After a series of discussions with NASA's Life Sciences Division, the committee agreed to undertake a comprehensive review of the status of research in the various fields of space life sciences and to develop a science strategy that could guide NASA in its long-term research and mission planning. This study was carried out over a 3-year period, and its objectives remained the same as those outlined in the report: Assessment of Programs in Space Biology and Medicine National Academy Press, Washington, D.
In addition to numerous expert speakers from NASA and academia, who were invited to give presentations at regular committee meetings, the CSBM used a variety of approaches to gather information for its task. Three workshops were organized by the committee, each focusing on a broad life sciences discipline, and both NASA and non-NASA investigators were invited to participate.
The committee also sent delegates to several international life sciences workshops organized by NASA and its international partners. Each workshop was directed at reviewing progress in a specific discipline and included participation by space life sciences investigators from around the world. Of course, the committee also reviewed both NASA source materials and the relevant literature, published and online, on flight- and ground-based research. Separate discipline panels, each chaired by a member of the CSBM, were developed to review and discuss the areas of space radiation and human behavioral studies.
These two groups were given responsibility for drafting the sections of this report representing their disciplines, although the final report is the responsibility of the committee as a whole. As originally planned, the recommendations and analysis developed by the Task Group on the Biological Effects of Space Radiation and published separately in 4 form the basis of Chapter 11 , "Radiation Hazards," in CSBM's new strategy for research.
Radiation Hazards to Crews of Interplanetary Missions: Biological Issues and Research Strategies. This report has been reviewed by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the National Research Council's NRC's Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the authors and the NRC in making the published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge.
The contents of the review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following individuals for their participation in the review of this report:.
Developmental Biology Research in Space
Although the individuals listed above have provided many constructive comments and suggestions, responsibility for the final content of this report rests solely with the authoring committee and the NRC. Gravity, Microgravity, and Weightlessness. Direct and Indirect Effects of Microgravity. Previous Cell Biological Research in Space. Mechanisms of Cellular Response to Mechanical Force. Cellular Response to Environmental Stress.
Development of Advanced Instrumentation and Methodologies. Progress in Developmental Biology. Major Issues in Space Developmental Biology. Complete Life Cycles in Microgravity. Development of the Vestibular System. Reasons for Studies on Space Horticulture. Role of Gravity in Plant Processes. Vestibulo-Ocular Reflexes and Oculomotor Control. Vestibular Processing During Microgravity.
Central Nervous System Reorganization. Bone Functions, Growth and Development, and Remodeling. Bone Growth and Development. Mechanical Effects on Bone Remodeling. Clinical Observations and Human Experimentation. Microgravity Effects on the Skeleton. Research Done on Muscle Biology. Previous Space- and Ground-based Research. Simple Deconditioning and Adaptation. Pathological Alteration and Metabolic Adaptation.
Contractile Physiology, Contractile Proteins, and Myofilaments. Preservation of Function During Atrophy. Reentry- and Reloading-induced Secondary Changes. Movements in Space and Upon Return to Earth. Increased Susceptibility to Structural Damage. Cellular and Molecular Mechanisms. Cardiovascular Physiology in Microgravity. Pulmonary Physiology in Microgravity.
Current Status of Research. Effects of Spaceflight on Humans. Energy Metabolism and Balance. Fluid and Electrolyte Balance.
NASA Selects 26 Space Biology Research Proposals | NASA
Hormonal Systems and Changes. Endocrine Aspects of Muscle Loss. Current Understanding of Biological Effects of Radiation. Effects Induced by Protons and Heavy Ions. Priority Research Recommendations and Strategies. Experimental Techniques and New Data Required. Ground- versus Space-based Research. Definition and Assessment of Behavior and Performance in Space.
Research in Analogue Environments. Integration of Research and Operations. Organizational Support of Research. Environmental Conditions Unique to Spaceflight. Circadian Rhythms and Sleep. The Psychophysiology of Emotion and Stress. Psychophysiological Measurement in Space.
