Problem:

Melanoma is an aggressive malignancy responsible for a majority of skin cancer related deaths, in spite of representing only 5% of cutaneous malignancies. Ultraviolet radiation (UV) from sun is known to be the trigger causing damage to skin cells that eventually progress to form cancer cells. Therefore, more efficient and effective strategies to minimize ultraviolet-related damage to skin is required that affords passive and long-lasting protection. Currently, drawbacks of synthetic sunscreens are the need for applying generous amounts, inadequate coverage, more frequent applications as much as reapplying every 2 hours, ensuring proper storage, since their potency can be destroyed if stored above 77°F, and other factors that are difficult to control. Importantly, recent research has revealed that some synthetic sunscreen components can accumulate in and cause damage to sensitive aquatic environments and also cause harm to humans by acting as hormone disruptors. Therefore, one alternative to these ingredients is the biodegradable sunscreen compound Shinorine, a UV-absorbing substance produced naturally by marine bacteria. However, from the production standpoint, Shinorine, currently found in commercially available sunscreens comes from red algae gathered from the sea, but the yield can vary seasonally and geographically, thereby limiting its supply. Also, the difficulty in isolating these compounds from the cyanobacteria, such as the complex requirement of industrial level scale-up, purification, formulation, sterility, and packaging systems, can be challenging.

Our Proposed Solution:

The human skin is the largest organ in the human body and acts as the interface between the human body and the external environment. Incidentally, the only living element on the surface of the skin is the microbiome. The microbiome has an inherent ability to replenish itself, with some bacteria having doubling times as short as 20 minutes. The human skin is home to several species of commensal or nonpathogenic bacteria and among them is Staphylococcus epidermidis. Interestingly, S. epidermidis possesses genes and precursors involved in the biosynthesis of Shinorine, and therefore can be a suitable host for production of Shinorine through genetic engineering. We propose to hijacking the genes for Shinorine production from marine bacteria and inserting them into S. epidermidis so they can initiate production of Shinorine. Once we develop these nonhazardous genetically engineered strains of S. epidermidis, they can be applied on the skin surface to provide both short-term as well as long-term protection as these bacteria would serve as “living skin-protective factories” on the skin surface constantly generating Shinorine on-demand.

Innovation:

The proposed research will result in a novel, first-in-class probiotic platform for the synthesis and release of sunscreens directly on site, to prevent melanomagenesis. It will lay the foundation for a technology system that can be applied for the therapy and prevention of a multitude of dermatological disorders. To improve responsiveness to UV radiation and other environmental conditions such as heat and temperature index, we will genetically engineer the bacteria to increase production of sunscreens proportional to the intensity of UV radiation. By incorporating a sensing element, the bacteria will auto-regulate the production of sunscreens based on cues from the environment. If successful, this technology will be the first of its kind to offer sunscreen protection to skin, commensurate with intensity and level of sunlight exposure.

Impact:

While the efficacy of topically applied sunscreens diminishes over time due to unintended loss of activity and coverage, the “living factories” on the skin will form an invisible layer of sun protection on the skin surface that will achieve a sustained and extended release of “eco-friendly” sunscreen molecules. The ability of bacteria to multiply will ensure the release of sunscreens at a sustained rate in a UV light-dependent fashion and will allow for an amplified response as time progresses. This essentially means that the entire process could be completely autonomous. As a result, the beneficial effect would only increase over time without any supplemental dosage.

The skin microbiome is an underexplored niche and this project will allow us an entry into a field with limitless potential to generate genetically engineered bacteria that act as prophylactic agents, sensors, and therapeutics, to address not only environmental insults but also internal pathogenic and physiological processes.