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. Today's ground-based protein crystallization projects are increasingly sophisticated, and yet the diffraction characteristics of crystals of many important targets are still suboptimal. Improvements in diffraction that move a system from the margins of structure determination to well beyond that boundary will have a significant impact on the ability of the resulting structure to provide important insights into biological mechanisms. All research on protein crystallization in space has, up to now, been done under suboptimal conditions (short-duration experiments, insufficient vibration control, etc.), so the improved conditions for research provided by the ISS have the potential to produce much better results.

Finding: While enormous strides have been made in protein crystallization in the last decade, it is still the case that there are very important classes of compelling biological problems where the difficulty of obtaining crystals that diffract to high resolution remains the chief barrier to structural analysis of the crystals. It is here that the NASA program must look to maximize its impact.

In order to engage the research community, NASA must focus its support on programs that are developing technologically innovative equipment and engaging in the structure determination of crystals with important biological implications. While past NASA-supported research on the crystallization process has not been without value, NASA's priority should now be to resolve the community's questions about the usefulness of protein crystal growth in the microgravity environment for tackling important biological questions. Until the uncertainty about the value of space-based crystallization is resolved, a program of this fiscal magnitude is bound to engender resentment in the scientific community.

Although many pharmaceutical and biotechnology companies have participated in microgravity crystallization research, not one has yet committed substantial financial resources to the program. This is likely to remain the case until the benefits of microgravity can be convincingly documented by basic researchers and until facilities in space can handle greatly increased numbers of samples in a much more user friendly manner.

Cell Science

NASA's cell science program focuses on studying the influence of low gravity on fundamental cell biology as it relates to tissue formation, and on providing insight into the effects of microgravity on cell, tissue, and organ system function, especially as it might affect participants in space exploration.

Finding: It is appropriate for NASA to support a cell science program aimed at exploring the fundamental effects of the microgravity environment on biological systems at the cellular level. Results from such basic research experiments could have a significant impact on the fields of cell science and tissue engineering. However, the specific important questions within cell biology that can best be tackled on the ISS do not seem to have been defined yet. Narrowing the broad sweep of the current program may focus instrument development efforts and accelerate progress toward complete understanding of the effects of microgravity on specific biological phenomena.

A key to determining the success of cell science experiments in space will be designing appropriate controls for experiments. In space, cell cultures experience a low gravitational environment that reduces convection, buoyancy-driven flows, and sedimentation, and it is difficult to separate the various factors causing differences between space-and Earth-grown samples. In addition, the tremendous progress that has been made in three-dimensional tissue development on Earth, under unit gravity, provides a wide range of options for ground-based experiments that may produce results similar to those achieved in microgravity. To evaluate the relative merits of various experimental control groups, and also to enable the detailed evaluation of samples returned from space, it is important that quantitative measures of cell and tissue structure and function be developed and studied.

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