Genomic Radiation Damage Protection with Tardigrades!

Michael Trịnh
8 min readOct 22, 2018

Radiation is loose energy that traverses everywhere in our universe, and it’s very prevalent on Earth. For decades, we have liked numerous types of radiation and adverse effects of exposure to be visibly damaging to our genetic material.

Radiation and the Tardigrade

From helping prevent cancer and other genetic diseases, to allowing humans to explore the depths of space without deadly side effects; reducing biological radiation damage in human cells would allow us to solve large-scale problems across countless industries and disciplines.

(Heads up): in order to understand how radiation works and how it interacts with our DNA and even our spaceship materials, I recommend reading my previous article first.

Although seemingly a tough challenge for us, mother nature has already found a way to protect genetic material from radiation damage, and us curious humans are just starting to find out how!

Meet the Tardigrade, little creatures like this may hold some incredible, natural solutions to our radiation problems. Although seemingly an obscure study of a small creature on the surface, what really sparked interest in me was that one of these solutions were also artificially expressed in human cells.

PC: Washington Post

The tardigrade is the Earth’s most resilient animal that we know of to date, and for good reason! Many Tardigrade subspecies hold various gene-strengthening tools which can allow us to effectively defend DNA against radiation. These tools range from crucial antioxidants for reactive toxins, to special DNA repairing proteins that Tardigrades exhibit in large volume.

Desiccation and Tardigrade Superpowers!

Tardigrades can go into a state of specialized dehydration (desiccation), which is where their famous survival traits kick in. This is where we can observe some of their biological defense tools at work.

Contrary to popular belief, tardigrades at their normal, non-dried body state are relatively fragile. It is when they undergo a specialized body-wide dehydration called desiccation, where their incredible survival traits kick in!

Tardigrades at hydrated state (Top) to desiccated state (Bottom)

In an effort to protect their cells and DNA from critical damage via external radiation or internal toxins, many Tardigrade species can desiccate their bodies to extreme extents. This state allows tardigrades to protect their cell contents, body structures, and DNA in the toughest conditions, emerging physically healthy once the environment changes in a rehydrated form.

And when I say “to extreme extents”, I mean tardigrades can reduce their body water levels to 1% of their original volume, and bring down their metabolic activity down to 0.01% of its original levels!

Not only that, but these incredible creatures can on average, maintain this state for 5 years! Additionally, many cases now show tardigrades surviving up to 10 years in this state.

That’s 5–10 years of no water and food, all while being in extreme environments which most creatures cannot survive. It’s while in this state where our tardigrades can survive brutal temperature extremes such as being in liquid nitrogen, boiling water, and even experiencing radiation doses at levels 200X greater than what we humans are able to deal with.

Here we are gonna explore biological tactics that tardigrades use to make their DNA incomparably stronger than our own, which attribute in part to their physical toughness and resiliency to radiation exposure!

Radical Damage to DNA and Antioxidants

When certain types of ionizing radiation hit water in your body, it can turn good old friendly H2O into an extremely reactive molecule: the free radical. This toxin typically spells trouble in any biological environment it pops up in, although we can use these molecules to detoxify water.

Free radicals such as Reactive Oxygen Species (ROS’s) are uncharged Oxygen-containing molecules with an unpaired electron, caused by an oxidation reaction. Radicals will seek anywhere to steal an electron from, as quickly as possible. Usually the abundant source of electrons is our negatively charged DNA, so this becomes the prime target for such formed radicals.

When these radicals grab an electron from our DNA, it compromises the structure, leading to mis-translation of proteins, single/double strand breaks, etc.

All these effects of radical oxidation can be precursors to cancer tumor development, and some instances of such DNA damage are irreparable. We know that in mammals, Hydroxyl free radicals generated via the irradiation of body water makes up for about 2/3 of known DNA radiation damage. This is likely one reason as to why animals that desiccate and shed most of their body water like Tardigrades, appear so resistant to radiation damage.

Although the process of desiccation will reduce the risk of free radical damage significantly, it still isn’t quite enough for the Tardigrade. Antioxidants are special types of enzymes which have a main job of quickly inhibiting oxidation reactions, and they work to stop radicals from forming in their tracks.

All animals express different species of antioxidants at varying amounts, but Tardigrades take them to a next level!

While in their hydrated and desiccated states, tardigrades are found to have comparable levels of dismutases and catalases, which are antioxidants responsible for dismantling Oxygen Radicals and Hydrogen Peroxide (H2O2) respectively.

By acting as an enzyme which speeds up and accommodates the breaking down of the Superoxide Oxygen Radical, dismutases such as glutathione and superoxide dismutase indirectly break down these dangerous toxins into harmless Oxygen gas (O2).

When the tardigrades enter their desiccated state, the number of dismutases experience a noticeable increase. We think this could be to help preserve the DNA of the desiccated Tardigrades from toxic damage, and what could be one of the players in allowing the Tardigrades to stay dehydrated so long.

