Team:Stuttgart/Description

Project Description Project Description

Inspiration

Inspirations from nature are the trickiest ones. Nature simply works. We as scientists try to find ways to use these mechanisms, which work in nature, to our advantage. That's how we became fascinated with one special animal living in nature.

As we all know, our planet gets increasingly hotter due to the fact, that more UV radiation reaches the earth. So, there is an urgent need to develop effective and enduring sun protection. Regarding other organisms, one of them has an outstanding ability to resist UV radiation. Tardigrades can survive not only in freezing conditions but moreover in a very hot environment. Their DNA gets protected by a protein called Dsup. Could Dsup be the key to creating a new way of sun protection?

The first admiration of the tardigrades came from the, at that time still, current Spektrum article (10/2020)[1], by talking about tardigrade species that are even more survivable than the already discovered tardigrades. The upcoming interest in these little living beings led us to read more about them through which we came across the tardigrade-unique protein called Dsup.

The main inspiration was found in the article “Extremotolerant tardigrade genome and improved radiotolerance of human cultured cells by tardigrade-unique protein”[2], emphasizing the phrase talking about the achievement where the scientist demonstrated that a tardigrade-unique DNA-associated protein suppresses X-ray-induced DNA damage by ~40 % and improves radiotolerance. Therefore, tardigrades could be a source of new protection mechanisms. In addition to our team members, the fascination of the tardigrade has also prompted other teams to research its superior survival mechanisms and apply them to problems in modern life. The little high-flyer has thus already been the main actor in five projects of iGEM teams.

Tardigrades are interesting organisms, which can be found all over the world. They can tolerate environmental fluctuations over a long period of time (for example survive several days without oxygen or defy UV radiation). To achieve these properties, tardigrades possess special proteins. One of them is the damage suppressor protein (Dsup), which protects the DNA of the organism from UV radiation-induced damage.

The protein protects the DNA by surrounding it like a shield. Due to these characteristics, the protein was used by different scientists, who successfully showed the transfection into Escherichia coli cells and HEK293 cells. With this modification, the cells were able to survive high radiation doses.

Through the unstopping increase of UV radiation reaching the earth due to climate change, the damage caused by UV radiation worsens every day. These damages include damaged DNA of organisms as well as damages in objects such as plastic surfaces. Why is it that UV radiation is permanently a threat to the DNA of most organisms? Well, if UV radiation hits DNA, the DNA must absorb the high energy photons, which leads to a fusion of neighbouring thymine and cytosine. Through this fusion, the genetic code does not any longer encode for the same enzyme or protein as it used to. Alternatively, radicals (reactive oxygen species, ROS) can be formed as a mechanism to cope with the high energy photons. In addition, gene expression and the immune system are altered. As a result of both, the cell is not able to produce basic needs for maintenance and damaged cells start to exist. In the long term, these mutations of the genetic material and cell changes can lead to cell death or in the worst case to the development of a cancer cell [5].

The Stuttgart iGEM-Team wants to use these properties within the Tardisun project. By transfecting the protein into eukaryotic cells, we want to improve the life cell imaging method. This method is widely used to observe the localization of proteins in biological processes. In this case, long exposure to light leads to Phototoxicity, which can be avoided, using Dsup. To observe potential changes, we like to perform the life cell imaging method to verify the benefit.

Within the Tardisun project, we would like to express and isolate the Dsup protein in Escherichia coli cells. The purified protein should be dispensed into a liquid. In this context, we want to find out if the absorbance properties are independent of the DNA protection function. The developed liquid could be used to protect other surfaces (e.g. skin or other UV sensible surfaces).

Our project aims to protect both materials such as plastic and one of the most important organs of humans, the skin, from the damage caused by UV radiation. If Dsup could be expressed in another organism besides tardigrades, would it shield foreign DNA as well? We want to create a new way of UV radiation protection. The aim is, to not only achieve protection of DNA in an organism but a way of shielding DNA during live-cell imaging. This would enable samples to endure longer while exposed to radiation.

Why is this project important to us?

UV radiation is carcinogenic and can cause many different types of skin cancer [3]. This needs to be prevented, both during summer vacations and at work. Already in Germany, an estimated 2.5 million workers are exposed to an increased risk of skin cancer due to their outdoor work [4].

Not only our cells but also all other materials exposed to UV radiation will be attacked and damaged. We want to protect plastic polymers and other substances from the sun’s rays with the help of DSUP in order to slow down the degradation. Thereby we want to extend their service life resulting in fewer required replacements. By doing so, less plastic will be produced, and the environment will be protected better.

[1] “Extrem-Lebewesen: Blaues Leuchten Schützt Bärtierchen Vor Strahlung - Spektrum Der Wissenschaft,” accessed October 19, 2021, https://www.spektrum.de/news/blaues-leuchten-schuetzt-baertierchen-vor-strahlung/1782371.

[2] Takuma Hashimoto et al., “Extremotolerant Tardigrade Genome and Improved Radiotolerance of Human Cultured Cells by Tardigrade-Unique Protein,” Nature Communications 7, no. 1 (September 20, 2016): 12808, https://doi.org/10.1038/ncomms12808.

[3] M. Ichihashi et all. (2003) UV-induced skin damage ()

[4] H. Drexler, P. Elsner & J. Schmitt (2015) UV-irradiation-induced skin cancer as a new occupational disease, https://link.springer.com/article/10.1007/s00105-015-3587-z

[5] Baljit Singh, Nisha Sharma (2007) Mechanistic implications of plastic degradation, https://www.sciencedirect.com/science/article/pii/S0141391007003539?casa_token=q4AqBStftXQAAAAA:5qiUeBYJbq7xTAI9fyQjPuUjfi1Hn_0CGvPxVr5W9QQBXrW_zN3OgcpXnhajA3KQ1f1iXTYQKf0