Crew Tension and Conflict. Physiological and Psychological Effects of Spaceflight. Loss of Weight-bearing Bone and Muscle. Physiological Effects of Stress. Psychological and Social Issues. Mechanisms of Graviperception and Gravitropism in Plants. Mechanisms of Graviperception in Animals. Effects of Spaceflight on Reproduction and Development. Criteria for Space Research. Integration of Research Activities. Construction of the international space station, scheduled to start in late , ushers in a new era for laboratory sciences in space.
This is especially true for space life sciences, which include not only the use of low gravity as an experimental parameter to study fundamental biological processes but also the study of the serious physiological changes that occur in astronauts as they remain in space for increasingly longer missions. This book addresses both of these aspects and provides a comprehensive review of ground-based and space research in eleven disciplines, ranging from bone physiology to plant biology.
Fully evaluating the true physiological significance of many of the reported effects is often difficult. Moreover, our understanding of mechanisms responsible for these changes is still limited. In particular, which of these effects should be attributed to direct effects of gravity on cells, and in contrast, which are the result of indirect effects resulting from alterations of the cellular environment? The importance of providing adequate nutrient and gas exchange has been convincingly demonstrated by Musgrave and co-workers 31 for intact Arabidopsis plants in-flight; similar considerations would surely hold for cells in culture.
An alternative hypothesis 32 attributed decreased glucose utilization to a lack of a requirement for the maintenance of position of subcellular structures, or positional homeostasis. In addition, the induction of the cellular stress response by other perturbing factors in the environment including strong hypergravity and vibration levels during launch and reentry is undoubtedly important.
Finally, the potential for enhanced radiation damage must be considered 33 see Chapter 11 , although appropriate shielding and short-duration studies can minimize such effects. These and other problems are likely to be confounding variables that are difficult to evaluate by ground controls and that preclude unambiguous identification of microgravity per se as the agent responsible for a given effect. Nevertheless, the question of whether single cells might sense gravity directly and if so, how, has received theoretical consideration.
Some researchers have proposed that single normal-sized cells e. Examples have been proposed: Interaction of plasma membrane integrins with the extracellular matrix or substratum may transduce a reorganization of the intracellular cytoskeleton, with profound effects on cell behavior and gene expression; 36 inherent amplification and adaptation detection of relative changes, potentially over a wide range of input of cellular biochemical networks are being analyzed in ever greater detail.
In summary, experience from numerous previous studies, both in-flight and ground based, has highlighted certain pitfalls that can and must be avoided in the design and analysis of future experiments. Thus, the design of experiments in cell biology should evolve from the extensive and growing context of basic cell biological research. There is a strong current trend toward the investigation of cell biology at the level of molecular mechanism.
Similarly, space cell biology should emphasize the identification of molecular mechanisms by which cells and tissues respond to spaceflight conditions. A few well-chosen model systems should be used to facilitate comparisons among experiments and create a reliable baseline of data. Experiments should begin with extensive ground-based analyses of normal i. Growing consideration should be given to studies on cells in situ, using steadily improving techniques for the analysis in intact tissues and organisms of cellular physiology from initial gene expression to cell architecture e.
Finally, there have been difficulties in critically evaluating some studies in spaceflight that used cell culture techniques. To minimize these problems, experiments with cells in culture should be carefully evaluated before they are conducted, with thought given to their theoretical and practical justification, the availability of fully tested hardware, the capacity to carry out appropriate controls, adequate sample sizes, and the potential for repetition. The problem of the lack of sedimentation and fluid and gas convection in weightlessness must be considered.
Differences in the fragility inherent among various cell strains and types also should be noted in choosing and comparing model systems. Generally, single cell culture models should be analyzed in ground-based studies. As biomedical research as a whole moves toward the goal of understanding the molecular mechanisms underlying physiology, NASA-sponsored research over the next decade should focus on cellular and molecular mechanisms responsible for specific physiological phenomena in which microgravity or other stressful aspects of the space environment are significant.
