Crystal Clear: Protein Synthesis, Space, and Microgravity 

Protein research in microgravity holds tremendous promise. Still in its infancy, it has already helped improve the delivery efficiency of a life-saving therapeutic while making it less expensive (Braddock, 2020; Reichert, 2019). 

X-ray crystallography for the structural elucidation of large molecules has improved drastically thanks to microgravity. At one point a single protein structure could take years of work to unravel. With microgravity, particularly high throughput solutions provided by companies like Litegrav, this process can be greatly expedited (McPherson, 2015).

Along with this desperately needed efficiency comes an even more significant benefit. Just as plants grow in a peculiar manner in space, so too do proteins crystallize in unique and unexpected ways.

The Benefits of Microgravity

Employing microgravity for crystallization experiments confers advantages for the formation of higher quality protein crystals. 

Researchers have database access collecting information from studies which make it seamless to compare different types of crystals and their applications. A study conducted by Jackson et. al. found crystals cultivated in microgravity displayed improvements in size, uniformity, structure, and overall performance (Jackson, 2024).

This stands in stark contrast to synthesis upon our weighty world, where small cracks can be a hindrance to the actuation of the crystal’s desired properties. Microgravity environments bestow less convection, giving rise to purer crystals. This is the reason NASA cultivates crystals on the International Space Station (ISS), where a myriad of high quality crystals can be made (NASA, n.d.). 

Protein crystallography is far more effective in microgravity conditions, where they are brought into the path of an X-ray beam. The diffractions of this are then recorded as images, which result in a 3D structural image of the protein. Obtaining a 3D version of a protein confers knowledge on how a protein might function, or bind to drugs (Berman, 2024).

Microgravity also provides novel formation conditions that do not occur on earth, alongside superior quality to ensure their structures can be determined (Berman, 2024).

Applications in Drug Development

Microgravity has the tendency to produce higher-quality crystals. Well ordered proteins translate to strengthened diffracted waves and confer clarity to the structure, with well-ordered sharp spots on the screen. Contrarily, poor crystal yields cause obfuscation and diffuse spotting, and sometimes cause undetectable spots (JAEA, n.d.).

This becomes a momentous challenge when determining the structures of disease-causing proteins. Substandard crystals do not give accurate data. It is not reasonable to design medications for the treatment of disease nor to evaluate potential side effects with such crystallized proteins ((JAEA, n.d.). Safety and efficacy is paramount.

As they are larger and better structured than what can be produced on earth, The International Space Station (ISS) is conducting many experiments for pharmaceutical companies like Eli Lilly. This collaboration is advancing structure-based drug design. (ISS, 2023)

Academic researchers and pharmaceutical companies have conducted over 500 protein crystal growth experiments in just three years. These experiments are the largest experimental category on the station (NASA, n.d.).

Superior crystals facilitate drug candidate identification—which results in an improved likelihood of finding useful therapeutics.The enhanced efficiency of this process in microgravity saves money. Microgravity crystals may make more consumer-friendly formulations possible; they are finer, leading to smaller volume subcutaneous injections (Axiom Space, n.d.).

This research has been conducted for more than 20 years and has led to precise structures for many protein types and is leading to drug discoveries for a variety of ailments, from gum disease to muscular dystrophy. (NASA, n.d.).

More lies ahead: studies have shown microgravity has the potential to enormously benefit drug discovery and development in areas ranging from including cardiovascular disease, multiple sclerosis, cystic fibrosis, osteoporosis, and various cancers. (Axiom Space, n.d.)

Current Research Initiatives

Research on the space station has garnered knowledge that may address novel treatments for diseases like Duchenne Muscular Dystrophy (DMD), a currently incurable genetic disorder. By its associated dysfunctional protein, scientists designed a promising drug called TAS-205, which may inhibit disease progression (ISS Program Science Office, 2022).

Another study focused on improving how Merck’s Keytruda, a cancer medication, is given to patients. The goal was to make it quickly injectable instead of requiring long IV infusions. This was achieved with microgravity, which drastically cut costs to the patient (Reichert, 2019).

A research team has also discovered that a speedier and novel process can result in  growing premium crystals of the antipsychotic drug Olanzapine. This process may deepen our understanding of the underlying chemical structure and processes of Olanzapine, culminating in better psychiatric medications  (Warzecha, 2020).‍

Microgravity Simulation Opportunities and Future Directions

Technologies that enable microgravity research on Earth, like those offered by Litegrav—including in-silico discovery algorithms, in-lab validation with modular simulator units, and small-scale wet lab production—are invaluable tools for conducting parallel research in space-like conditions. 

While these platforms may not replace the need for space missions, they offer a complementary approach by providing insights that can either resemble or diverge from what is observed in space. In many cases, they can help optimize research processes and outcomes here on earth.

Protein crystallization in microgravity is a momentous new chapter in the history of medicine. Companies like Litegrav are making it, and its benefits, accessible to all. 

References and Works Cited

Axiom Space. (n.d.). Protein crystallization. Axiom Space. https://www.axiomspace.com/research/protein-crystallization

Berman, J. (2024, April 4). ASU researcher successfully launches protein crystals into space. Arizona State University. https://news.asu.edu/20240404-science-and-technology-asu-researcher-successfully-launches-protein-crystals-space

Braddock, Martin. "From target identification to drug development in space: using the microgravity assist." Current Drug Discovery Technologies 17.1 (2020): 45-56.

ISS National Laboratory. (2023, February 21). Crystallizing proteins in space for drug development. ISS National Lab. https://issnationallab.org/iss360/crystallizing-proteins-in-space-for-drug-development/

ISS Program Science Office. (2022, May 31). Station science top news: May 26, 2022. NASA Roundup Reads. https://roundupreads.jsc.nasa.gov/roundup/1937

Jackson, K.; Brewer, F.; Wilkinson, A.; Williams, A.; Whiteside, B.; Wright, H.; Harper, L.; Wilson, A.M. Microgravity Crystal Formation. Crystals 2024, 14, 12. https://doi.org/10.3390/cryst14010012

Japan Aerospace Exploration Agency. (n.d.). Structural analysis of proteins. JAXA. https://humans-in-space.jaxa.jp/protein/en/public/about/structural_analysis.html

McPherson A, DeLucas LJ. Microgravity protein crystallization. NPJ Microgravity. 2015 Sep 3;1:15010. doi: 10.1038/npjmgrav.2015.10. PMID: 28725714; PMCID: PMC5515504.

NASA. (n.d.). Crystallization in microgravity. NASA Science. Retrieved October 6, 2024, from https://science.nasa.gov/biological-physical/stories/crystallization/

NASA. (n.d.). Crystallizing proteins in space: Helping to identify potential treatments for diseases. NASA. https://www.nasa.gov/missions/station/iss-research/crystallizing-proteins-in-space-helping-to-identify-potential-treatments-for-diseases/

Reichert, P., Prosise, W., Fischmann, T.O. et al. Pembrolizumab microgravity crystallization experimentation. npj Microgravity 5, 28 (2019). https://doi.org/10.1038/s41526-019-0090-3

Warzecha, M., Verma, L., Johnston, B.F. et al. Olanzapine crystal symmetry originates in preformed centrosymmetric solute dimers. Nat. Chem. 12, 914–920 (2020). https://doi.org/10.1038/s41557-020-0542-0

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