Future Biotechnology Research on the International Space Station (2000) / Chapter Skim
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1 Background and Scientific Scope of NASA Programs
1 Background and Scientific Scope of NASA Programs
Pages 10-22
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From page 10... ...
The protein crystal growth work focuses on using microgravity to produce higher quality macromolecular crystals for structure determination and on improving understanding of the crystal growth process. The cell science work focuses on basic research that contributes to understanding how the microgravity environment affects the fundamental behavior of cells, particularly in relation to tissue formation and the effects of space exploration on living organisms.
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From page 11... ...
, studies of defect formation during protein crystal growth and the effects of these defects on diffraction resolution (Dobrianov et al., 1998, 1999) , and analyses of predictors for protein crystallization using light-scattering measurements (Kao et al., 1998; Ansari et al., 1997~.1 These studies of the crystallization process have occasionally included flight components (McPherson et al., 1999~.
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From page 12... ...
Goals and History of the NASA Protein Crystal Growth Effort The current goals of the protein crystal growth efforts funded by NASA' s Microgravity Research Division are as follows: · Understanding the fundamental factors influencing macromolecular nucleation and growth; · Elucidating which factors may benefit crystal growth in the microgravity environment; · Growing significantly improved crystals in microgravity for structure determinations; · Determining the potential of microgravity to solve more complex and challenging crystallization problems, such as integral membrane proteins, glycoproteins, and lipoproteins; and · Developing technologies and methodologies such as automation and monitoring equipment that would improve the crystallization process on Earth as well as in space. The program began with exploratory efforts to grow macromolecular crystals in space in 1985.
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From page 13... ...
Despite the lack of impact of microgravity research on structural biology up to now, there is reason to believe that the potential exists for crystallization in the microgravity environment to contribute to future advances in structure determination. All research on protein crystallization in space so far has been done under suboptimal conditions.
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From page 14... ...
While the proteins in these experiments are not in themselves necessarily of great biological significance, the studies are important because of what they indicate about the potential benefits of crystal growth in space. Lysozyme, a workhorse in the field of protein crystal growth, yields crystals in space that have much better properties than those of crystals grown on Earth.
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From page 15... ...
. However, I'm not in a position to untangle all the factors and just don't have the data to say how much of the improvement was due to each of the factors." Potential Areas of Future Impact There is now a certain amount of evidence that crystal growth in a microgravity environment can have beneficial effects on the size and intrinsic order of macromolecular crystals.
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From page 16... ...
This makes it very difficult to obtain membrane protein crystals that diffract to high resolution, so membrane proteins are attractive targets for investigation in microgravity environments. Another general class of proteins yielding crystals that diffract very poorly are those that form transient complexes during dynamic events, such as during cellular signaling.
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From page 17... ...
The benefits that structural biologists will realize as their use of the space shuttle on an ad hoc basis is replaced by the deployment of a dedicated protein crystal growth facility on the ISS can be seen as parallel to the benefits they realized when they started using synchrotron facilities dedicated to the production of X rays (see Box 1.1~. For microgravity crystallization, the transition to a much more predictable and ordered regime on the ISS will have a maximum impact on modern biology if the projects chosen for experiments are ones that require improved crystallization to achieve significant scientific breakthroughs.
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From page 18... ...
About a decade ago, 12 of the largest pharmaceutical companies doing macromolecular structure research in the United States formed a consortium to build beam lines at the Advanced Photon Source.2 To date these companies have invested approximately $10 million in what appears to be a very successful venture. CELL SCIENCE Goals and Potential Impacts of the NASA Cell Science Effort The mission of the cell science program in NASA' s Microgravity Research Division is to obtain new knowledge and increase the understanding of how low gravity influences fundamental cell biology with respect to tissue formation and space exploration.
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From page 19... ...
More specific areas of impact might include the use of bioreactors for efficient high-fidelity production of complex proteins requiring significant post-translational processing; the propagation of parasites for evaluation of function; the propagation of tumor tissue for evaluation of responses to therapeutic options; the miniaturization of analytical equipment such as flow cytometers, mass spectrometers, and sensing systems; a better understanding of gene expression within the three-dimensional context of cell and tissue architecture; and an appreciation for the consequences of modified gravitational forces during launch, sustained periods in space, and reentry. Because many aspects of cell behavior and tissue growth under low gravity conditions are not well understood, the basic cell science research carried out on the ISS will increase the amount of information available to the community.
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From page 20... ...
With the increased availability of research opportunities on the ISS and the new hardware developed specifically for this platform, further investigation of these processes may clarify how cells behave in the microgravity environment. For example, a deeper comprehension could be sought about the mechanisms behind the observed effects of microgravity on cells relevant to human physiology (e.g., muscle, bone, balance, circulation)
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From page 21... ...
Efforts to separate the effects of low gravity on cells from the effects of low gravity on the cell growth medium will require meticulous experimental design, quantitative measures of cell alteration, and careful investigation of multiple experimental control groups. A thorough exploration of the factors affecting cell behavior in space will not only increase understanding of the effects of microgravity on cell and tissue formations but may also reveal unexpected information about the basic interactions between cells and their growth media.
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From page 22... ...
The Life Sciences Division covers a broad array of topics, including cellular and molecular biology, gravitational ecology, and organismal and comparative biology, that potentially relate to the cell science work under way in the Microgravity Research Division. Clearly, NASA and NASA-sponsored researchers would benefit from sharing and coordinating experiments on similar cell biology projects, such as the work on muscle growth and on osteoblasts.
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