- Proof of Concept
- Dry Lab
- Wet Lab
- Integrated Human Practice
- Meet the Team!
Helicobacter pylori (H. pylori) is the only known pathogen that can settle in the stomach for a long time. It is one of the main culprits of gastritis, peptic ulcer, gastric lymphoma and other gastric malignant tumors. At the same time, this kind of dangerous pathogenic bacteria is also highly infectious, which can cause family aggregation infection by sharing tableware and food together.
The defects of existing treatment strategies are in a dilemma. The lack of drugs is mainly reflected in the resistance of H. pylori to triple therapy. The Meta analysis of China in 2017 showed that the average success rate of triple therapy was reduced to 71.1%, far below the acceptable rate of 80%. H. pylori also maintains a very rapid evolution rate, even after thorough cure, it has a recurrence rate of more than 3% and ber drug resistance. In addition, the side effects of antibiotics and antacids used in triple therapy and quadruple therapy are serious, and long-term medication has great damage to human liver and kidney.
Besides, the co-evolution history of H. pylori and human beings is as long as 60,000 years, so the relationship between H. pylori and us is not a simple parasitic relationship, but symbiosis. According to the review of Blaser, the eradication of H. pylori has significantly increased the incidence rate of esophageal cancer and gastric acid regurgitation. Therefore, in the treatment of related diseases caused by H. pylori, the best strategy should be to control the number of it in a reasonable range.
On the asteroid B612, the little prince, who was tired of pulling up the baobab seedlings, got a sheep, which would chew off the sprouts on the ground in time, thus forming a ternary equilibrium ecosystem (or system) with the little prince and the baobabs. So for the treatment of H. pylori related diseases, we can also design a "SHEEP", so that it can eliminate the extra H. pylori at any time, and maintain the homeostasis of gastric micro-environment.
The full name of our “SHEEP” is Stomach Homeostasis Establishment for Eluding the Plethora of H. pylori. The therapy consists of three parts: the engineered bacteria that can produce drugs and target to kill H. pylori; an electronic capsule that can move freely in the stomach to take samples and photos to obtain the information of H. pylori infection; and a model that can simulate the balance process of engineering bacteria, pathogens and immune system, and predict for individualizing the treatment plan according to the infection situation
Figure 1: Gene of LL-37 under the anaerobic induced promoter, PfnrS
Lactobacillus acidophilus is a common bacteria that can colonize in the stomach, and has already been used to treat gastrointestinal flora disorders. In addition, as probiotics, it can also effectively inhibit H. pylori.Our project chose Lactobacillus acidophilus as classic organism and constructed three modules in it to target and kill H. pylori: drug production module, ammonia sensor and biosafety module controlled by cold-induction on-switch.
LL-37 is a human cathelicidin with a good killing effect on H. pylori and can be expressed in prokaryotic cells. we put its gene under an anaerobic induced promoter so that we can primarily lower the off-target effect.
Fig.2 Engineering bacteria track Helicobacter pylori by monitoring ammonia concentrations in the environment
The function of ammonia sensor is to target H. pylori which can decompose urea into ammonia to neutralize gastric acid. When the engineering bacteria sense the increase of ammonia concentration, the activity of glnAp2 will be inhibited, then lysis protein after the inhibitory transcription factor (TetR-tetR/tetA promoters) can be expressed , so as to release drugs to kill H. pylori.
We designed a capsule device for detecting engineered bacteria and verfied some modules design. It consists of a microcamera, float part of magnetic levitation system, sampling device and am external magnetic field control system. Microcamera connected with external device, which works in the dark, enables us take real-time images of stomach. Magnetic levitation system can locate precisely the capusule in the place we want, such as the lesion. Then sampling device can take gastric sample s and store it inside, waiting for analysis. Currently capsule robot can hardly complete the same work in stomach. Our design meets our needs and fills this vacancy. We expect to expand its functions further in the future.
So far, no parts have been uploaded.
To transform our DeCaffi program into a successful product facing caffeine beverages consumers, our Human Practices focus on creating a close loop between raw material processor, product producer and consumer group.
Raw Material Processor:
We visited coffee shop chains and independent cafes, learning the future trends of coffee industry, exploring possibilities to broaden the application scenario of a caffeine degradation product. “Nowadays, what is on the shelves should not be products, let alone technologies, but culture.” Inspired by a store manager, we are devoting to creating a coffee culture where people can carefully manage the caffeine intake.
We are keeping on communicating with food enzymes preparation manufacturers and coffee cup producers, making sure that our product can fit into the caffeine beverages industry chain safely and favorably.
Questionnaires were used to collect the opinions of caffeine beverages consumer groups, from which we determined that the core of our product design should be portability and efficiency. (We plan to introduce caffeine, theacrine, enzyme preparation and transgenic products to the public through WeChat small program.)
Beyond the program, we are ambitious to launch an iGEM online education platform, where teams can share training materials, seek cooperation, exchange experiences and make friends. We are looking forward to a future where it would be easier for fresh men to walk into the door of synthetic biology and enjoy the fun of iGME.