Team:ShanghaiTech China/Demonstrate
This time we are focusing on diabetes, which affects a large population all over the world. Typically, people suffering from type 2 diabetes need regular oral antidiabetic drugs taking or traditional insulin injections. Although these treatments effectively bring patients’ condition under control in most cases, it is still inconvenient and complex to use, especially for its storage and carrying.
Therefore, we came up with an idea that people can use some intelligent devices to automatically adjust the insulin level. This could allow the diabetics get rid of cumbersome insulin injection. In addition, through the optimization of intelligent control algorithm, we can adjust the insulin level to better suit patients’ conditions.
However, to accomplish this idea could be tough work.
Fortunately, we found NAS to make all of this come true. NAS is the abbreviation of N-acyl synthase which can simply use glycerol and hexadecanoic acid to produce palmityl serinol. And palmityl serinol, a member of N-acyl amide family, has been proved to be a ligand of the G-protein coupled receptors (GPCRs) and have an excellent effect on stimulating the body to secrete insulin. Added with a pDawn light control part and nanoparticles, the system can run pretty well under the continuously changing light source regulated by the intelligent control device. In addition, we explored the agarose vesicle as a carrier to deliver our engineered bacteria into the intestine.
1. Wetlab
*We’ve tested the expression level of NAS under the induction of IPTG in the E. coli. And we verified the correct expression of our target product by mass spectrum.
Details: https://2019.igem.org/Team:ShanghaiTech_China/NAS
*We’ve constructed the pDawn-mEGFP plasmid. And the correlation curve between protein expression and culture time in several different culture conditions.
Details: https://2019.igem.org/Team:ShanghaiTech_China/LightControl#3-characterization-of-pdawn-system
*We’ve constructed the pDawn-NAS plasmid. And we verified the correct expression of our target protein.
*We’ve added a nanoparticles part so that we can change the 980nm near-infrared(NIR) to 440-483nm in the user’s body. So that we can use red light as given stimuli, which will reduce possible side effects of direct usage of blue light.
Details:https://2019.igem.org/Team:ShanghaiTech_China/Nanoparticles
*We’ve explored the use of agarose vesicle which can protect the engineered bacteria from extreme pH suppress. Also, the vesicle can limit the growing scope of the bacteria to just near the vesicle so that the lifespan can be prolonged.
Details:https://2019.igem.org/Team:ShanghaiTech_China/DrugDelivery
*We’ve added a killing switch to the whole system to make sure the engineering bacteria cannot escape from their working environment. By using the lysis enzyme, the bacteria will suicide under the induction of changing temperature or specific chemicals.
Details: https://2019.igem.org/Team:ShanghaiTech_China/Safety
*We’ve also improved the whole system by changing the promoter and photosensitive part of the pDawn element. So that we successfully mitigated the downside of leaking.
Details:https://2019.igem.org/Team:ShanghaiTech_China/LightControl#4-characterization-of-modified-pdawn-system
https://2019.igem.org/Team:ShanghaiTech_China/Improvement
2. Hardware
Based on Bluetooth technology, we’ve established a set of “INSULEN Waistband”. Made up by three parts: the waring part, the signal receptor and the light emitter, this belt can receive the real-time changing signal from user’s smartphone and give photo-stimuli to the engineering bacteria colonized in user’s intestine. In our in vitro experiments, we used blue light as the given stimuli to the bacteria because of the better availability of pDawn part. But according to our deeper investigation, we changed to use near-infrared light as stimuli for its better penetrability and fewer side effects.
Details: https://2019.igem.org/Team:ShanghaiTech_China/Hardware
3. Software
One of the most important parts of our system is the software. Based on the Android platform, we built an app to receive and process the blood sugar data. It has an algorithm to calculate the user’s preference of mealtime and automatically regulate the frequency and intensity of the stimulus. This app is also an image generation software. Users can clearly get the changing curve of their blood sugar levels. Around these basic content, more useful functions are coming soon. We want to build a platform to promote the information exchange between the diabetics and the medical professionals. We can even build a community for diabetics to help each other. Maybe we can also link this app with our games about synthetic biology to make science popularization more interesting and vivid.
Details: https://2019.igem.org/Team:ShanghaiTech_China/Hardware#insulen-app
4. Model
Our model is of great help to the following aspects of INSULEN:
*Predict the proliferation of engineered E. coli in INSULEN.
*Predict the competitive proliferation of engineered E. coli and the original E. coli.
*Estimate the expression of effective substances using E. coli growth.
*Estimate how effective substance expression affects blood sugar.
*Using the model to solve the problem that INSULEN is not convenient for real-time monitoring after it is actually applied to the intestine.
Details: https://2019.igem.org/Team:ShanghaiTech_China/Model
5. Human Practices
*We’ve made a computer game called “Cell War”, to make it easier for people to feel the beauty and magic of synthetic biology. An open-source game map building platform is built into the game, in which the players can let their creativity flourish and communicate with other players.
Details: https://2019.igem.org/Team:ShanghaiTech_China/Public_Engagement#game-design
*We are also very enthusiastic about public education activity. We organized many educational activities and delivered several lectures to from primary school students to undergraduates to let more and more people have a deeper knowledge about synthetic biology and reduce their misunderstandings.
Details: https://2019.igem.org/Team:ShanghaiTech_China/Public_Engagement#education
*To make the education process livelier and more interesting, we made a cartoon video and uploaded it to the bilibili (a video website).
Details: https://2019.igem.org/Team:ShanghaiTech_China/Public_Engagement#video
*We did an investigation through the Internet to see how the public respond to our idea of bacteriotherapy.
Details: https://2019.igem.org/Team:ShanghaiTech_China/Human_Practices#questionnaire
*We also visited some domestic professor in this area, asking for their advice and analyzation on the implantability. Then, according to their suggestions, we updated some parts of our project.
*We invited several volunteers to try the INSULEN waist pack on and made some significant improvements.
Details: https://2019.igem.org/Team:ShanghaiTech_China/Human_Practices#user-experience
Concept
With the achievement of all parts above, the whole system can run as an automatic blood glucose regulation system. First, the monitor detects the signal of elevated blood glucose level and delivers the signal to the INSULEN application of the user’s smart device. Then the ‘INSULEN Waist Pack’ will be instructed, through Bluetooth, to emit a certain amount of near-infrared. The 980nm near-infrared will be transferred into 440-483nm blue light, which is the effective input signal of pDawn, by nanoparticles part. After the stimuli of 440-483nm light, the pDawn-NAS bacteria will start to secret N-palmitoyl serinol in the intestine. This molecule, a ligand of the human GPCRs, can stimulate the promotion of insulin secretion and the blood glucose level will drop down to the normal condition.