SPACE IS SICK
A study led by U of O professor Odette Laneuville (PhD) suggests that astronauts have a weakened immune system while in the extreme conditions of space. The Fulcrum spoke with Laneuville, a researcher and expert in the biology of rehabilitation, to discuss her study in more detail.
She has done extensive work with fellow U of O professor Guy Trudel on rehabilitation and joint mobility, eventually leading to a study with the Canadian European Space Agencies on the effects of microgravity on bedrest and bone marrow composition.
Laneuville explained that leukocytes are simply another name for white blood cells. For the purpose of her research, they use these cells because they have a nucleus, and thus a genome, that can be transcribed.
To understand what transcriptomes are, consider the genome as the library and the transcriptome as a cookbook with a whole bunch of recipes. This cookbook, as Laneuville explained, “you cannot take it out…all you can do is photocopy pages or recipes.” In this case, the recipes are the RNA sequence that play a role in cell activity, and the transcriptome response in leukocytes.
She continued, “a recipe is a transcript or a gene being transcribed. Once they’ve left the library, this is equivalent to a cell sending transcripts outside the nucleus into the cell cytoplasm where they’re going to be translated.”
She is interested in looking at all those recipes that are copied from the genome, and determining their nature and how many copies are present. This is done by looking at different time points and identifying copies including those that happened to be immune-related genes.
Methodology: Separation, extraction, sequencing, and more!
Astronauts with missions to the International Space Station (ISS) had ten blood samples collected across the three periods of the study: one pre-flight (PF), four while in-flight (IF) on the ISS, and five after returning to Earth (R). This is to ensure they had all the at each time point in order to compare them.
Collecting blood on Earth with medical staff takes around two minutes. However, in space, it takes 40 minutes. Laneuville explained this task goes from simple to rather precarious — they need to secure the sample and the needle (or else it will float away), ensuring not a single drop leaks, not to mention the added task of spinning it down (centrifuging) and freezing.
“They have to be extremely careful to take their blood, because there’s no nurse, there’s no physician, they’re on their own,” she said.
The centrifuge is what allowed astronauts to separate the white blood cells from other cells in our blood (red blood cells, platelets, and platelets).
“Since red blood cells have no nucleus during the spinning down process, they’ll be found packed below a gel located at the bottom of the test tube. On top of the gel, you’ll have your white blood cells which are too big to get through the gel and the plasma because the speed of centrifugation is not fast enough.” added Laneuville.
Once the frozen samples are back on Earth, they’ll be thawed and then resuspended in order for the white blood cells to be isolated and RNA extracted.
Following separation and extraction, she continued with sequencing or isolation of the transcripts (RNA or nucleic acid) of the white blood cells resulting in two clusters. She went into further detail to explain the analysis of the sequencing results she performed.
Genes in the first cluster which code for proteins related to immunity were dialled down when reaching space and back up when returning to Earth, while genes in the second tied to cellular structure and function followed the opposite pattern.
The results
Let’s consider all the transcripts at each time point (PF, IF, R). “[Since] we knew the composition, we could now compare them, and what we noticed was that the immune related genes were downregulated to 112, meaning fewer copies were made while in space. Upon returning to Earth, the number of immune related genes went up (upregulation) to 135, and eventually back to what we had at the baseline with zero genes differentially expressed.”
When they compared the genes changing when going to space to those changing when returning from space they found most were the same gene and many regulating immune functions.
This is interesting because it tells researchers when to look for changes during spaceflight. Based on the results of this study, most of the changes are occurring during the transition from Earth to space and from space back to Earth. However, while they’re in space there’s very little change in expression.
What causes gene expression changes?
When asked to elaborate on what about space causes changes in gene expression, Laneuville responded, “I can say with confidence it would be [the very fact] they’re in space. In other words, I believe it’s the microgravity component that contributes to the change in the profile of gene expression.” She knows microgravity is important for the transcriptome response since her group published similar findings from an Earth model of microgravity in which they studied participants to a bed rest study.
“However, I cannot eliminate other factors such as cosmic radiation, disturbed sleep cycle, increased stress, and a different diet. There’s a lot left to understand and my approach to look at gene expression will generate some interesting hypotheses, but broadly we should see genetic and physiological changes coincide, [though] it’s not a direct cause-effect relationship.”
What’s the story with herpesvirus?
According to Laneuville, the changes of immune-related genes while transiting to and from space and then back to baseline is important because the results are in agreement with clinical evidence of a phenomenon known as the reactivation of latent viruses.
An example of one of these viruses is chickenpox (a member of the herpesvirus family) and individuals with it cannot overcome that infection entirely. Rather, it will remain dormant with our nerves along the spine until later in life when we encounter a stress that can trigger a reactivation of the dormant virus and subsequently give rise to shingles. This is what some astronauts can expect to face (reactivation of latent viruses and evolution towards severe symptoms) — nothing says welcome back like getting shingles.
Although few astronauts develop symptoms while in space or come home with symptoms such as skin lesions, Laneuville explained it is, “not necessarily to the point of inducing severe symptoms. Longer spaceflight needed to reach Mars might lead to more severe symptoms. It also means that an individual can be contagious when returning from space.”
Getting shingles in space opens up a whole can of worms, since access to doctors and medications you might need to control the infection could be very limited.
According to Laneuville’s discoveries, the reduction in immune-related genes was consistent with the reactivation of those latent viruses while in space and within a few weeks after returning to Earth. In addition, when back on Earth it was observed that immune genes returned to pre-flight levels of expression and correlates to resolving those infections.
For those interested in learning more about Laneuville’s research visit her U of O profile here.
