Today, Mason’s project has expanded into a global-scale project called MetaSUB. Researchers from across the world are using metagenomics to swab and sequence DNA from built environments to understand the “genetic cartography” of Earth’s major cities. At such a large scale, the MetaSUB project requires eager participants, efficient methods, and reliable technologies. Mason and his colleagues coordinate a Global Sampling Day, using citizen scientists that participate around the globe. On the same day, at the same time, individuals are instructed to use the same protocol. They swab everything around the city: turnstiles, kiosks, benches, and more. Each swab is barcoded and scanned into a customized mobile app designed for the project.
Once the samples have been collected, the teams need to extract DNA. When working with large data sets, the quality of the samples, the extraction methods and instrument sensitivity can all influence data analysis. Mason's team uses Maxwell® Instruments for most of the DNA extraction and then perform next-generation sequencing on the Illumina platform, or long-read platforms like Oxford Nanopore.
“Automation is key, because you want to reduce any batch effects or problematic areas of technician error,” he says. Additionally, when extracting DNA from samples of unknown material from unique sources, low input is a concern when a high yield is desired. “[Maxwell] actually solved all those problems for us. It was great.” He estimates that they have collectively extracted DNA from about 10,000 samples and have sequenced about half of them. The plan is to continue sampling through 2020, and get about 30,000 samples total.
The project has three major goals: 1) Discover what is around us; 2) Track antimicrobial resistant markers; and 3) Scan for new biosynthetic gene clusters. “In a world where you don’t know what to look for, the best thing to do is explore,” says Mason. As it happens in science, the unknown often leads to more unknowns, driving the scientific method of inquiry. In the inaugural New York City study, Mason and his team discovered many new fragments of DNA that had never been seen before. In any given sample, almost 50% of the DNA did not match any previously known organism, human or otherwise (3). Additionally, collected data provides a dynamic overview of antimicrobial resistant markers and biosynthetic gene clusters. Different “hotspots” appear in different cities. Mason believes that this data will aid the development of new antibiotics or other molecular drug compounds that reduce the risks of disease transmission or bioterrorism. He doesn’t interpret these findings through fear, but through hope that they will inform better decisions about public health and preserving humanity.
Discovery efforts don’t stop in our home cities—or our home planet. Mason’s next mission is bringing his curiosity into outer space and beyond. “I went to space camp as a kid, so I’ve always been interested in space,” says Mason. Given the chance to combine his love of space with his love of genetics, he was ready to explore more of the unknown.
The International Space Station (ISS) is a collaborative project that launched into orbit in 1998. It serves as a research environment for a variety of science fields, collecting data on the effects of zero gravity and exposure to space. It has been continuously occupied by a crew of up to six researchers since November 2000, with visits from over 200 people from 18 different countries. While most missions last between 4–6 months, astronauts Scott and Mark Kelly, identical twins, became the subjects of the NASA Twins Study, a year-long mission to study the effects of space on the human body. Scott Kelly commanded the ISS as the “test subject” in orbit, while Mark Kelly remained on earth as the “control subject”.
Mason joined the project to specifically understand how human genetics might be influenced by space travel. “We wanted to get DNA, RNA and microbiome samples. We looked at everything we could, all the -omics, and profiled them,” says Mason. “It’s helped us think about getting to Mars.” As the first mission to use genomics to investigate changes in the human body, the Twins Study set the precedent for long-term space exploration. Scott Kelly spent nearly a year in space in 2015, and now nearly three years later, the results of the study have been published (4). In almost all areas of the study, collaborators reported changes in Scott Kelly’s body that were specific to spaceflight when compared to data from Mark Kelly on Earth.
Mason and his team discovered that the human body is extremely resilient, but also prone to damage. “The body is extraordinarily responsive and has a lot of plasticity in terms of responding to the dangers and molecular slings and arrows of space flight,” says Mason. Six months after being back on Earth, most of Kelly’s physiology—such as cardiovascular changes, body mass or the composition of the microbiome—returned to normal. However, the less visible changes, those made at the cellular and genetic level, might be more long-term. Mason says that one major finding was the stress that space flight caused on Scott Kelly’s immune system. His immune cells showed the release of many molecules that signal inflammation. “It’s almost like the body is on high alert,” Mason says, “But it’s still functional.”
Kelly received an influenza vaccination while in orbit, and data showed that the immunization still worked and there were no significant differences in his influenza-specific T cell responses compared to those seen on Earth. Additionally, gene expression levels in almost 9% of Scott Kelly’s genes did not return to baseline levels after six months post-flight. This handful of genes include those involved with immune function and DNA repair, as well as blood clotting and bone growth. “There’s no flashing red lights, more like yellow lights—things we want to keep an eye on and measure for future missions.”
Unrelated to the Twins Study, Mason also conducted a study to explore the microbiome of the ISS itself, not unlike the NYC subway project. The astronauts took swab samples of various locations around the ISS, including crew quarters, the dining table, the foot platform of the exercise equipment, and the waste and hygiene compartment (5). Nearly 60 strains of known bacterial organisms were identified on the space station. 92% of these were resistant to penicillin, though other antibiotics were more effective.