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A separated sub-page on our wiki under the Team page shows the attribution clearly.

Triple negative breast cancer (TNBC) is most aggressive and associated with early metastatic recurrence. The treatment of TNBC is challenging due to limited chemotherapy responses and the absence of specific targets. The acidic tumor microenvironment caused by the high glycolytic activity of TNBC cells converts tumor associated macrophage to non-inflammatory phenotype. We are aimed to re-boost macrophage driven anti-tumor immune responses with engineered bacteria. In addition to inducing intrinsic innate and adaptative immune responses, the antitumor activities of our engineered bacteria are enhanced with five designed parts for targeting tumor CSPG4 and CD47, cleaning lactate and sensing environmental pH. Such self-propelled bacteria may be perfect robot therapies that can penetrate into tumor regions inaccessible to passive therapies. We established mathematic models, imaging techniques, portable photoacoustic device, software, and computer programs. Educational and social services were provided to raise public awareness for early detection and prevention of triple negative breast cancer. A sub-page on our wiki under the Project page shows how we initiate this project and achieve the research goal.

This is the first year of our project. We have designed five parts as our contribution. We have conducted 3 parts and one cycle of experiment including full length RNA extraction from tumor tissues, gel electrophoresis of RNA, reverse transcriptase-polymerase chain reaction (RT-PCR), generate cDNA for gene cloning and transformation in E. coli Nissle 1917. Mathematic models, imaging techniques, portable photoacoustic device, software, and computer programs were contributed. Educational and social services were provided to raise public awareness for early detection and prevention of triple negative breast cancer. You can visit our Contribution page for more detailed information.

In this first year, Guangxi-U-China team has focused on the design of parts and started one cycle of experiments. We have addressed two problems including the RNA degradation and co-culture of human cancer cells with bacteria. A mass spectrometric imaging technique was established to investigate RNases activities in normal and tumorous tissues and solve the problem. A protocol was established for the co-culture of cells. Our project contains five designed parts: targeting to tumor cells, promoting phagocytic activities of macrophages, transporting lactate, sensing acidic and basic microenvironment. In this year, we have conducted 3 parts experiments in targeting to tumor cells, promoting phagocytic activities of macrophages, sensing acidic microenvironment.

We discussed the encountered problems in brainstorming team meeting and obtained suggestions from experts. The design and performance of the project has been undergoing continuous improvement through further literature studies and Human Practices (See the Human Practices page). A lot of exciting work has been done in order to achieve the goals we set. We hope they will make some contribution to the iGEM community. For more details about our parts, you can visit our Engineering page .

We have collaborated with experts in different disciplines that help us in biology, medicine, public health, electronics, mechanics and AI. You can visit our Collaboration page and Human Practice page.

Towards our team theme “for better life and better world”, we have designed an integrated human practice. All activities in our human practices are in accordance with safety regulations, norms and ethics. We generated a report for epidemiological survey, established a public educational program, launched a public health WeChat account, designed a portable device for convenient self-checking. Those activities are responsible and good for the world. You can visit our Human Practice page for more detailed information.

In this first year, we focused on the fundamental investigations in biology as well as measurement, hardware/software, education, social services, and engineered bacteria. Social investigation and a series of educational lectures on public health or scientific lab show in the university, communities of cities and rural counties have already been implemented. A report on our epidemiological survey has been generated (see Human Practice page). The WeChat account on public health that broadcast frontiers of breast cancer research has already been open to the society from March of 2022 (see Human Practice page). Next year, the analytical techniques developed for the measurement and mathematic modeling of glucose metabolism, proteome and metabolome may be published as research articles so that they are available to the society and make some contributions to the world. About three years later, the portable device may be completed and made as a product available to those people who need it. The implementation of engineered bacteria may take very long time more than 10 years.

You can visit our Implementation page to see more details.

This year we are focusing on the integrated scientific research with social investigation, educational program, social services and the continuous improvement of the design of our project. Social investigation facilitates the identification of current social status of breast cancer occurrence, medication, disease management and policy. It is found that the treatment of breast cancer shall be very effective if early symptoms and biomarkers can be detected. Metabolic and proteomic analysis of normal and cancerous cells may reveal new biomarkers. Observation of early symptoms needs regular checking with conveniently available portable devices that should be very helpful for individual self-checking, in particular for those living in rural areas very far from cities. Educational programs are aimed to raise public awareness and provide the public with related fundamental knowledges and resources. It has also been realized that the treatment of triple negative breast cancer is very challenging because of the lack of target, low chemotherapy responses and immune escape. We decide to work on the remediation of acidic tumor microenvironments that causes the polarization of tumor associated macrophages to noninflammatory phenotype. All activities of our human practices are integrated as a whole and complemented with each other. You can visit our Human Practice page to see more details.