In other words, the space environment should be a potentially significant variable. For example, mechanisms by which cells respond to mechanical forces such as shear and gravity, and those related to environmental stress, are areas of special interest and opportunity for continued NASA emphasis. See also the sections in this report on bone, muscle, cardiovascular physiology, immunology, and neuroendocrine and sensorimotor integration for additional focused discussions. Weight-bearing bone and skeletal muscle require the gravity-dependent mechanical force of compression on bone and contraction of muscle to maintain homeostasis of bone and muscle mass see Chapters 6 and 7.
Nevertheless, the molecular and cellular mechanisms whereby these tissues respond to modulate bone or muscle synthesis and resorption, turnover, and remodeling in response to gravitational forces are not well understood. These questions are central to space biology and medicine at the cellular level. Similar considerations hold for the investigation of other systems that respond directly to gravitational stimuli.
These include the cellular mechanisms within the vestibular system involved in gravity reception and transduction of gravitational signals into perception of spatial orientation; gravitational. General mechanisms of mechanoreception and pathways of signal transduction from mechanical stresses are therefore recommended as areas of special opportunity and relevance for NASA life sciences.
Many different cell types respond to various molecular and physical stimuli via a limited number of transduction pathways. Therefore, even though the final physiological effects may differ with stimulus and cell type, the probability is high that the tissue-specific response pathways to gravitational force will share common mechanistic features with other kinds of force-sensing pathways. Studies of mechanisms of cellular mechanoreception should include identification of the cellular receptor, investigation of possible changes in membrane and cytoskeletal architecture, and analysis of pathways of response, including signal transduction and resolution in time and space of possible ion transients.
Space is a stressful environment. Organisms have developed highly sophisticated mechanisms for coping with stress, not only at the organismic and physiological levels but also at the level of single cells.
The mechanisms by which cells perceive, respond, and adapt to various kinds of environmental stress are a major research emphasis in cell biology and are relevant to understanding the mechanisms of response to the space environment. Studies of cellular responses to environmental stresses encountered in spaceflight e. Conducting sophisticated cell biology experiments in space successfully will require the development of highly automated and miniaturized instrumentation and advanced methodologies, many of which will be equally useful for ground-based research.
The recommendations of a previous report that "dedicated microprocessors should be used for process control, data storage, or both, and rapid communication in real time with ground-based teams should be a goal" remain valid. NASA should work with the scientific community and industry to foster development of advanced instrumentation and methodologies for space-based studies at the cellular level.
National Academy Press, Washington, D. Current Protocols in Molecular Biology. The emergence of digital microscopy.
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Optical microscopy in physiological investigations. Present capabilities and future prospects. Antibodies in cell biology. Academic Press, San Diego. Is there a neural stem cell in the mammalian forebrain? Tissue culture in microgravity. Current Protocols in Protein Science, Vol. High resolution separation and analysis of biological macromolecules. Extension of life-span by introduction of telomerase into normal human cells.
Protein kinases and phosphatases: The yin and yang of protein phosphorylation and signaling. The architectural basis of cellular mechanotransduction. Protein sorting by transport vesicles. Functional rafts in cell membranes. A model for central synaptic junctional complex formation based on the differential adhesive specificities of the cadherins.
Protein molecules as computational elements in living cells. Summary of biological spaceflight experiments with cells. Gravitational and space biology at the cellular level. Activation of lymphocytes and other mammalian cells in microgravity. Biology under microgravity conditions in Spacelab IML Possible mechanisms of indirect gravity sensing by cells.
Cell functions and biological processing in a microgravity environment. Modification of reproductive development in Arabidopsis thaliana under spaceflight conditions. Gravity and positional homeostasis of the cell. National Aeronautics and Space Administration. Cell and Molecular Biology in Context. Theoretical studies on living systems in the absence of mechanical stress.
Complex oscillations in simple neural systems. Molecular chaperons in cellular protein folding. Make it or break it: The role of ubiquitin-dependent proteolysis in cellular regulation. Assessment of Programs in Space Biology and Medicine National Academy Press, Washington D.