Scientists are tampering with tardigrade DNA to find out how they get their superpowers

Scientists are tampering with tardigrade DNA to find out how they get their superpowers


And as we learn more about how tardigrades can survive extreme conditions, this knowledge could be applied to biomedical technologies, such as the preservation and transport of human organs.

Tardigrades are virtually indestructible. You can expose them to extreme heat, freeze them, place them in a vacuum, or even completely dry them out: it doesn’t seem to affect them much. These extraordinary properties make tardigrades a fascinating subject for researchers, who are interested in unraveling their secrets not only out of curiosity, but also because of the possible applications. And in a new study researchers focused on the core of their bizarre properties: the genome.

Genome
So we know that some tardigrade species are extremely and unusually resistant to conditions that would be fatal to most other life forms. However, the genetic basis of this special ability remains a mystery. “To understand tardigrades’ superpowers, we first need to understand how their genes work,” explains researcher Takekazu Kunieda. “My team and I have developed a method to edit – add, delete or overwrite – genes, as you would with computer data, in the highly tolerant tardigrade species Ramazzottius varieornatus. This now allows us to study the genetic properties of tardigrades, similar to the way we do with established laboratory animals such as fruit flies or roundworms.”

CRISPR
The team applied a recently developed technique called direct parental CRISPR (DIPA-CRISPR), based on the well-known CRISPR gene editing technique (see box). This method acts as a genetic scalpel to cut and modify specific genes more precisely than ever. DIPA-CRISPR has the ability to influence the genome of offspring of a target organism and has previously worked effectively in insects. Now the researchers applied this technique for the first time to another organism. And with success. Ramazzottius varieornatusan all-female species that reproduces asexually, consistently produced offspring with two identical copies of the same edited genes, making this species ideal for DIPA-CRISPR.

What is CRISPR again?
CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats and is part of a particularly efficient defense mechanism that bacteria use in the fight against tiny virus particles (also called bacteriophages). These virus particles can literally destroy a bacterium. They do this as follows: they cling to the bacterial cell and pump their DNA in, after which they use the bacteria to copy themselves thousands of times. Once this is successful, the virus particles burst the bacteria and the thousands of copies start looking for other bacteria in which they can repeat that trick again. Fortunately for the bacterium, it is not defenseless in this entire scenario; it has a defense mechanism called CRISPR-Cas, which consists of two parts. One part hunts for enemy DNA and the other cuts that DNA. Years ago, researchers came to the brilliant conclusion that this bacterial defense mechanism can also be used to switch off specific genes in living cells. Or detect ‘wrong’ pieces of DNA, cut them out and replace them with an alternative piece of DNA. In short: CRISPR systems offer us a relatively easy, fast and very precise way to edit DNA. And not only DNA from viruses, but also in plants, animals and people. It is expected that CRISPR can be used in the future to combat genetic diseases, but also retroviruses that reside in the DNA, such as HIV.

In short, using the CRISPR technique, researchers have now tampered with the tardigrade’s DNA. And that immediately produced genetically modified offspring. “We just had to inject the CRISPR-programmed tools, which targeted specific genes for deletion, into a parent’s body to produce modified offspring,” explains researcher Koyuki Kondo. “We were also able to obtain genetically modified offspring by adding additional DNA fragments via injection. This allows us to accurately edit tardigrade genomes. In this way we can, for example, determine how individual genes are expressed or what specific functions these genes fulfill.”

A tardigrade receives a dose of CRISPR tools to alter one of its genes, as well as those of the eggs it will soon produce. Image: 2024 Tokiko Saigo et al.

Superpower
By editing specific tardigrade genes, researchers can study which of these genes are responsible for tardigrade resilience and how exactly this resilience works. And the most remarkable ‘superpower’ of Ramazzottius varieornatus, is that this species can survive extreme dehydration for long periods of time. This may be partly attributed to a specific gel protein in their cells. And that has interesting implications. For example, Kunieda and other tardigrade researchers believe it is worth studying whether an entire human organ can ever be successfully dehydrated and rehydrated without leading to degradation. If this proves feasible, it could have a revolutionary impact on the way organs are donated, transported and used during surgical procedures to save lives.

All in all, researchers have succeeded in editing the genome of tardigrades. And that marks a major breakthrough in our understanding of the genetic basis of their remarkable survivability. At the same time, this may sound like ‘science fiction’ and manipulation to some. “I understand that some people are concerned about gene editing,” Kunieda says. “But we conducted the gene editing experiments under strictly controlled conditions and stored the genetically edited organisms safely in a locked compartment. CRISPR could be an extremely powerful tool to better understand life and support practical applications that can bring about positive change in the world. Tardigrades not only provide insight into potential medical breakthroughs, but their remarkable properties also tell a fascinating evolutionary story. We hope to explore this story further by comparing their genomes with those of closely related organisms, using our new DIPA-CRISPR technique.”