In the course of our project research, we primarily focused on three areas of analysis: "Targeting Module Optimization," "Gene Selection and Analysis," and "Safety Assessment." These components worked closely together, providing strong support for the project design. Modeling and experimentation complemented each other: experiments not only raised questions and requirements for modeling but also provided key data for the construction and refinement of the models. At the same time, through optimizing experimental conditions, predicting outcomes, completing visualizations, and validating hypotheses, modeling significantly enhanced the efficiency and accuracy of the experiments. This close interaction systematized and refined the research progress, fostering more innovative breakthroughs.

In the Targeting module, structure simulation, molecular docking, and molecular dynamics simulation were employed to enhance Salmonella's targeting ability. Through pan-cancer analysis, integrins were found to be highly expressed in various tumors, leading to the selection of RGD peptides as the targeting unit. Multiple RGD variants were analyzed for affinity differences with integrins. Using AlphaFold3, a fusion protein structure containing RGD, iRGD, and RGDFK was constructed and optimized. Molecular docking and dynamics simulations analysis confirmed that Lpp'-OmpA-RGD exhibited the most stable binding with integrin, making it the final choice for the targeting unit. This to some extent helped us avoid unnecessary work while linking wet experiments with dry experiments.

In the Gene Selection module, we selected 14 different types of tumors. For each tumor type, we conducted analyses and identified candidate genes suitable for RNAi. Specifically, we first obtained a large amount of transcriptome data from the tumors and then performed differential expression analysis. Next, we conducted gene enrichment analysis to understand the associated pathways, giving us an initial understanding of the gene functions involved. Finally, we performed prognostic analysis and identified potential RNAi targets. Additionally, during the webpage design process, we intentionally formatted this section as a dictionary, making it convenient for iGEMers to use and expand upon in the future.

In the Safety module, we initially employed mathematical modeling, including ordinary and partial differential equations (ODEs and PDEs), to explore immune system dynamics after Salmonella injection, focusing on macrophage-cytokine interactions. By integrating experimental data, we simulated bacterial diffusion, macrophage activation, and cytokine regulation, identifying key parameters through sensitivity analysis. We then simplified the PLGA nanoparticle model and applied six mathematical frameworks to investigate drug release mechanisms, such as diffusion, erosion, and swelling, using model fitting and prediction to optimize the drug delivery system. Finally, we developed an ODE-based model to quantify Salmonella growth dynamics and delayed lysis within host cells, revealing that delayed lysis significantly impacts infection dynamics, supporting its potential to enhance safety.

In the entire model, the significance lies not only in completing a specific project analysis, but more importantly, in the development of a dry-lab analysis method applicable to "engineered bacteria." By modularizing bacterial functions into a "Targeting Module," "Functional Module," and "Safety Module," we were able to perform more personalized and modular analyses. Along with the project's completion, we retained many elements with potential for development and sharing, such as the dictionary-like design in the Gene Selection module. For more information, view our Model.

On the Integrated Human Practices page, we vividly showcase how we establish a feedback loop between content design and stakeholder expectations. Our iHP initiative is of an unprecedented magnitude, and we are committed to ensuring that our work is not only scientifically solid but also ethically proper and socially responsible. On the iHP page, you will sequentially encounter a visual overview of Project Planning & Experimentation, Entrepreneurship, and Bioethics. You can thoroughly explore the specific activities and feedback through the respective filters. First, the overall design and operations guarantee the scientific validity and feasibility of the project through meticulous planning and execution, thereby ensuring high-quality research. Second, the entrepreneurial process accentuates how to transform laboratory results into practical applications, thus driving socioeconomic development. Finally, ethical inquiry guides the team in considering social responsibility and potential risks during project implementation, ensuring that technological advancements contribute to human well-being. Through an in-depth examination of these three dimensions, we aim to achieve harmonious development between technology and society, ultimately striking a balance between innovation and responsibility.

Three thematic axes link all our efforts in human practice, ensuring that BIOTARGET has a responsible impact on all relevant fields and groups, encompassing science, safety, ethics, legal regulations, and business. Ultimately, this explains how our project will gradually achieve real-world applications while continuously learning and refining itself throughout the process. For more information, view our Human Practices.

Our educational progress is underpinned by our core educational philosophy: "To strive, to seek, to find." We have integrated this philosophy into every step of our educational initiatives. Guided by this core philosophy, we organized 22 creative and in-depth activities, expanding from traditional classrooms to interactive summer camps, interpreting natural sciences through the art lens, and transforming real-life challenges into professional reflections. Our approach to education goes beyond the traditional “I teach, you learn” model. The events adhere to a cyclical approach: brainstorming, implementation, feedback, and reflection, forming an iterative loop that enhances each subsequent initiative. The activities covered a wide range of age groups, from schoolchildren to the elderly. We broadened our horizons as our educational efforts reached over 10 regions worldwide. In total, these 22 activities benefited more than 10,000 people from diverse social backgrounds. Throughout the process, JLU-NBBMS established close connections with 15 colleges and 30 iGEM teams. We reached diverse audiences, from primary school students to the general public, teaching biology, synthetic biology, bioart, biosafety, and disease treatment. We believe in the power of education to inspire future generations. Through our initiatives, we hope to support and guide future iGEM teams. Our mission is not only to make scientific progress but also to spark curiosity and innovation in the global community. To see more, view our Education.

We achieved engineering success by four engineering design cycles, including “Target module”, “Safety module”, “Gene regulation module” and “Drug delivery module”. Through engineering, we finally optimized the design and validation pipeline of Bio-TARGET system, and succeeded in completing the functional validation and efficacy validation. To see more, view our Engineering & Result.

We continually engage with the global community and gather extensive feedback from diverse international and national sources to direct the broad scope, objectives, design, and laboratory experiments of our HP project. For details, view our Human Practices.

Competition Deliverables

We have and will fully complete the required deliverables.

Wiki (finished)

Promotion Video (finished)

Presentation Video (finished)

Judging Form (finished)

Judging Session (will fully complete it)

Project Attributions

We have clearly attributed all the work completed by the team members and external help in Attributions Page using Attribution Form. To see more, view our Attributions.

Project Description

Chemotherapeutic drug resistance is a major challenge in cancer treatment. Therefore, we focused on creating Bacterial lterative Optimized Therapy and Assisted Resistance Guard Enhancement Technology, Bio-TARGET. To see more, view our Description.

Contribution

In terms of model, we have used a range of bioinformatic methods to enhance the accurate identification of security and targeting in Bio-TARGET system, which can be used for similar iGEM projects. In terms of experiment, each module construction and combination in Bio-TARGET system can be used by other iGEM teams. In terms of HP & Education, we published our ideas in detail for other iGEM teams to read. To see more, view our Contribution.