To advance scientific discovery in new ways, scientists are taking their experiments and labs to an environment unlike any other: the International Space Station (ISS). But it is not just scientists from companies and research institutes conducting space-based studies. Students are also doing transformative research on the ISS and making significant scientific contributions, even publishing their results in peer-reviewed journals.
Through Genes in Space™, an annual student research competition founded by Boeing and miniPCR bio and supported by the ISS National Laboratory and New England Biolabs, students in grades 7 through 12 can propose pioneering DNA experiments that utilize the unique environment of the ISS. The winning proposals are developed into flight projects carried out on the space station. Investigations from high school students participating in the Genes in Space program have resulted in six journal publications, including three in the last year.
One recent study, published in PLOS One, edited DNA in space for the first time as part of a project to mitigate the effects of radiation exposure during spaceflight. Another investigation, published in Gravitational and Space Research, developed a technique to monitor and evaluate the immune system of astronauts in space. And a third experiment, also published in Gravitational and Space Research, proposed a way to monitor DNA changes in astronauts as they are happening. Results from these student-led investigations have important applications in space and back on the ground.
“Currently, there are just so many unknowns about how life responds to the conditions of space, and we’ll need to solve those mysteries before we can establish a long-term presence in low Earth orbit,” said Genes in Space program lead Katy Martin. “The idea behind the competition is to open the door and invite students to lead the investigations that get us those answers.”
These three recent Genes in Space experiments used a process called polymerase chain reaction (PCR) that makes millions of copies of targeted pieces of DNA, making them easier to detect and analyze. In labs on the ground, the average PCR machine, or thermocycler, is the size of a microwave. However, on the ISS, crew members perform PCR using a compact and energy-efficient instrument developed by miniPCR bio that is small enough to hold in the palm of your hand.
“Anna-Sophia’s experiment in 2016 marked the first time a molecular biology experiment was performed in space, opening up a new era of science,” said Sarah Wallace, a microbiologist at NASA’s Johnson Space Center. “If we can do these types of molecular biology processes using miniaturized equipment in space, then we can do them in hospitals, doctor’s offices, and other resource-limited environments.”
CRISPR in Space
Four Minnesota high school students can tout something no other student or scientist can: Their experiment was the first to edit DNA in space. The investigation used a genome editing tool called CRISPR-Cas9 to create breaks in specific areas of DNA. On Earth, this technology has been used since 2012 to edit the genes of plants, animals, and human cells with great precision. It is so important to research and so widely used that two researchers were awarded the 2020 Nobel Prize in Chemistry for contributing to its discovery. Validation of CRISPR technology onboard the ISS opened the door to a whole new realm of molecular biology research.
For the 2018 Genes in Space competition, high school students Aarthi Vijayakumar, Michelle Sung, Rebecca Li, and David Li designed their investigation to help mitigate the adverse effects of radiation exposure during spaceflight. Increased exposure to radiation in space has been shown to damage DNA, leading to serious health risks, including cancer.
Specific proteins in bacteria called Cas proteins—in this case, Cas9—act like molecular scissors, cutting the DNA. To control where the DNA is cut, scientists add a specific RNA strand to the Cas9 protein and insert it into a cell. Using RNA as its guide, the protein travels along the DNA strands until it finds the corresponding sequence and makes a cut.
On Earth, the human body can repair DNA damaged by breaks in the DNA strand in two ways: by adding and deleting DNA bases or by re-joining the two pieces without altering them. However, conditions in space could affect this process, so the student team proposed their experiment to see whether DNA could be successfully broken and then repaired during spaceflight.
“We looked at existing research, and people had tried to study how DNA repair is affected by microgravity by looking at the expression of different genes that are relevant to DNA repair,” Vijayakumar said, “but no one had actually edited DNA in space before.”
Conducted with the help of NASA astronaut Christina Koch, the student-led experiment successfully used CRISPR to generate breaks in the DNA of a common yeast and then direct the method of repair. The repaired DNA was then sequenced to determine whether its original order was restored—a process never before attempted in microgravity.
While the project was a proof of concept, the results lay the foundation for further research on DNA repair in space. Wallace said that more work is needed to fully understand the repair processes but having a miniaturized molecular biology toolkit is valuable both for space-based research and for use in hospitals and labs on the ground.
“Instead of sending samples to labs, we can take the labs to the samples,” Wallace said. “We are looking at how to put these methods into other settings such as hospital rooms and resource-limited environments.”
The goal is improving patient care, she added. “In today’s world, human diagnostics are crucial—whether it’s COVID testing or cancer screening—and it’s all molecular, so the types of experiments these students are proposing are transformative.”
TREC-ing Through Space
In 2017, Liza Reizis was a high school student in New York researching a homework assignment. She was fascinated by immunology but never imagined she would conduct a science experiment onboard the ISS to test a technique for monitoring the immune systems of astronauts in space.
