It’s been known for decades that astronauts’ immune systems become suppressed in space, leaving them susceptible to disease, but the exact mechanisms of the immune dysfunction have remained a mystery — now a Cornell undergraduate student has found a potential solution.
Rocky An ’23, a double major in biological and mechanical engineering in the College of Engineering, published his theory, “MRTF may be the missing link in a multiscale mechanobiology approach to macrophage dysfunction in space,” Sept. 12 in Frontiers in Cellular and Developmental Biology.
The literature of the past 20 years on the behavior of macrophages – key cells in the body’s immune response – has been reviewed in space and recent research on how macrophages respond to natural gravitational forces, identifying a transcription factor that could be missing a piece of the puzzle.
“I kept asking questions about how to present the data,” Ann said. “There are two really important papers, in particular, one is a review of how macrophages suppress in microgravity, and the other is on the mechanical biology of macrophages. I was able to connect those two papers, and that’s when the idea came to me. He was really excited, because it was kind of a Eureka moment for me. Mine “.
In space, lack of gravity alters the shape of the immune cell, and scientists suspect that changes in the cytoskeleton, the cell’s filamentous infrastructure, were involved in the immune dysfunction. Recent studies in normal gravity have shown that disruption of the macrophage cytoskeleton reduces the transport of a specific protein, an important transcription factor for the immune response, into the nucleus.
By comparing cell studies in microgravity and analyzing associated study patterns and time scales—whether macrophages were actually studied in space, on an equivalent plane, or in microgravity simulations in vitro—he was able to signal this protein, a transcription factor associated with Myocardin (MRTF), as a possible cause of impaired immune system.
“I think it’s a very compelling argument that the MRTF is a big part of the problem,” Ann said. “I hope it will inspire future studies that really focus on this protein and its cytoskeleton, and maybe it could be the first step toward immunotherapy for spaceflight.”
The paper suggests that MRTF could be involved in stressing astronauts’ cardiovascular health as well. A also points to other factors that may play a role in immune dysfunction and notes that more research is needed to understand how MRTF interacts with macrophage nuclei in microgravity.
While An worked independently on the publication, he credits his Cornell professors (including Mingming Wu, professor, and Minglin Ma, associate professor, both biological and environmental engineering in the College of Agriculture and Life Sciences; Brian J. Kirby, Meinig family professor). engineering; and Donna Cassidy Hanley, senior research associate in the College of Veterinary Medicine, among many other educators) to model an interdisciplinary approach and encourage inquiry.
Even before enrolling at Cornell University, Anne had been in contact with Theodore Clark, professor of microbiology and immunology at the College of Veterinary Medicine, where Anne had been involved in research since his freshman year. He also credits his experience on the Cornell iGEM (Genetically Engineered Machines) project team, with advice from Jan Lammerding, a professor at the Meinig School of Biomedical Engineering, for helping him develop as a scientist.
“The biggest help,” he said, “was from the professors and the way they taught my classes.” “And then with the research in the lab and my project team, there were plenty of opportunities to learn independently and ask our own questions.”
I also gained valuable summer internship experience. In 2021, he was selected as a Research Associate in NASA’s Space Life Science Training Program, where he studied the effect of microgravity on cells and co-authored his first paper, Refining the Modeling Framework for Studying Cells in Microgravity.
Ann spent the summer of 2022 as an Amgen researcher at Harvard University’s Wyss Institute, working in mechanistic immunotherapy, exploring treatments that work by manipulating the structure of cells.
“I’ve always been interested in cells, but also mechanics, and how cells interact with forces,” Ann said. “I like this approach because it’s kind of new, and I think it’s very different from what you generally learn in biology, where everything is a series of chemical reactions. I really enjoy the interaction between the two fields.”
Support for Anne’s publications came from the Cornell Open Publishing Fund.