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Shuttle up for some genomics in space

Space. A silent vacuum beyond the upper limits of Earth’s atmosphere, home to billions of galaxies within our universe. A place almost incomprehensible to the human brain. Amongst it, orbits the international space station (ISS), the largest ever crewed object in space. First launched in 1998, the ISS has provided a key platform for scientific research. Luckily for us, the study of genetics on earth is just as important in space! Here, we explore some of the interesting and revolutionary genetic studies undertaken in space. So, shuttle up.

The Kelly twins

For decades, twin studies have been a fundamental tool for genomics. As of April 9th 2020, a total of 566 people from 41 countries have gone into space. Long-duration (>300 days) missions are typically rare. However, future plans for humans to go to Mars and beyond will require long-duration missions. As a result, it is imperative that researchers undertake comprehensive studies assessing the impact of long-duration spaceflight on the human body, brain and overall physiology.

To explore this, NASA monitored one monozygotic twin (Scott Kelly) before, during and after a 1-year mission onboard the ISS. The other twin (Mark Kelly) served as a genetically-matched ground control. NASA began this integrated multi-omics, molecular, physiological and behavioural longitudinal analysis in 2015 and conducted it over a total of 25 months.

NASA’s longitudinal assessments revealed specific spaceflight changes. These included decreased body mass, telomere elongation, genome instability, carotid artery distension, altered ocular structure, transcriptional and metabolic changes, DNA methylation changes in immune and oxidative stress-related pathways, microbiota alterations and some cognitive decline postflight. Despite average telomere length, global gene expression and microbiota alterations returning to near pre-flight levels within 6 months, the team observed increased numbers of short telomeres and disrupted expression of some genes.

The majority of biological and human health variables remained stable or returned to baseline after Scott’s 340-day space mission. Overall, this data suggests that human health can mostly be sustained during spaceflight. Most importantly, this study has provided insight into pathways and mechanisms that may be vulnerable to spaceflight. As a result, these findings serve as a guide for targeted countermeasures or monitoring during future missions. 

Telomeres

The key question everyone was interested in when Scott returned to Earth was whether space made him younger or older? Telomeres are repetitive regions of DNA at the ends of chromosomes. During DNA replication, telomeres shorten, in part because of the end replication problem. Telomere shortening is associated with ageing, mortality and age-related diseases, such as cardiovascular disease.

Researchers originally hypothesised that the high background radiation in space would accelerate telomere shortening and ageing. However, they surprisingly found that Scott’s telomeres in his white blood cells got longer while in space. Notably, Scott’s telomere length shorted rapidly upon his return to Earth and stabilised to near pre-flight averages within months. Additionally, there were substantially decreased numbers of telomeres detected, suggesting persistent telomere loss and/or increased numbers of critically short telomeres. This shift in telomere length supports accumulating evidence of telomere length as a robust biomarker for ageing and age-related diseases. As it can inform overall health, monitoring telomere length dynamics represents an important element of health evaluation and potential long-term risk for future astronauts.

Research on telomeres will continue in NASA’s One-Year Mission Project. This project involves studying 10 astronauts on one-year missions, 10 on six-month missions and 10 on trips from two to three months at a time. During these missions, health data will be collected and compared with people on the ground who are in isolation for the same period of time.

Susan Bailey, Professor of Radiation Cancer Biology and Oncology, Colorado State University, explained:

“We’re trying to determine if it is indeed something specific about space flight that is causing the changes we’ve seen.”

Increased radiation

Exposure to space radiation represents a serious potential long-term threat to the health of astronauts. This is because the amount of radiation exposure accumulates during their time in space. Estimates indicate that astronauts are exposed to ionising radiation with effective doses which range from 50 to 2,000 mSv. Three chest x-rays are equivalent to 1mSv of ionising radiation. Therefore, astronauts’ exposure is like having 150 to 6,000 chest x-rays.

Radiation exposure induces various biological effects, particularly DNA damage. Double-stranded DNA breaks are the most severe type of lesion. While organisms have DNA damage repair pathways, large amounts of damage can result in cell death, cellular senescence and tumourigenesis. In recent years, NASA have been exploring the risks of radiation to the CNS. Although the brain is a largely radioresistant organ, ground-based animal studies indicate that space radiation can alter neuronal tissue and neuronal functions, e.g. synaptic transmission.

Excitingly, last year, astronauts aboard the ISS successfully edited DNA for the first time using CRISPR/Cas9 technology. The Genes in Space-6 experiment, which is still underway, aims to explore how space radiation damages DNA and how cells repair that damage in microgravity. The astronauts used CRISPR/Cas9 to induce damage to the DNA of cells of the yeast Saccharomyces cerevisiae. After allowing time for repair, the astronauts aim to extract the DNA and sequence it using the MinION to determine whether the yeast repair mechanisms restored the DNA to its original order or introduced errors. The team expect the experiment to finish later this month.

Emily Gleason, one of the investigators, stated:

“The damage actually happens on the space station and the analysis also happens in space.

We want to understand if DNA repair methods are different in space than on Earth.”

To infinity and beyond

Our understanding of the universe is limited. Therefore, the possibilities of genetic research are endless. Environmental factors have a large impact on DNA and the living environment in outer space is extremely challenging to astronauts. Radiation exposure management and radiation protection are critical for future missions. Experts are hopeful that in the future the development of various radiation protection agents will progress. Additionally, exploring the mechanisms behind radioresistant organisms may aid in the development of novel technologies that could alleviate biological damage caused by radiation. Importantly, utilising available astronaut data, in particular that of long-duration mission crew members, should be beneficial.

Genomics in space will not only provide insight into health and life on earth but will be vital for future explorations to Mars. Think about how many discoveries occur on earth every day; now imagine how many more are waiting for us to discover in the place we call space!

Image credit: By macrovector – www.freepik.com


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Genomics / Space / Telomeres

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