To find out important factors controlling crystal growth rate and perfection of protein crystals in microgravity, a microgravity experiment using a Foton-M3 has been conducted in September 2007. Using seed crystals at constant supersaturation, the growth rate was successfully measured ex-situ for the first time to be 0.7-1.5 times larger than the rate under gravity. The result was very surprising because large reduction of growth rate under reduced gravity has been expected. This experiment will be continued as a “NanoStep” project, which will be started on 21st, July 2012.

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The formation of a protein depletion zone (PDZ) and an impurity depletion zone (IDZ) around a growing crystal due to the suppression of a convection flow were thought to be the major effects of microgravity on higher quality protein crystal growth. We studied those effects numerically using a simplified model, and found out that the combination of the diffusion coefficient of the protein molecule (D) and the kinetic coefficient for the protein molecule (β) could be an index of the extent of these depletion zones. According to this analysis, we recommended to use high-viscous crystallization reagent to decrease D on purpose and further-purified protein sample to increase β for microgravity experiment. As a result, for some protein samples, this approach may have increased the microgravity effects and grew higher quality crystals. There are still some more details to be elucidated, but when our technology is more established and can be applied to more variety of protein samples, the crystallization in microgravity will be more useful method and will contribute to the X-ray structural analysis more practically. In this article, we explain current status of JAXA PCG, and introduce the rational approach to high-quality protein crystal growth experiment in microgravity based on numerical analyses.

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Sample quality is one of the important points for getting high quality protein crystals. Especially, in the case of the crystallization under microgravity, not only the purity of the sample, but also “uniformity of the sample” is quite important factor. By using highly purified protein sample, crystal quality could be improved by the protein crystallization experiments onboard “Kibo” conducted by Japan Aerospace Exploration Agency (JAXA). According to results of crystallization by using samples without highly purification under microgravity as scientific control, crystal quality could not be improved effectively. Structure analysis by using high quality crystals obtained by space experiments reveal more detailed three-dimensional information of protein structures, water networks, interactions between enzyme and substrates/inhibitors.

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Duchenne muscular dystrophy (DMD) is a severe X-linked muscle disease characterized by progressive skeletal muscle atrophy and weakness. DMD is caused by mutations in the dystrophin gene, which encodes the cytoskeletal protein dystrophin. We have found that hematopoietic prostaglandin (PG) D synthase (H-PGDS) was induced in grouped necrotic muscle fibers in DMD patients. Oral administration of HPGDS inhibitor HQL-79 prevented the expansion of muscular necrosis in genetically dystrophin-deficient mdx mice and recovered the muscle strength. We obtained high quality crystals of H-PGDS-inhibitor complexes by crystallization under microgravity conditions within the International Space Station, determined X-ray crystallographic structures at a high resolution, and developed novel potent inhibitors highly selective to H-PGDS. The treatment of DMD dogs with a novel H-PGDS inhibitor prevented skeletal muscle atrophy and weakness without any side effects. These results indicate that H-PGDS inhibitors are useful for drug therapy of DMD patients.

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The recent development of the field of molecular biology is amazing, and many biological functions are being elucidated. Most of the biological phenomena are induced by the reactions between biological macromolecules, so it is very important to determine the structure of these molecules precisely at atomic resolution. Protein X-ray crystallography is one of the most powerful techniques to determine the protein structure at atomic resolution. As of May 2012, more than 71000 structures of the biological macromolecules are determined by X-ray crystallography, but the resolution of most of the structures is not enough. It is impossible to reveal high-resolution structures without high quality crystals. Crystallization in microgravity environment is one of the most powerful methods to improve quality of the crystals. We are working on the improvement of protein crystals based on the crystallization under microgravity environment and development of methodolgy of high-resolution X-ray crystallography. The results of our project on high-quality crystallization of the small protein to large viruses and technical developments on data processing are presented in this review.

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One of the objectives of the International Space Station(ISS) is to introduce impressions that human beings have never experienced and expand the wisdom of human beings by exploring the space environment.

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JAXA has conducted the educational activity in KIBO since JAXA astronauts started the long-term stay onboard. JAXA designed educational experiments using the unique environment which is very different from the ground and educational interactive event as educational activities. These activities help to enlighten the general public about microgravity utilization and human space flight via crewmember performances of on-orbit demonstrations exhibiting that microgravity is useful not only for scientists and engineers, but also for teachers. Through the continued educational activities, we will inspire the next generation of scientists, engineers, writers, artists, politicians and explorers.

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JAXA has started the KIBO Commercial Utilization in 2007. The purposes of the commercial utilization are to provide diversifying scope of KIBO utilization and to promote “KIBO” utilization. The user has to pay necessary fee for the commercial utilization. Then consequently, the user can exclusively use the outcome of the mission. This paper provides the outline of the KIBO Commercial Utilization.

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