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Many breakthroughs in biological research and translational advancements to the healthcare setting have been achieved through studying the response of biological systems to extreme environments. The spaceflight research platform is no exception to this rule, and provides a unique environment where researchers can explore fundamental questions into cellular and molecular response mechanisms that provide unique insight into human health and disease development. Indeed, since gravity has shaped the architecture of all biological systems on our planet, spaceflight provides the opportunity to see life in a new adaptational mode not seen before, in response to the reduced force of gravity. This allows researchers to study the effects of the microgravity environment and associated changes in mechanical forces on cell and tissue function, explore fundamental questions about human health and physiology, and advance our understanding of cellular and molecular processes in both normal and diseased cells that are not discernable using conventional experimental approaches.§§In an era that promotes the integrated study of biological systems with engineering and the physical sciences as the prevalent concept in contemporary scientific thinking, transition to the use of spaceflight as a next generation research platform represents a paradigm shift in how we observe life processes and study cellular and molecular responses to extreme conditions, and is on the leading edge of discoveries that have widespread implications for control of cell and tissue physiology. By incorporating the views of leading authors in the field, this book highlights landmark discoveries and advances in mammalian cellular and microbiology research in both true spaceflight and ground-based spaceflight analogue environments (the latter focused on NASA-designed rotating wall vessel bioreactor technology) for scientists and students alike who are interested in the influence of physical forces on cells, how this impacts their transition between normal homeostasis and disease progression, and basic mechanisms of their adaptation to low gravity environments. To provide a thorough understanding of this research, this book covers a broad range of topics including:§§ (i) a description of the physical forces interacting with cells in microgravity and microgravity analogue environments,§§ (ii) an example of how alterations in these cellular forces can impact human physiology, specifically immune function,§§ (iii) utilization of these environments to develop novel organotypic three-dimensional (3-D) tissue culture models as predictive human surrogates for organogenesis and disease research, and§§ (iv) the response of microorganisms to culture in these environments, with a focus on microbial pathogenesis and infectious disease.§§Taken together, this information reflects a critical step in preparation for long-duration human space exploration, advances our knowledge of basic biological processes and mechanisms important to understand the transition between normal function and disease progression, and provides novel insight into the mechanisms and treatment of various medical conditions here on Earth.§