For more than two decades, the International Space Station has provided a platform for growing and studying protein crystals. In the early days of microgravity research, scientists discovered that they protein crystals grown in space were more uniform and larger than those grown in Earth’s gravity. Since then, drug companies and academic researchers have conducted hundreds of protein crystal growth (PCG) experiments on the space station – by far the largest single category of experiments conducted on the orbiting lab.
Proteins are involved in every aspect of our
lives, including as essential components of our immune system and as parts of
viruses that can make us sick. When we take a medication, it binds to a
specific protein in the body. This process changes the protein’s function – and
if it works properly, that can make us well.
ESA (European Space Agency) astronaut Thomas Pesquet and cosmonaut Fyodor Yurchikhin pose with canister bags from the Protein Crystallization Research Facility (PCRF) during Kristallizator operations. Credits: NASA
In many diseases,
the proteins that can trigger the disease state fit into very specific
locations, like a biological keyhole. The protein of a potential drug for
treating that disease must be designed to fit that keyhole. A good key and
keyhole fit results in a more effective medicine with fewer side effects, but
to achieve that fit, scientists need detailed knowledge of the structure of
both proteins. One of the best ways to analyze a protein structure is to grow
it in crystalline form.
Since 2005, the Kristallizator program from the State Space
Corporation Roscosmos has created single protein crystals especially suited for
analysis using X-ray diffraction. One outcome of these studies was
identifying the structure of a target for anti-tuberculosis drugs, which could
help scientists develop a treatment.
Protein crystals form in microgravity in the space station’s Kibo Module. Credits: JAXA
JAXA (Japan
Aerospace Exploration Agency) has been active in protein crystal growth research in microgravity, accounting
for about two-thirds of all PCG experiments on the station. A series of studies, JAXA PCG, has provided precise structures of many protein types and has led to the discovery of
potential drugs.
One of these studies examined the crystal structure of a
protein associated with Duchenne Muscular Dystrophy (DMD), a currently
incurable genetic disorder. The work provided hints for compounds that could
inhibit the disease, leading to several promising compounds, including one
called TAS-205. The research team estimates the drug may slow the
progression of DMD by half, increasing the lifespan of many patients. A clinical trial in human patients was completed in
2017. Co-investigator Mitsugu Yamada of JAXA says a larger Phase 3 trial to
examine the effectiveness of TAS-205 in situations similar to actual clinical
use began in December 2020 and will continue until 2027.
JAXA Moderate Temperature PCG continued this work, producing high quality
crystals to advance basic biochemical knowledge and support drug discovery.
In addition to creating completely new
treatments, PCG research on station can lead to drug formulations that are
easier to store and last longer – such as those stable at room temperature that
eliminate the need for refrigeration. This modification lowers the cost and
simplifies distribution of drugs.
JAXA astronaut Koichi Wakata prepares Moderate Temperature PCG samples to ride the SpaceX Dragon cargo craft back to Earth for additional analysis. Credits: NASA
PCG-5, work sponsored by the ISS National Lab,
focused on how drugs known as monoclonal antibodies are given to patients.
Monoclonal antibodies do not dissolve easily in liquid and typically are
delivered intravenously, requiring a patient to spend hours in a clinic
setting. High-quality crystalline suspensions produced by PCG-5 could enable delivery by injection,
making treatment more convenient for patients and caregivers and significantly
reducing cost.
Merck Research Laboratories, developer of
a series of PCG experiments, produced simple hardware and processes that
scientists from other disciplines can use to conduct microgravity research.
JAXA has worked to increase interest in PCG research in microgravity as well,
developing a technology for membrane protein
crystallization, for example. Other studies have advanced the field of protein
crystallization by producing new processes for growing
high-quality crystals aboard the space station.
By providing a platform for PCG research,
the space station plays a key role in bringing people on Earth new and better
treatments for diseases.
For daily updates, follow @ISS_Research, Space Station Research and Technology News or our Facebook. Follow the ISS National Lab for
information on its sponsored investigations. For opportunities to see the space
station pass over your town, check out Spot the Station.
Resources for Additional Learning
Related Experiments:
Crystallizing Biological Macromolecules
and Obtaining Biocrystalline Films in Microgravity Conditions (Kristallizator)
JAXA PCG
JAXA Moderate Temperature PCG
PCG-5
Crystallization of LRRK2 Under Microgravity Conditions-2 (CASIS PCG 16)
Structural and Crystallization Kinetics Analysis of Monoclonal Antibodies (Monoclonal Antibodies PCG)
Screening and Batch Manufacture of Complex Biotherapeutics in Microgravity (Monoclonal Antibodies PCG-2)
Monoclonal Antibody Stability in Microgravity-Formulation Study (CASIS PCG 19)
Learn More:
Crystallizing Proteins in Space
Helping to Identify Potential Treatments for Diseases
20 Breakthroughs from 20 Years of
Science aboard the International Space Station
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