The Human Genome Project, launched in 1990, eventually produced a full sequence of human DNA, but many of the physical rules governing how that genome is organized inside cells remain unclear—including the influence of one force that’s present everywhere on Earth: gravity.
A new study in Science Advances tackles that question with an unusual approach: creating a zero-gravity, or microgravity, environment to study how a human cell’s genome behaves without gravity acting on it. The method serves two purposes at once—isolating gravity’s effect on the genome by removing it from the equation, and showing how the genome might function in the true zero-gravity conditions of outer space.
“On Earth, the role of gravity is intriguing—it is a constant mechanical stress on everything,” says NYU’s Alexandra Zidovska, who led the study. “We wanted to know what gravity’s role is in the genome’s organization and function here on Earth. To uncover it, you have to remove gravity as a force so we simulated zero gravity in our experiments.” The question matters beyond Earth too, she adds: “Beyond Earth, the question of lack of gravity is also compelling: How will the human genome be affected when in outer space? We think our findings can be useful in better understanding how space travel affects us.”
The human genome is packed with remarkable density—two meters of DNA folded into a cell nucleus roughly 10 micrometers across, about the width of a silk fiber. That structure is tightly linked to function, and disruptions to it are associated with diseases including cancer and developmental disorders, yet the physical principles behind the genome’s organization remain poorly understood. As Zidovska puts it, “We do not know if or how the presence of gravity affects this organization and if the absence of gravity would cause genomic aberrations.”
To investigate, the NYU team built a custom random positioning machine—similar in principle to devices used in astronaut training—that rotates dishes of live, bubble-free cells along two independent axes to simulate weightlessness. They also developed new rotational algorithms to minimize the fluid flows that rotation normally produces (but that don’t exist in true zero gravity), plus separate algorithms to study how those flows alone affect cells. Together, these advances reduced both flow effects and cell clumping that had obscured results in earlier studies of simulated microgravity.
After exposing cells to simulated microgravity, to strong flows, or to neither for 24 hours, the researchers used detailed imaging to track changes in cell and nuclear shape and volume, the nuclear envelope, the genome’s organization and movement, and the nucleolus. Cells exposed to flows became elongated, while cells in simulated microgravity kept their shape, though their nuclei grew larger—suggesting gravity normally helps keep the nucleus more compact. The nuclear envelope’s thickness and structure stayed unchanged in both conditions, and the genome held onto its normal organization and motion after the 24-hour exposure. Simulated microgravity did not cause DNA damage, but exposure to flows did, and the nucleolus became smoother under either condition. The researchers note that these subtle changes could compound over longer exposures and eventually affect cell physiology.
“Our data show that the genome, its organization, and dynamics are incredibly robust and seem unaffected by gravity, or lack thereof, after 24 hours,” Zidovska says. “In the same way, these results suggest that the physical organization of the human genome may undergo minimal changes in outer space during comparable times. However, such changes could occur during longer exposures and due to DNA damage occurring in space.”
A new study in Science Advances tackles that question with an unusual approach: creating a zero-gravity, or microgravity, environment to study how a human cell’s genome behaves without gravity acting on it. The method serves two purposes at once—isolating gravity’s effect on the genome by removing it from the equation, and showing how the genome might function in the true zero-gravity conditions of outer space.
“On Earth, the role of gravity is intriguing—it is a constant mechanical stress on everything,” says NYU’s Alexandra Zidovska, who led the study. “We wanted to know what gravity’s role is in the genome’s organization and function here on Earth. To uncover it, you have to remove gravity as a force so we simulated zero gravity in our experiments.” The question matters beyond Earth too, she adds: “Beyond Earth, the question of lack of gravity is also compelling: How will the human genome be affected when in outer space? We think our findings can be useful in better understanding how space travel affects us.”
The human genome is packed with remarkable density—two meters of DNA folded into a cell nucleus roughly 10 micrometers across, about the width of a silk fiber. That structure is tightly linked to function, and disruptions to it are associated with diseases including cancer and developmental disorders, yet the physical principles behind the genome’s organization remain poorly understood. As Zidovska puts it, “We do not know if or how the presence of gravity affects this organization and if the absence of gravity would cause genomic aberrations.”
To investigate, the NYU team built a custom random positioning machine—similar in principle to devices used in astronaut training—that rotates dishes of live, bubble-free cells along two independent axes to simulate weightlessness. They also developed new rotational algorithms to minimize the fluid flows that rotation normally produces (but that don’t exist in true zero gravity), plus separate algorithms to study how those flows alone affect cells. Together, these advances reduced both flow effects and cell clumping that had obscured results in earlier studies of simulated microgravity.
After exposing cells to simulated microgravity, to strong flows, or to neither for 24 hours, the researchers used detailed imaging to track changes in cell and nuclear shape and volume, the nuclear envelope, the genome’s organization and movement, and the nucleolus. Cells exposed to flows became elongated, while cells in simulated microgravity kept their shape, though their nuclei grew larger—suggesting gravity normally helps keep the nucleus more compact. The nuclear envelope’s thickness and structure stayed unchanged in both conditions, and the genome held onto its normal organization and motion after the 24-hour exposure. Simulated microgravity did not cause DNA damage, but exposure to flows did, and the nucleolus became smoother under either condition. The researchers note that these subtle changes could compound over longer exposures and eventually affect cell physiology.
“Our data show that the genome, its organization, and dynamics are incredibly robust and seem unaffected by gravity, or lack thereof, after 24 hours,” Zidovska says. “In the same way, these results suggest that the physical organization of the human genome may undergo minimal changes in outer space during comparable times. However, such changes could occur during longer exposures and due to DNA damage occurring in space.”