After years of imagining and months of preparation, New York high school student Anna-Sophia Boguraev watched in amazement as her dream left the launch pad—her Genes in Space™ experiment was inside the Dragon capsule on the SpaceX-8 mission headed for the ISS. Boguraev’s experiment is a first step in determining whether modifications to DNA called epigenetic changes (changes that do not alter the sequence of bases that make up DNA) that are induced by spaceflight could be linked to immune system problems in astronauts living in space for an extended period of time.
“Since I was four years old, I watched rockets launch and all of the science being done in space, and I always wanted to be a part of it,” Boguraev said. “Then suddenly, I was part of it—I was standing there with a rocket launching three miles away going to the ISS, and it had my experiment on it!”
Boguraev is the inaugural winner of the Genes in Space™ contest, an annual competition in which students in grades 7 through 12 compete to send their DNA experiment to the ISS. The Genes in Space™ program is supported by a partnership between Boeing, CASIS, miniPCR, Math for America, and New England Biolabs.
“We want to make sure we’re doing everything possible to get the next generation of engineers and scientists engaged,” said Scott Copeland, Senior Manager for Research Integration, Specialty, and Systems Engineering at Boeing. “Competitions such as Genes in Space™ are designed to foster creativity, collaboration, and critical thinking among young innovators by incorporating active learning and real-world experience.”
Connecting Epigenetic Changes in Spaceflight to the Immune System
When brainstorming ideas for experiments she could do on the ISS, Boguraev immediately thought about the immune system of astronauts.
“In order to do something groundbreaking that would be useful for humans in space, my immediate thought was to focus on the immune system,” Boguraev said. “It bothered me that astronauts’ immune systems do not work as well during spaceflight, because it’s important for astronauts to be healthy.”
Boguraev had also read that spaceflight—both environmental factors (such as microgravity and radiation) and the stress induced by spaceflight—can cause epigenetic changes in the astronauts’ DNA.
Epigenetic changes are modifications made to DNA that do not involve changes to the DNA sequence. These modifications happen when chemical compounds attach to genes and affect gene expression. Boguraev knew that on Earth, some epigenetic changes can cause changes in the immune system.
This made her wonder—could the weakened immune system in astronauts be caused by epigenetic changes induced by spaceflight?
To begin to probe this question, Boguraev is examining a type of epigenetic modification called DNA methylation, which scientists have found can be affected by spaceflight.
DNA methylation happens when chemical compounds called methyl groups attach to cytosine bases in a strand of DNA. When regions of a gene are methylated, it prevents transcription and thus translation, so the gene is not expressed.
Photocopying Genes in Space
Boguraev’s long-term goal is to develop a method for use in space to evaluate epigenetic changes affecting the human immune system. Such a process could eventually lead to the ability to monitor changes in astronauts’ DNA during spaceflight and to develop countermeasures to boost their immune system when needed.
In her experiment, Boguraev used a miniPCR™ machine—a new instrument also sent to the ISS on SpaceX-8—to make billions of copies of specific genes in space for analysis back on Earth.
“It’s almost anticlimactic because it doesn’t look like much—it’s just a strip of eight tubes with a little clear liquid in it,” Boguraev said. “But I think that’s the coolest part about it—while in space, billions of copies of the genes are made, but you don’t see anything. The samples will come back, and it will still be eight tubes with clear liquid, but inside will be information we’ve never had before.”
Although PCR (polymerase chain reaction) is a common chemical reaction used to amplify DNA in labs on the ground, it had never been done in space. Standard PCR machines are large, expensive pieces of equipment that can be difficult to use, said Ezequiel Alvarez-Saavedra, co-founder of miniPCR™.
The miniPCR™ machine works the same way as a standard PCR machine, but it is much more compact—small enough to hold in the palm of your hand.
“We wanted to build something that could be used by anyone who wanted to do DNA analysis,” Alvarez-Saavedra said. “So what we’ve done is create a miniPCR™ machine that is very affordable, much more portable, and is easy to use.”
Detecting Epigenetic Marks
Boguraev used the miniPCR™ machine to detect DNA methylation in genes using a technique called “methylation-specific PCR.” For this technique, scientists start by treating a DNA sample with the chemical compound sodium bisulfite. This converts all un-methylated cytosine bases in the DNA into uracil while leaving the methylated cytosine bases unchanged. Uracil is one of the bases that make up RNA by replacing the thymine that is found in DNA.
Next, scientists use PCR to amplify genes in the bisulfite-treated DNA sample. Two separate PCR experiments are done simultaneously—one with primers that would amplify methylated DNA and one with primers that would amplify un-methylated DNA. In this way, scientists can determine whether the sample contained methylated and un-methylated regions of the DNA.
Boguraev’s validation experiment aimed to confirm that both standard PCR and methylation-specific PCR work the same way in space that they do on the ground. To do this, she used zebrafish DNA in different states of methylation.
To test methylation-specific PCR, the zebrafish DNA was bisulfite-treated on the ground and then separated into two samples—one to be sent to the ISS and one kept on the ground. Both the spaceflight and ground samples were run through a miniPCR™ machine using the same protocol.
Boguraev’s samples returned to Earth in May on the Dragon capsule, and analysis of the samples confirmed positive results. This successful proof-of concept experiment not only enables research aimed at improving the health of astronauts in space, it also opens the door for future ISS National Lab experiments that seek to use PCR to improve human health on Earth.
Although Boguraev’s samples are back on the ground, the miniPCR™ machine will stay on the ISS as part of the Boeing Science Enrichment and Engagement Kit for future ISS National Lab research and Genes in Space™ student projects.
“The Genes in Space™ program provides a unique opportunity for students to design an experiment for a laboratory unlike any on Earth,” Copeland said. This year, the Genes in Space™ contest received more than 300 applications submitted by more than 1,000 students (some students work in teams). The hope is that the program will continue to expand and reach more students each year.
The idea behind the Genes in Space™ program is to get students excited about science and to get them to start thinking like researchers,” said Alvarez-Saavedra. “What we’ve seen so far is that combining biology and space ignites the imagination of students—teachers have told us they have never seen their students so excited about science, and that’s exactly what our goal was.”
“The idea behind the Genes in Space™ program is to get students excited about science and to get them to start thinking like researchers,” said Alvarez-Saavedra. “What we’ve seen so far is that combining biology and space ignites the imagination of students—teachers have told us they have never seen their students so excited about science, and that’s exactly what our goal was.”