Human Practice
As a medico, clinical internship is essential in our career. When we started our internship for the first year, we found the truth was much crueler than we imagined. We thought that as long as we followed the treatment and medication according to the textbook, we can greatly relieve patients’ suffering, and, to some points, we may even cure their diseases. However, on the contrary, during the internship in cardiology department, there were too many patients cannot get cured for heart disease because there was no medicine can stop the process of heart failure. The current treatments on HF are just the momentary relief for the symptoms, while the deterioration of heart is irreversible. We can do nothing but watch the patients’ condition get deteriorating, and eventually evolve into heart failure. To get better understanding of heart failure, we did a research in the department of cardiology in Changhai hospital. We designed a questionnaire to investigate the basic information and severity of disease. The patients were admitted in our investigation according to the inclusion criteria:
(1) Diagnosed as heart failure in accordance with criteria from the Chinese Medical Association Cardiovascular Society's "Guidelines for the Diagnosis and Treatment of Chronic Heart Failure";
(2) Over 18 years old;
(3) Informed consent and signed informed consent.
The patients were excluded according to exclusive criteria:
(1) Mental illness or cognitive impairment;
(2) Complicated with severe organ dysfunction or malignant tumor.
The content was designed according to the NYHA classes for heart failure. Some patients’ relatives answered the questionnaire because these patients were unable to fill in the questionnaire. The research was conducted from March 1st to September 31th in the cardiovascular department of Changhai Hospital. There were totally 76 patients admitted into the test. And we can find that the average cost on the HF treatment is about 47.32 thousand yuan per year. The average hospitalization time is about 18.78 days per year.
By means of the research, we found out that HF not only poses a great threat to the physical and mental health of patients; on the other hand, patients' families also suffer tremendous economic pressure. Seeing these sad facts, we can't stop wondering if we can find a treatment to HF .
Based on that, we 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 is normally very low in healthy individuals and BNP level correlates 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 some masters in this filed. We listened a lecture on cell therapy given by Prof. Erwin Neher, a Nobel laureate. Prof. Erwin Neher specializes in cellular ion channel function, whose work helps in explaining the mechanism of heart disease. After the lecture, we presented our project to him. He speaks highly on our project and 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, he also recommended that we should explore the other mechanisms that may result into HF.
We also consulted Dr. Zhao Xianxian, Dr. Liu Yang, Dr. Wang Zhinong and Dr. He Zhiqing. They are experienced clinical doctors in thoracic surgery and cardiology from Changhai and Changzheng hospital. They pointed out that the main clinical treatment for heart failure is medication currently. And the most important drug is the so-called Golden Triangle, which consist in ACEi/ARB, βRB, diuretic. After decades of clinical practice, medications have been matured. However, these drugs can only delay the symptoms and do not improve or prolong the patient's survival time. Therefore, the prospect of gene therapy is broad. 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, we need 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, Fudan-China and TMMU-China. 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 meeting, we listened to a few lectures given by Guoping Zhao, academician of CAS, and many other masters in synthetic biology. The different views of the masters on synthetic biology inspired us to look into the problem we met in our research in another way. As a preview, three of our team members gave a presentation of our project in English and answered questions from judges and other iGEMers attending to the meeting. During the process, we found many drawbacks of our program, such as the bio-safety parts and modeling parts. We were suggested again to hand over the safety form to the organizing committee of iGEM due to the use of virus. We were also recommended to build a mathematical modeling, which should be closely attached to our research to guide the production and ensure the effects of the antibodies. These parts were not considered in our project because we were unfamiliar with the rules and the competition. But, luckily, these problems were pointed out by the judges and iGEMers. In the poster presentation, our team visited many outstanding teams’ posters to learn about their experiment design and other good points in human practice, mathematical modeling and so on. Near the end of CCIC, we joined in the round table conference with Meagan Lizarazo, Executive Vice President and Chief Operating Officer of the iGEM Foundation. In the conference, Mrs. Meagan shared us experience on the Giant Jamboree, like how to deliver a good speech, attentions on the trip to America and so on. Through CCIC, we learned more about iGEM not only in the attentions and points, but also attracted by the positive research atmosphere. Everyone in the iGEM team had tried their best to fight for more and more achievements and came up with new and better ways to fix the teams’ trouble.
After CCIC, we were 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, synthetic biology and iGEM, our team established our own Wechat public platform, the Internet Work Number. Whenever our team has an influential social practice, we will send a WeChat push to record the moment. For example, the summer camp, attending CCIC, you can find all 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.
Team logo
The spinning DNA double helix wraps around the name of our team, symbolizing the technology of synthetic biology as the cornerstone of all our future projects. Two gears in the upper right are the finishing touches, representing the important inspiration of engineering biology in our projects. The overall open composition implies the open and innovative thinking of our team.
Project logo
In 2018, our team's project logo consists of Oracle's heart in Chinese, shield, branch and DNA double helix. The overall shape of the figure looks like a shield, also like the "heart" in the oracle bone inscriptions, indicating that the purpose of our project is to protect the heart. The trunk of a branch is made up of double helixes of DNA, symbolizing that the cornerstone of our technology is synthetic biology. The leaves are the symbol of vitality, showing that after the treatment of our medicine, the heart is rejuvenated.
Moral
The core of our project is to antagonize the phosphorylation of s2808 site on the calcium channel RyR2, the key site of heart failure, through the protection of AR-185 antibody, so as to avoid calcium overload and ultimately inhibit the deterioration of heart failure. We think of AR-185 as a warrior who protects the S2808 locus of cardiomyocytes. They're targeted and powerful. The s2808 locus is a home that they need to defend.
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.
