Integrated Human Practice
To get better understanding of heart failure, we visited the department of cardiology in Changhai and Changzheng hospital. By means of questionnaire and communication with the patients, we came to know that HF patients have to stay about 20 days per year in hospital to receive treatment. HF not only cost a huge amount of money but also reduced patients’ life quality. When consulting the experienced clinical doctors, the cruel truth was that no radical cure has been found for HF. The current treatments on HF are just the momentary relief for the symptoms, while the deterioration of heart is irreversible. On the other hand, the drugs costs a lot. Nowadays, the most promising way to cure HF is considered to be gene therapy. Thus, our team decided to work on gene therapy to solve this problem.
Based on these, we have consulted with our primary PI, Professor Shi Hu, who is a leading scientist in the field of Antibody Engineering. He introduced a novel nanobody termed AR185 which has been recently developed by his group and showed specifically inhibition of RyR2 phosphorylation in vitro. The nanobody, containing a camel single-domain, is known as the smallest unit that can combine target antigens. Therefore, we hypothesis that targeting RyR2 using anti-phosphorylation agents may improve treatment efficacy. We used the tech of phage display and biopanning from Frances H. Arnold, George P. Smith and Gregory P. Winter, which has just awarded the Nobel prize in Chemistry in 2018. To evaluate its potential use for the treatment of heart failure, an adeno-associated virus (AAV) based intracellular antibody delivery strategy was adopt to achieve cardiac-specific gene therapy. Then we demonstrated therapeutic effect both in cell-based assays and in vivo models. Based on the truth that circulating levels of BNP was normally very low in healthy individuals and BNP level correlated well with ventricular wall stress and severity of HF, we put BNP promotor at the upstream of AR185 gene and used ET-1 to stimulate BNP promotor through a large variety of trans.
To evaluate the feasibility of our project, we consulted professor Erwin Neher, a Nobel laureate, and Dr. Zhao Xianxian and Dr. He Zhiqing. These masters pointed out that calcium leakage was one of the most important mechanism accounted for the chronic heart failure. If our intracellular antibody performed well for the leakage, our design would obtain satisfactory improvements in treatment. While, on the other hand, they also recommended that we should explore the other mechanisms that may result into HF. Only figure out the calcium leakage problem may not be a cure for all the HF patients. To improve our project, we managed to develop our project to apply for more mechanisms after we fulfilled AR185 this year.
Do as a new iGEM team, our knowledge of iGEM competition was limited, so we searched for some instructions and suggestions about how to carry out our project. When we met obstacles and setbacks and then, we had been seeking advice from 3 teams. NUDT-China, as a team has been attending the competition for 5 times, was invited to ShangHai to introduce the iGEM process, and shared their experience in team building in detail with us. At the same time, they gave comments on our project, and put forward a lot of good ideas. For example, in our project, AAV has been used to evaluate the nanobody effectiveness. They warned us that virus should be carefully used in the experiment for consideration of biosafety. Under they help, we communicated with our hq and finally ensured the safety. During the visit to TMMU-China and Fudan-China, they showed us the details on the experiment operation and helped in avoiding unnecessary mistakes. We also attended in the 5th CCIC(Conference of China iGEMer Community)，which is one of the best communication platforms for iGEMers in China. During the conference, we learned from other teams’ experience that we enriched the form of human practice parts and tried more interesting ways to promote our projects.
After CCIC, we are inspired by other teams’ experience. And then, we decided to try some new media to promote our projects. WeChat public platforms, as a popular form of media for all-round communication and interaction of text, pictures and voice among groups, have been widely used in recent years. In order to promote our project, to let more people know about our project and to achieve the promotion of synthetic biology and iGEM project, our team established our own Wechat public platform, the Internet Work Number. Whenever our team has a influential social practice, we will send a WeChat push to record the moment. For example, the summer camp, attending CCIC, you can find the details in our WeChat public platform. As a new media, Shakes is appealing to the youth for the characteristics of short, fast and trendy. Our team used Shakes to record the details of our experiment, both happy and sad memories. Through this comedy form, we can record the problems we encountered in the operation of the experiment. In this way, we can not only spread the idea of joyful experiment, but also record our team's best memory of youth. Himalaya FM, as the initiator of audiobooks, has great influence in China. We rely on this platform to introduce synthetic biology to our readers on the basis of the book Synthetic Biology and Applications written by Dr. Markus Schmidt. Through all the new mediums we talk above, we are able to achieve a more diversified level of promotion work, which is an important reason for our use of these. By popularizing synthetic biology in a way popular with the mediums, we can achieve the final goal of human practice: to let more people understand synthetic biology, and really let synthetic biology come into the general public. In return, some audience commended our efforts on these media. We felt encouraged by these comments and all our efforts seemed to be recognized by the public. Although this process is fulfilled with obstacles and setbacks, we even wanted to give up for several times. As long as what we do is helpful for the welfare of human beings, we will devote all we have to this career.
To memorize our project, we designed our team logo and project logo. Also, we designed a moral for our project. We gave lectures to high students from 12 provinces/cities and 13 middle schools across the country participating in the summer camp. We introduced our projects to these high school students and recommended them to engage in the high school competition. We volunteered to Yanji geracomium to contribute our love for the traditional Mid-Autumn Festival. We gave a voluntary physical examination and gave speech on the prevention of HF. The elderly there were satisfied about our job. We helped to solve their confusion on how to exercise and go on a healthy diet. Through this trip, we recognize that prevention is much more important than treatment. Only stay a healthy lifestyle, can we lower the risk of HF.