We have designed 4 mathematic models in this project, including a mathematic model for epidemiological survey, a model for monitoring the dynamics of glucose metabolism, a model for monitoring the dynamics of lactate production, and a model designed to perform in next year for the adaptative evolution of the metabolic network of E. coli living on lactate. You can visit our Models page to see more details.

We have proof of concept demonstration in educational program, social services, measurement, mathematic modeling, home-built photoacoustic device, software, computer programs and engineering bacteria. We have already provided a series of educational lectures on public health or scientific lab show in the university, communities of cities and rural counties. The WeChat account on public health that broadcast frontiers of breast cancer research has already been open to the society from March of 2022 (see Human Practice page for more information).

A chromatographic technique was established for the separation and quantification of glucose and lactate from complex culture medium. A mass spectrometric imaging technique was established for the visualization of changes in metabolome, proteome and enzyme activities. Changes in proteome, metabolome, the network evolvement and enzyme activities in normal and cancerous tissues are visualized with mass spectrometric imaging. With mass spectrometric imaging, biomarkers in the metastatic spread of precancerous lesions can be visualized. Please visit our Measurement and Results page for more information. Our established mathematic model has been demonstrated in epidemiological survey of breast cancer. It may be used for the monitoring of dynamic metabolism of glucose and lactate. A detailed report can be found in our Models page. A home-built photoacoustic device, software and computer programs have been established for the fundamental testing. In this year, the theoretical principle has been investigated. The home-built device was set up for the fundamental testing. One software with detailed user manual and animation show, two computer programs for fast Fourier transformation and oscilloscopic wave detection and data storage are provided on the our iGEM wiki for free download. Environmental noises can be detected with current device. About three years later, the portable device may be completed and made as a product available to those people who need it. For detailed information, please visit our Hardware and Software pages. We hope our project are helpful to other people. The construction of recombinant plasmid containing 3 designed parts has been conducted. We have conducted the extraction of full-length RNA from breast cancer tumor tissues, reverse transcriptase-polymerase chain reaction (RT-PCR), generation of cDNA for gene cloning, construction of recombinant plasmid and translation in E. coli. Nissle 1917. Their full functions will be characterized in 2023. The implementation of engineered bacteria may take very long time more than 10 years. You can visit our Project page to see more details.

We collaborate with CU-Boulder team from University of Colorado at Boulder supervised by Dr. Brian S DeDecker who works on the production of paclitaxel (Taxol) in soy plants. The research of two teams is related with the polarization of macrophages. We focus on the remediation of acidic microenvironment in which tumor-associated macrophages are converted to non-inflammatory phenotype. In contrast, paclitaxel promotes antitumor immunity through the transformation of M2-polarized macrophages to the M1-like phenotype in a TLR4-dependent manner. We and CU-Boulder team are interested in the engineering of E. coli that live on lactate and how the metabolic network of E. coli adaptively evolves on lactate. We have also discussed the collaboration on the usage of the efficient and versatile DNA assembly system called GoldenBraid to facilitate the building of genetic modules in engineering E. coli Bacteria. We have scheduled several online meetings with CU-Boulder in the design of experiments, golden gate cloning, metabolic evolution of E. coli, preparation of RNA and co-culture of human cancer cells with bacteria.Professor Corrie Detweiler of University of Colorado at Boulder provided us advices for RNA preparation.

We also have several partnerships with Professor Bifeng Yuan, Professor Ye Yuan, and Dr. Lin Zhang. You can visit our Collaboration and Partnership pages to see more details.

WIn order to improve our project, we have meet with several experts in biology, AI, electronics and pulsed laser for help. You can visit our Science Communications page to see more details.

The members of Guangxi-U-China team are majored in diverse disciplines in addition to biology. We have excellence in the areas in analytical chemistry, electronic engineering, computer science and technology, mathematic modeling and mechanistic engineering. You can visit our Measurement and Results, Models, Hardware, Software and Human practice page to see more details.