Overview
Our iGEM project addresses the problem of inflammation in acne, which affects a wide range of population by causing physical discomfort and emotional stress/anxiety, especially in adolescents. This problem affects around 10% of the global population, and our solution offers the potential to bring about a meaningful impact through a sensor-response system.
Why This Project?
We chose this project after identifying key issues during our research phase. Specifically, we were drawn to both scientific and social challenges that remain unsolved due to the limitations of current approaches in treating skin inflammation. Our project emerged from in-depth discussions with researchers, stakeholders, and our own community and peers.
Project Goals & Objectives
Our goal will be to build an AND logic gate system that can reliably detect signs of skin inflammation. The system will work through engineered bacterial pathways where two inflammation biomarkers—nitric oxide (NO) and hydrogen peroxide (H₂O₂)—bind to specific promoters. The AND gate will only activate when both signals are present, triggering the production of indole-3-acetic acid (IAA). IAA has known anti-inflammatory properties, and its release could help reduce irritation in the skin.
To make this possible, we will design genetic circuits that combine NO- and H₂O₂-responsive promoters with downstream regulatory elements. This setup will allow us to control IAA production more precisely, keeping expression levels balanced, reducing stress on the host cell, and avoiding unnecessary "leaky" output. The design will focus on finding the right balance between sensitivity to inflammatory signals and steady IAA production.
To test our system, we will use molecular biology techniques such as transformation, cloning, and sequencing to confirm that our genetic parts are assembled correctly. For functional validation, we will measure reporter outputs to check how well the AND gate works, track IAA levels under different conditions, and verify that activation only happens when both NO and H₂O₂ are present. Together, these steps will confirm both the accuracy of our construct and its ability to function as designed.
We plan to share our data, models, software, and overall findings with the iGEM community and beyond to support collaboration and future work. This will include documenting our lab protocols, publishing experimental results, sharing our computational modeling of circuit dynamics, and providing access to the software tools we developed. By keeping our work open and accessible, we hope to make it easier for others to reproduce, build on, and improve what we started, while also contributing to the broader knowledge base in synthetic biology and inflammation research.
Inspiration & Background
Our project was inspired by challenges in skin health. Around 9.8% of the global population is affected by acne vulgaris, and teenagers are the age group that are most impacted. For many, acne and other inflammatory skin conditions cause not only physical discomfort but also mental and emotional stress through insecurity. Current treatments can be expensive, have side effects, or may be only partially effective. Seeing these gaps motivated us to think about alternative solutions.
We also examined literature and case studies on the common skin inflammation and inflammatory pathways in the body to help gain background info about our work in current science. This included reviewing research papers on inflammatory pathways and studies on the role of NO and H₂O₂ in acne. In addition, we also looked at interviews and community health discussions to better understand how these conditions impact people's daily lives, which helped us connect our project to better reflect the needs of those affected by acne around the world.
Scientific & Technical Summary
Our approach integrates biosensors and metabolic engineering to create a living system capable of responding to inflammatory signals. We plan to engineer a bacteria to perform an AND logic gate function, where the simultaneous detection of nitric oxide (NO) and hydrogen peroxide (H₂O₂), which are both biomarkers of skin inflammation, activates specific promoters. This could be done using the following methods:
- Designing and assembling genetic circuits that connect NO and H₂O₂ responsive promoters.
- Using molecular cloning, transformation, and gel electrophoresis to build and verify our constructs.
- Sequencing plasmid designs after restriction digests to confirm correct construct assembly and ensure fidelity of the engineered logic gate system.
- Incorporating computational modeling to predict circuit dynamics.
Our project diagram:
Experimental Plan
Our project follows a structured workflow:
- Design and model synthetic circuits using Benchling, Hill's Equations, and modeling of binding affinities
- Build and test constructs in E. Coli to assemble NO and H₂O₂ responsive promoters linked to IAA biosynthesis pathways
- Optimize performance and collect data based on validation of research protocols
- Evaluate real-world applicability and iterate based on feedback by developing it into topical gel formulation in the future.
Note on Scope
While our project description outlines the full design and intended implementation of our acne inflammation biosensor, our actual experimental work this year focused on cloning and sequencing validation, as well as computational modeling (Hill's Equations, molecular docking, and cell identification tools). This allowed us to test and refine the early stages of our design, while laying the groundwork for future teams to continue developing the full sensor–responder system.
References
Ji, Yun, et al. "Anti-Inflammatory and Anti-Oxidative Activity of Indole-3-Acetic Acid Involves Induction of HO-1 and Neutralization of Free Radicals in RAW264.7 Cells." International Journal of Molecular Sciences, vol. 21, no. 5, 25 Feb. 2020, pp. 1579–1579, https://doi.org/10.3390/ijms21051579.
Shaheen, Nargis, et al. "Multifaceted Role of Microbiota-Derived Indole-3-Acetic Acid in Human Diseases and Its Potential Clinical Application." The FASEB Journal, vol. 39, no. 11, 26 May 2025, https://doi.org/10.1096/fj.202500295r.
Liu, Wu, et al. "The Metabolite Indole-3-Acetic Acid of Bacteroides Ovatus Improves Atherosclerosis by Restoring the Polarisation Balance of M1/M2 Macrophages and Inhibiting Inflammation." Advanced Science, vol. 12, no. 11, 2025, https://doi.org/10.1002/advs.202413010.