databases (NIH, NCI, EBI, etc.), a new era for space biology has begun to support the knowledge discovery necessary for Lunar and Martian missions.

Ryan T Scott↗

GL4U: Using Space Omics Data to Provide Bioinformatics Training for Students and Educators

NASA’s GeneLab project provides researchers open access to space-relevant experiment multi-omics data that can be mined to understand the effects of spaceflight on biological systems. To maximize the number of scientists who understand and utilize GeneLab data and data processing pipelines, GeneLab has created GeneLab for Colleges and Universities (GL4U). GL4U provides space biology-relevant training in bioinformatics to the next generation of scientists through direct and indirect approaches. The GeneLab team plans to host two annual data processing bootcamps, one for college-level students (direct) and one for college educators (indirect – training of trainers), in which participants learn to analyze GeneLab’s space-relevant omics data. The GL4U direct training pilot program was conducted in June 2021. During the pilot, students participated in a week-long bootcamp consisting of space biology-specific lectures and hands-on instruction using Jupyter Notebooks to analyze RNA sequence data. This pilot demonstrated the capacity of GL4U for training young scientists and encouraging data re-use. In June 2022, GL4U partnered with Jet Propulsion Laboratory’s (JPL) Planetary Protection Center of Excellence to conduct the indirect training pilot program by training educators at historically black colleges and universities (HBCUs) and minority serving institutions (MSIs). During the educator pilot, participants received materials, training, and will be provided the necessary compute resources to enable them to run the bootcamp at their home institutions or alternatively to adapt the content to implement within existing courses, thereby extending the reach of this initiative. The GL4U training program provides undergraduate students from underrepresented groups the opportunity to learn about NASA and Space Biology, and to enhance their career prospects by gaining hands-on experience analyzing omics data, a skillset that is highly applicable and marketable in the life sciences. Pre- and post-bootcamp surveys were completed by all participants and show the overwhelming success of the bootcamps.

Amanda M. Saravia-Butler↗

GL4U: Bioinformatics Training for Students and Educators Using Space Omics Data

NASA’s GeneLab project provides researchers open access to space-relevant experiment multi-omics data that can be mined to understand the effects of spaceflight on biological systems. To maximize the number of scientists who understand and utilize GeneLab data and data processing pipelines, GeneLab has created GeneLab for Colleges and Universities (GL4U). GL4U provides space biology-relevant training in bioinformatics to the next generation of scientists through direct and indirect approaches. The GeneLab team plans to host two annual data processing bootcamps, one for college-level students (direct) and one for college educators (indirect – training of trainers), in which participants learn to analyze GeneLab’s space-relevant omics data. The GL4U direct training pilot program was conducted in June 2021. During the pilot, students participated in a week-long bootcamp consisting of space biology-specific lectures and hands-on instruction using Jupyter Notebooks to analyze RNA sequence data. This pilot demonstrated the capacity of GL4U for training young scientists and encouraging data re-use. During the educator pilot, scheduled for June 2022, educators will receive materials and training to enable them to run the bootcamp at their home institutions or alternatively to adapt the content to implement within existing courses, thereby extending the reach of this initiative.

Amanda Marie Saravia-butler↗

Neurovascular effects of simulated space radiation

A major health risk for human deep space exploration is central nervous system (CNS) damage by ionizing radiation. Simulated galactic cosmic rays or their components, especially high-linear energy transfer particles such as 56Fe ions, have been shown to cause CNS damage, neuroinflammation and cognitive dysfunction in rodent models, but their effects on human CNS remain to be investigated. CNS damage from any insult, including ionizing radiation, is partially mediated by the blood-brain barrier (BBB), which regulates interactions between CNS and the rest of the body. Astrocytes are major cellular regulators of BBB permeability and also modulate neuroinflammation and neurodegeneration. However, BBB and astrocyte functions in regulating CNS responses to space radiation remain little investigated, especially in human organ analogs. Therefore, we developed and utilized a high-throughput 3D human neurovascular organ-on-a-chip model, seeded with induced pluripotent stem cell-derived cells. The effects of time course, ionizing radiation dose and dose rate were mapped by exposing the model to either acute, high dose rate radiation with simulated galactic cosmic rays or 600 MeV/n 56Fe particles, or protracted, low dose rate gamma radiation using a 57Co sealed source setup. We investigated BBB permeability, oxidative stress, cellular damage and secreted factors over the time period between 24 hours – 2 weeks after 0.1 – 0.8 Gy irradiation. We observed that ionizing radiation exposure increased BBB permeability, caused oxidative stress, damaged endothelial cells and altered expression of inflammatory cytokines with a subset of outcomes dependent on ionizing radiation dose rate. Furthermore, our results indicated that astrocyte functions were primarily deleterious at early time points and protective later after irradiation, resembling CNS responses to injury in vivo. Our findings in organ models were complemented by studies on true spaceflight using mouse spatial and single cell multi-omics, which similarly indicated spaceflight-mediated changes in astrocyte functions. In summary, our study evaluates the regulation of neurovascular responses to simulated space radiation, suggesting astrocytes as targets for countermeasures to mitigate CNS damage in deep space exploration.

Radiation↗

Ampk alpha2 T172 activation dictates exercise performance and energy transduction in skeletal muscle

Adenosine 5′-monophosphate–activated protein kinase (AMPK) is an energetic sensor for metabolic regulation and integration. Here, we used CRISPR-Cas9 to generate nonactivatable Ampkα knock-in (KI) mice with mutation of threonine-172 phosphorylation site to alanine (T172A), circumventing the limitations of previous genetic interventions that disrupt the protein stoichiometry. KI mice of Ampkα2, but not Ampkα1, demonstrated phenotypic changes with increased fat-to-lean mass, impaired endurance exercise capacity, and diminished mitochondrial maximal respiration and conductance in skeletal muscle. Integrated temporal multiomics analysis (proteomics/phosphoproteomics/metabolomics) in skeletal muscle at rest and during exercise establishes a pleiotropic yet imperative role of Ampkα2 T172 activation for glycolytic and oxidative metabolism, mitochondrial respiration, and contractile function. There is a substantial overlap of skeletal muscle proteomic changes in Ampkα2 T172A KI mice with that of patients with type 2 diabetes. Our findings suggest that Ampkα2 T172 activation is critical for exercise performance and energy transduction in skeletal muscle and may serve as a therapeutic target for type 2 diabetes.

Bioenergetics↗