ASU Biodesign Institute researchers are using the unique conditions of spaceflight to examine how cells remain healthy or succumb to disease, particularly in the face of stress or damage. Their experiment will be launched into low earth orbit on April 5 aboard the space shuttle Discovery on mission STS-131.
The team hopes to provide fundamental new insight into the infectious disease process, and further undestanding of other progressive diseases, including immune disorders and cancer. The Results of the current study will also be used to help mitigate infectious disease risks to the crew, who are particularly vulnerable to infection, due to reduced immune function during spaceflight missions.
"The key to this research," said ASU researcher Cherly Nickerson, "is the novel way that cells adapt and respond to the unique microgravity environment of spaceflight. In response to microgravity, cells exhibit important biological characteristics that are directly relevant to human health and disease, including changes in immune function, stress responses, and virulence (infectious disease potential) that are not observed using traditional experimental approaches."
The current mission marks the first time that human cells will undergo infection by a pathogen in spaceflight. Specifically, this thirteen day experiment, called STL-Immune, will characterize the effect of microgravity on intestinal cellular responses before and after infection with the food-borne pathogen, Salmonella typhimurium. Results of this study will be analyzed in a collaborative effort between Nickerson's lab and that of her co-investigator Mark Ott, a researcher at NASA's Johnson Space Center, and his graduate student, Sarah Castro.
The goals of these experiments are twofold: a) to better understand the effect of spaceflight on human cells before and after infection with an invasive bacterial pathogen—information of vital importance for ensuring the safety of astronauts, and b) to gain insight into responses of human and pathogenic cells in their customary environment within the human body on Earth. These conditions, Nickerson explains, can sometimes bear intriguing similarities to those observed during spaceflight, though this effect is often masked by gravity in conventional, Earth-based experiments.
Disease-causing bacteria like Salmonella are capable of keenly sensing the environmental conditions they encounter during infection in their human or animal hosts, adjusting their virulence as conditions dictate. As they infect their hosts, bacteria use a battery of options to dodge attempts to destroy them. Nickerson's previous work showed that bacteria can use the Hfq protein to regulate their pathogenic responses to fluid shear. The Hfq protein is highly conserved in bacteria, meaning it is found among a wide array of species, and plays an essential role in the infection process.
Interestingly, human cells have their own version of the bacterial Hfq protein, call Sm proteins, which are involved in cellular differentiation and responses to stress, immune system function, and the production of tumors. The group hopes to determine if the Sm proteins also act as response regulators during spaceflight, like the Hfq protein does in bacteria.
A more thorough understanding of the way pathogens and human cells interact in space may pave the way to new vaccines and therapeutics for a broad range of infectious diseases, as well as other afflictions affecting human populations. Additionally, the results will be used to fine-tune protocols affecting astronauts, helping to ensure they don't fall victim to heightened microbial virulence.
"While studying cells using traditional experimental conditions in the laboratory has taught us an enormous amount about how cells behave normally or develop disease," Nickerson said, "we are starting to realize just how much we've missed using these conventional approaches. Our work using the spaceflight platform for such studies has and will continue to advance our fundamental understanding of the disease process in cells and could lead to major advancements in human health."
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