Dr. Corey Nislow is an associate professor in the Faculty of Pharmaceutical Sciences at UBC. His research combines biotechnology and genomics to address fundamental questions about the link between environment and gene function. This includes a collaboration with NASA examining the effects of microgravity and radiation on yeast cells by sending them to space. We sat down with Dr. Nislow to discuss how the project came about, and its implications for astronauts.
How did your collaboration with NASA begin?
The story of us getting involved with NASA began after the space shuttle Columbia disaster. It was revealed in retrospect that if a second shuttle was available on standby, the crew members could potentially have been rescued. So after their return to flight 2005 they started having a back up shuttle for every mission. But this meant that when they announced the closure of the program, they had a leftover shuttle. The decision was made to launch a last mission with the remaining shuttle, a skeleton crew of four members (rather than the normal eight), and as much science as they could fit.
But they needed science that was ready to go! Our lab had just started to explore how changing environment, including lowering oxygen, affects the interaction of genes and drugs in yeast. So looking at microgravity in space seemed like a good fit, and we sent up the yeast deletion collection, a set of over 6000 yeast mutants which we have exposed to over 10,000 different compounds.
What are these experiments testing?
The first thing we’re looking at is how microgravity and the environment of microgravity affects cells. You can imagine that if you’re a cell in microgravity, it’s not so much the microgravity that has a direct effect on your metabolism, but the effect of microgravity on your immediate environment, such as the generation of reactive oxygen species. Those reactive oxygen species will not diffuse away in the same way that they would in 1G on earth. Some people argue that this is not relevant on the scale of a single cell or microbe gravity effects are small. And although that may be true, the reality is that cells exist in a community, and the effects on the community are profound, or at least that’s what we are finding.
The second thing we’re doing is taking advantage of the fact that radiation exposure is quite a bit higher when you’re 220 miles up. Yeast is a premier organism for understanding the DNA damage response. So we’re looking for changes in radiation-induced DNA damage on station. Having said that, the International Space Station isn’t actually the best place to study radiation, because it’s not that severe, as compared to what will be experienced on a trip to Mars. To really get bombarded with radiation your options are either to get your experiment into high earth orbit or put it in a balloon above the Antarctic right in the Van Allen belt. We’re actually trying to figure out how to do the balloon experiment.
How long does each mission/experiment last?
Typically between 5 days and 30 days. We wanted to do a long term radiation experiment with NASA, but they told us that it was too big of a change so late in the game, and we should have asked a year before. Then when our plates came back from our 3rd mission on Space X, we opened the box and instead of the ten plates we sent to space, there were only five that made the trip home. They forgot to bring back the other five! So we got our 30 day and our 180 day exposure by accident. You can imagine that when NASA apologized for this incredible screw up, we were very understanding.
Have their been any setbacks?
We had one package of plates and experiments that were on SpaceX-6. I was watching the launch live and I’m describing to everyone in the room that at T+2’30’’ the first and second rocket stages separate. But suddenly we saw this very large fireball at 1’30’’. We lost our 50 thousand dollar experiment. What happened was that the liquid fuel mixed with the solid fuel in an inappropriate manner, and there was a total loss of mission. That was a setback!
What have been the most interesting findings so far?
There has previously been anecdotal evidence that cells experience an increased level of reactive oxygen species (ROS) in microgravity. This is fairly straight forward to detect in yeast. So we were able to show in untreated and drug treated cells that the environment on station in microgravity mimicked one in 1G where ROS had been artificially boosted. It may not be earth shattering, but it’s a robust confirmation that the cells on station either experience increased levels of ROS, fail to rid themselves of ROS, or to detoxify it. This is where our next set of experiments are going. You can imagine, if this ROS accumulation holds true for metazoans, that it could be pretty profound. The biggest reported physiological effects on crew members to date are muscle redistribution, fat redistribution, bone density loss, and ocular pressure. These are all fairly straightforward to conceptualize, but there may be fundamental underlying cellular effects such as ROS generation.
How does it feel to know that your very own research has been to space?
This will show you what a complete nerd I am! When our very first yeast growing device came back from space, I ordered a kit for embedding material in clear electron microscopy resin, mixed it up, laid the device in it, and cured it. Then I gave it to my father-in-law who is a Nobel laureate. I thought I would finally have done something that would impress him. He wasn’t. But I was still excited! Whenever a mission comes back, I make sure to continue to take something and cure it in electron microscopy resin for posterity. Insects in amber will last hundreds of years, so maybe these will as well!
Do you plan to continue sending experiments to space, and if so, how will the experiments change?
The next thing that we would like to do is to sequence the transcriptome of crew members in as large a sample size as possible over the course of a mission, and see if we can detect any biomarkers that might be able to help us figure out things that we can’t figure out with yeast. This has been done in the past with N-point PCR and northern blots, but no one has done a well controlled longitudinal RNA-seq experiment of all crew members. I plan to do whatever it takes to make this experiment feasible, even if it means using myself as a test subject for transcriptome analysis on NASA’s parabolic jet (affectionately known as the vomit comet).
Thank you very much for your time Dr. Nislow. It’s incredible to know that this exciting research is happening here in Vancouver!
Click here to read Dr. Nislow’s first paper on this project.
