Describe how and why you chose your iGEM project.
Describe how and why you chose your iGEM project.
Please see the 2024 Medals Page for more information.
UV radiation poses a threat to many populations, from astronauts to marine organisms, in the form of DNA damage in cells. The primary sources of UV radiation are the sun and artificial sources such as tanning beds, mercury-vapor lighting, and certain types of lasers. UV radiation is divided into three types based on wavelength: UVA, UVB, and UVC. Among these, UVA (320-400 nm) and UVB (290-320 nm) reach the Earth's surface, while UVC (100-290 nm) is absorbed by the ozone layer and does not penetrate the atmosphere. When astronauts are in space, there is no atmosphere to protect them from the UVC, posing an immediate threat to humans for space exploration [1].
The UV radiation may then cause DNA damage, which could lead to harmful mutations that interfere with normal cellular processes [5]. The problem of UV radiation is particularly common and severe in regions with high sun exposure, such as equatorial zones and areas with reduced ozone concentration. Ozone depletion has exacerbated the problem, leading to increased UVB levels, which are more biologically harmful than UVA. This increase in UV radiation poses significant health risks, including skin cancer, cataracts, and immune system suppression. Skin cancer, particularly melanoma, has seen rising incidence rates globally, correlating with increased UV exposure [2]. Non-melanoma skin cancers, such as basal cell carcinoma and squamous cell carcinoma, are also prevalent and linked to cumulative UV exposure [3].
Apart from human health, UV radiation affects ecosystems, particularly marine life. Phytoplankton, which forms the base of the aquatic food web, are susceptible to UV-induced damage, leading to potential disruptions in marine biodiversity and food resources. Terrestrial ecosystems are not immune, as UV radiation can affect plant growth, development, and photosynthesis, ultimately impacting crop yields and food security [4].
Preventive measures have primarily focused on minimizing exposure to harmful UV rays. Sunscreen formulations, which contain UV-filtering compounds, represent a widely adopted approach to protect human skin. Advances in sunscreen technology have led to the development of broad-spectrum formulations that protect against both UVA and UVB radiation. These formulations typically contain organic compounds like oxybenzone and avobenzone, as well as inorganic filters like zinc oxide and titanium dioxide [6]. Public health campaigns emphasizing the importance of sunscreen use, protective clothing, and shade have been instrumental in reducing UV-related health risks [7].
In the field of material science, UV-stabilizing additives have been incorporated into polymers and coatings to enhance their resistance to UV-induced degradation. These additives, such as hindered amine light stabilizers (HALS) and UV absorbers, work by scavenging free radicals and absorbing UV radiation, respectively [8]. The automotive and construction industries have particularly benefited from these advancements, as UV-stabilized materials demonstrate prolonged durability and aesthetic preservation under outdoor exposure.
Biological approaches have also been explored, particularly in the context of DNA repair mechanisms. The discovery of photolyases, enzymes that repair UV-induced DNA damage using light energy, has opened avenues for biotechnological applications. Photolyase-based treatments, although still in experimental stages, hold promise for mitigating UV-induced genetic damage in cells [9].
For our project, we decided to focus on maximizing the ability of photolyase to repair common types of DNA damage, particularly cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4) photoproducts, within human skin cells. We plan to combine a cell penetrating peptide (specifically the TAT peptide from the HIV virus), a nuclear localization signal (from the SV40 Large T-antigen), and either a 6-4 photolyase protein (from Arabidopsis thaliana) or a CPD photolyase protein (from zebrafish) in one fusion protein, with linker sequences between each component to allow the protein to fold properly. The cell penetrating peptide will allow the fusion protein to enter the cell through ionic interactions with the cell membrane [11]. Then, the NLS will guide the protein to the nucleus, which will be the main location of the DNA damage. [12]. Finally, the photolyase protein, depending on whether it is CPD photolyase or 6-4 photolyase, will repair a certain kind of DNA damage caused by UV radiation [13]. We will be using the common linker amino acid sequence GGGGS in between the three parts [14].
By combining these three components, we can create a system where the protein can be produced by bacteria and enter the cell on its own. It will then be able to repair the DNA damage caused by UV radiation itself rather than merely preventing it, as opposed to the pre existing approaches to this issue. We plan to incorporate this fusion protein in a balm or topical treatment that, in combination with preventative measures, will protect both astronauts and people on Earth from the growing problem of UV radiation.