Increasing Human Tolerance to Radiation - Lessons from Extremophile DNA

Tardigrades, small aquatic animals, are one of the most resilient organisms known to man. They are capable of surviving under extreme physical stress, such as:

• exposure to temperatures ranging from - 273 degrees C to 100 degrees C
• exposure to high doses radiation
• exposure to outer space
• exposure to extreme pressure
• immersion in organic solvents
• etc.

It is therefore obvious to assume that these small organisms are of interest to the research community; and to my personal interest as well. Scientists from a Japanese university recently published a paper in Nature:

Extremotolerant tardigrade genome and improved radiotolerance of human cultured cells by tardigrade-unique protein

They wanted to see how human cultured cells respond to DNA damage in the presence of a tardigrade-unique DNA-associated protein. Here I'm going to discuss some of their findings.

---

Insights from Tardigrade Genome Analysis

In their study they used one of the most stress-tolerant species of tardigrades, Ramazzottius varieornatus.

• (a) in normal conditions - hydrated
• (b) in extreme conditions - desiccated
• (c) gene repertoire of the species

In the genome and transcriptome analysis of these tardigrades compared to other organisms, researchers found:

• increase in the transcription of catalase gene, which codes for an antioxidant enzyme (better coping with oxidative stress during desiccation)
• increase in the repertoire of superoxide dismutase family - SODs (16 vs. <10 in most metazoans) - regulates superoxide radicals - provides protection against oxidation damage in desiccation
• increase in MRE11 genes (4 vs. 1 in most animals) - role in DNA damage repair.

"Magenta indicates genes absent in the tardigrade genome and green indicates retained genes. The interconnected eight genes mediating environmental stress stimuli to downregulate mTORC1 were selectively lost, whereas all components involved in sensing and mediating physiologic demands were present." [source]

Aside of these genes that are present in other organisms - including humans - (but are less expressed), researchers also found higher expression of tardigrade-unique genes, one of them being Dsup generically called like that due to its DNA damage suppression activity:

"Dsup protein is a prominent example of tardigrade-unique abundant proteins involved in tolerability and is, to our knowledge, the first DNA-associating protein demonstrated to protect DNA and improve the radiotolerance of cultured animal cells."

To determine if it could be efficacious in other cells and organisms they established a cell culture line HEK293 to express Dsup. They started from the hypothesis that association of Dsup proteins with nuclear DNA may help protect DNA from irradiation damage.

They exposed the cells to X-ray irradiation that is known to induce both single and double strand DNA breaks (SSB, DSB).

What you see above:

- (a) The effects of Dsup on SSBs by 10Gy X-ray irradiation in alkaline comet assays.
- (b) The effects of Dsup on SSBs caused by hydrogen peroxide (H2O2) treatment in alkaline comet assays.
- (c) The effects of Dsup on DSBs by 5Gy X-ray irradiation in neutral comet assays.

In short, what they found was that:

• Dsup suppresses X-ray induced SSB and DSB in human cells
• Dsup improves viability of human cells exposed to irradiation:

"Almost all irradiated untransfected cells had an abnormal round shape and were mostly detached from the culture dish, typical characteristics of dead cells. In contrast, many irradiated Dsup-expressing cells had a normal morphology and attached to the culture dishes, suggesting that these cells retained the characteristics of live adherent cells and perhaps even had proliferative ability."

*- irradiated untransfected - normal cells that do not express Dsup

---

Ending Thoughts

Findings like the ones in this study are very exciting especially when considering the relative easiness of doing genomic engineering today. Leveraging upon the extreme resilience of other organisms may provide beneficial applications to humans in the not so distant future; but I should remain more conservative in my arguments. Hashimoto et. al (2016) conclude their study by saying:

"The genome sequence and gene repertoire of the extremotolerant tardigrade revealed in this study provide a treasury of genes to improve or augment the tolerant ability in stress-sensitive animal cells."

I'll end leaving you with a video release from the study - a video showing R. varieornatus going into/out of anhydrobiosis (reversible ametabolic state where they dehydrate):

---

To stay in touch with me, follow @cristi

Study: [Hashimoto, T. et al. Extremotolerant tardigrade genome and improved radiotolerance of human cultured cells by tardigrade-unique protein. Nat. Commun. 7:12808 doi:10.1038/ncomms12808 (2016)]

Credits for Images: [Hashimoto and colleagues via Nature].

#extreme #science #research

---

Cristi Vlad, Self-Experimenter and Author