“During my research, I discovered that when astronauts come back from space, their immune systems are very depressed,” Reizis said. “I wanted to understand what part of their immune system was affected.”
This curiosity led her to do more research and design an experiment for the Genes in Space competition. Reizis learned about T-cell Receptor Excision Circles, or TRECs, which are tiny segments of DNA the body produces as a byproduct of immune cell development. These bits of DNA may seem insignificant, but she soon learned that by studying them, you can determine how many new T-cells the body is making, which directly correlates to how well a person’s immune system is functioning.
For her Genes in Space investigation, Reizis focused on T-cells because they’re the most prominent type of immune cell, leading the body’s fight against disease and regulating the response of other immune cells. Her proposal involved using an assay to measure the amount of TRECs produced by T-cells.
Reizis postulated that this type of immune test, typically performed on infants on Earth to test for immune system disorders, could be performed on blood samples from ISS crew members. This would allow astronauts to evaluate how well their immune systems function in space. However, the process first had to be validated onboard the space station to ensure it worked as well in microgravity as it does on Earth.
Reizis designed her experiment to utilize miniPCR technology to measure the number of TRECs in biological samples sent to the space station. She sent blood samples from mice of different ages and genders to see how effective the miniPCR device was at detecting TRECs.
PCR (polymerase chain reaction) is a common chemical reaction used to amplify DNA. First developed in 1983, the process essentially makes copies of specific sections of DNA targeted by small pieces of complementary DNA called primers. A cycle involving three steps is repeated about 30 times to produce billions of copies of DNA sections for analysis.
The proof-of-concept experiment was successful and paved the way for researchers to develop a safe and reliable way to monitor immune system function in space. Reizis’ project also has implications for patients here on Earth, especially those affected by HIV and AIDS. This type of test could help patients more effectively measure the production of T-cells, which are directly affected by these diseases. A test using miniaturized equipment could lead to new ways of monitoring immune system function at home, improving patient care and quality of life, said Wallace.
Scanning DNA for Microsatellites
Reizis was not the sole winner of the 2017 Genes in Space competition. Washington state high school student Sophia Chen joined her in the competition’s first-ever tie. Chen was interested in developing new ways to protect astronauts from the harmful effects of cosmic rays, which can damage DNA and lead to mutations that can potentially cause serious health problems, such as cancer.
“I was interested in focusing on something cancer-related—and, in particular, why astronauts have an increased risk of cancer—when I came up with the idea for this project,” Chen said. “That’s when I came across DNA markers known as microsatellites.”
Exposure to damaging radiation and other hazards of the space environment can affect the integrity of the genome, including how the human body repairs itself. This is where DNA sequences known as microsatellites—or highly repeatable segments of noncoding DNA composed of repeating base pairs—come into play. These bits of DNA are useful as markers of genomic stability and can indicate an individual’s predisposition to cancer. Changes in the length of a person’s microsatellites over time suggest that they have experienced DNA damage and may be at risk of developing cancer.
Chen proposed a way to monitor changes in DNA by using miniPCR technology to amplify DNA regions with microsatellites in them. The ability to measure microsatellite sequences in space could be used to monitor astronauts’ health by keeping tabs on the integrity of their DNA throughout a mission. That way, medical staff can assess whether certain individuals have an increased risk for cancer during spaceflight.
“We used both normal cell lines and cell lines known to have unstable microsatellites—which means the repeating segments are either longer or shorter than normal—in order to validate our method to see if we’re able to accurately detect the microsatellites,” Chen said. “With the help of miniPCR, we were able to measure changes in microsatellites in our samples.”
Terrestrially, microsatellites are used for various forms of DNA profiling or genetic fingerprinting, which is useful in forensics and testing tissues for transplant patients. These segments of DNA are also used in cancer diagnosis. Results from Chen’s experiment could help lead to new portable diagnostic tools that work in tandem with the miniPCR machine to help people monitor changes in their health. This would be especially beneficial to those in remote areas and developing countries who may not have access to sophisticated laboratory equipment.
Igniting a Spark in Students
“The goal of Genes in Space is to inspire the next generation of engineers and scientists,” said Scott Copeland, director of ISS research integration at Boeing and co-founder of the Genes in Space program. “This is the perfect platform to do so, as the program is designed to spark imagination and foster critical thinking as well as collaboration among students by incorporating active learning and real-world experience.”
Genes in Space encourages students to start thinking like researchers, enabling them to tackle real-world issues. By providing opportunities to conduct investigations leveraging the ISS National Lab, the program allows students to make real contributions to the scientific community.
Before 2016 and the debut of the Genes in Space program, the ISS lacked a molecular biology platform, said Wallace. “These student-designed experiments are truly advancing the science we’re able to perform on the space station and enabling areas of research never done in space,” she said. “It really blows me away at how elegant and sophisticated the students’ studies have been.”