The “Dsup” Protein (DNA Repair)

Antioxidants are one thing: we all have them, and although they are one part of the reason why Tardigrades have their resiliency, they aren’t by any means the star of our show.

Researchers in Japan did a study into how desiccated Tardigrades have the ability to survive extremely high doses of radiation compared to most other organisms’ tolerance.

When radiation hits your body, we often worry about the ionizing damage done to your genes as a result. The researchers noted that radioactively tolerant animals like Tardigrades, Bdelloid Rotifers and Sleeping Chironomoids, all experience relatively similar degrees of DNA damage upon irradiation as most other animals do. Keep in mind that those creatures all have significantly higher gamma ray resiliency than us humans.

PC: CC0 Public Domain

However when the ability to repair DNA quickly and efficiently is weakened in these organisms, their overall radiation resistance is compromised. This implies that the majority of work being done on the end of natural radiation resistance, comes in the form of effective DNA protection and repair.

This is where Tardigrade-specific proteins for DNA support may set them apart from the rest of us…

The researchers came across a Tardigrade-specific DNA support protein, which they dubbed “Damage Suppressor” or Dsup. They are now linking this protein to many Tardigrade species’ immensely high radiation tolerance during their hydrated and desiccated states. This sets Tardigrades apart from other radioactively-tolerant creatures who may have high radiation resistance while desiccated, but much less when in their normal hydrated state.

Dsup proteins do not help the process of DNA repair itself, but rather act as a biological bulwark for DNA. This prevents damages like single and double strand breaks from occurring upon initial irradiation of the genome, by protecting the DNA from radical species that would ionize it.

Dsup in Human Cells!

When identified, scientists cultured a human cell line that expressed the Dsup protein in it, and then blasted it with X-Rays.

Cells that expressed Dsup had around 40–50% greater resiliency against irradiation damage than Dsup-free cells. The Dsup-expressing cells were also much more resilient specifically from Hydrogen Peroxide ROS damage, compared to their Non-Dsup counterparts.

While radioactively damaged human cells lost their ability to divide and recover their populations, their Dsup-expressing counterparts did not experience the same issues.

Dsup does this protection likely by binding to one end of themselves (N-terminal tail) to the DNA double helix, where it performs its role job of shielding the DNA and possibly detoxifying incoming radicals.

This essentially means that Dsup works to protect the DNA directly against radiation damage, as well as against indirect damage from radiation (formation of ROS in irradiated water). Human cells expressing Dsup could take on higher radiation doses than the human limit for radiation exposure, and were observed to still ably reproduce overtime.

Dsup is what we believe to be the Tardigrades’ main secret weapons for radiation resistance, as we have not seen this protein expressed in any other type of organism as of yet!

Key Takeaways

To sum things up for this study into natural radiation defense of DNA, here’s what you need to know:

  1. Radiation such as Ionizing radiation can directly or indirectly damage DNA, with serious consequences.
  2. Small microorganisms like Tardigrades have an arsenal of radiation-protection tools which allow them to survive radiation doses that are magnitudes higher than our own limits as humans.
  3. Some of these tools include antioxidants, and a DNA-binding protein called Dsup, which likely shields the strand from radiation and toxins.
PC: National Geographic/Youtube

For the foreseeable future we will be studying nature’s innovative works, and using them from our own novel solutions. This could even go as far as possibly applying Dsup into more specialized human cells! As everything becomes more cross-discipline across modern industry and STEM innovation, we’re gonna see biology applied to problems where we never expected before.

I will be covering some of these applications and doing some interesting hands-on work into it as well later in the coming weeks, which I will be sharing with all of you. Stay tuned!

Sources

  1. DNA Protection Protein, a Novel Mechanism of Radiation Tolerance: Lessons from Tardigrades. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5492148/
  2. Dsup- Damage Suppressor Protein https://www.uniprot.org/uniprot/P0DOW4

Images

  1. https://www.washingtonpost.com/video/national/health-science/meet-the-tardigrade-the-animal-that-will-outlive-us-all/2017/07/14/4b921e54-68ae-11e7-94ab-5b1f0ff459df_video.html?utm_term=.67b4add07eba
  2. https://www.haleo.co.uk/the-body/antioxidants/,
  3. https://www.peakendurancesport.com/nutrition-for-endurance-athletes/dietary-basics/antioxidant-nutrition-best-practice-guidelines-maximum-performance/
  4. CC0 Public Domain
  5. DNA Protection Protein, a Novel Mechanism of Radiation Tolerance: Lessons from Tardigrades. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5492148/
  6. National Geographic/YouTube

--

--

Michael Trịnh

Undergraduate builder & researcher @UofT in the crossroads of bioinformatics, immunology, and genome engineering.