Team:NEU China A/Human Practices

As Peter Carr said,” Human Practices is the study of how your work affects the world, and how the world affects your work”, HP is the link between our experiments and real life and is an integral part of the project. Therefore, we need to carefully design our HP to promote our work to real life, and improve our project to benefit the world based on feedback from HP.

This is NEU_China's third trip to iGEM, and the members of team A are mostly major in biomedical. We are quite concerned about the advances in biotechnology and the cutting-edge research that can make a difference in the medical field. So we want to try a new track, Therapeutics.
Once in a group discussion, a team member shared that her sister's experience with inflammatory bowel disease (IBD) and we became interested in it. After reading some academic literature, we found that the incidence of IBD is related to the destruction of intestinal bacterial strings, and the incidence of this disease in China is increasing. Therefore, we chose the treatment of IBD as the topic of our project. In addition, we refer to past projects and hope to control the disease by a release of immunosuppressants by engineering bacteria.

1 Questionnaire

The literature shows that IBD is frequent in young, so we want to investigate young people's understanding of gut health and IBD. We produced relevant questionnaires and posted them on a social website, and ended up with 291 responses.

After the survey data came out, we immediately analyzed and discussed with our instructor, professor Ding Chen. Here are some important conclusions:
i. Young people know less about bowel disease and IBD
Only a few people pay attention to information related to intestinal diseases, and most people only pay attention to information related to problems or other special situations. Awareness of intestinal diseases and IBD is low in some developed regions.

ii. Young people have a concentrated source of information about disease

When we surveyed participants for information on bowel disease or health, we found that the vast majority of their information came from the Internet.

iii. Young people lack intestinal health awareness
When asked if they would take care of their gut health in their daily lives, nearly 80 percent of the participants said they would not take care of their gut health. This contrasts sharply with the rapidly rising incidence of the disease.

iv. Intestinal diseases affect people's normal lives

For participants who have been identified with bowel diseases, we asked questions about the impact of bowel disease on their lives, most of whom believed that it affected their lives. Some even thought that some bowel diseases significantly reduced their quality of life.

v. In the treatment plan, people care most about efficacy

In this questionnaire, we asked participants what factors they were most concerned about in the treatment regimen. Participants were asked to rank the effects, costs, side effects, risks, and access approaches, and most of them rated efficacy as most important, followed by cost, side effects, risks, and ease of access. This inspires us, when designing treatment, in order to satisfy people's expectation to cure, work hard on curative effect more.

vi. Most people do not know about bacterial therapy

Finally, we asked the participants to talk about their acceptance of our proposed treatment. Those who fully accept and reject are in the minority, and most people hold a neutral attitude.

Conclusion

This questionnaire has timely solved some problems of our team and pointed out the direction of our future work.
Ⅰ. Public understanding for the intestinal disease and IBD is insufficient, we need to do some of the other more popular science activities to publicize the relevant information, improve the awareness of the public.
Ⅱ. The selection of drugs and treatment design needs to consider a number of factors, we should collect more social opinions, trying to make an effective, safe and easy way of treatment for those people in need.

2 Promotion

After completing the investigation and the design of the preliminary scheme, we want to make some changes in the current situation of low recognition of inflammatory bowel disease among the youth groups. So we delivered a presentation about IBD, synthetic biology, iGEM competitions as well as our programs into more people's lives. To the end, we made a three - fold booklet and poster. We not only distribute our reading materials in public places such as communities and libraries near the campus but also put our reading materials on the reading shelves in the hospital halls and beside the school medical room, hoping that more people can learn about IBD and synthetic biology.

Nearly 100 brochures were distributed to introduce the use of synthetic biology to treat IBD. Many people were impressed by our original intentions and behaviors, and expressed their support and admiration for us. Some even expressed their sympathy for patients with inflammatory bowel disease.

3 High School Lecture

On July 26th, we came to the Northeast Yucai High School in Liaoning Province to give a speech to the third-grade students who are about to enter the university. We detailed the iGEM competition, knowledge about synthetic biology and our projects. Many high school students were interested in biology. They asked questions actively and enthusiastically, and we had conducted more in-depth exchanges. We also taught high school students to do a DNA gel electrophoresis with the plasmids constructed in our project. The basic operation of molecular biology experiment has aroused everyone's strong interest in biological experiments.

4 Visitation of Patients

We went to the inpatient department of Shengjing hospital affiliated to China Medical University to interview a patient with ulcerative colitis(UC) to learn more about IBD.

The 64-year-old patient was diagnosed with ulcerative colitis in 2016. This is the second time she has been hospitalized for severe illness when we came to her. Through the visit, we learned that:
Ⅰ. Ulcerative colitis seriously affected her life. She had chronic abdominal pain and diarrhea, poor energy, and inconvenient use of the toilet. When coming on, defecate is accompanied with hematic frequently, a dietary difficulty made her complement nutrition with fluid food only. She is depressed all day long.
Ⅱ. The illness comes up repeatedly and the treatment cycle is long as well as expensive. Because it's a lifelong illness and you need to take a pill every day after being hospitalized. Better drugs like biologics are expensive, even up to about 10,000 USD a month. Less effective drugs are not covered by Medicare. Coupled with the repeated illness needs to be looked after by the family and society has brought a burden. The financial and mental burden of an inflammatory bowel disease patient is enormous.
Later, doctors also told us that there has always been a large number of patients who have got inflammatory bowel disease, while more than 20 IBD patients in a floor of this inpatient department. Crohn's disease primarily affects young people while ulcerative colitis occurs at all ages. Patients are more likely to choose medication and few will undergo surgery.
The interview exposed problems with existing treatments, such as the difficulty of effectively curing IBD for long. The rapid spread of inflammatory bowel disease is taking a huge toll on individuals, families and society. It also presents huge health risks, as more and more people are getting sick and the situation will only get worse if they are not dealt with in time. Patients and society are looking forward to the emergence of a new type of treatment. Our team should not blindly pursue curative effect when designing the scheme, but also consider the economic benefits and accompanying risks.

5 Vegetable Planting

In addition to IBD patients, we want everyone to have a healthier gut. So we're going to grow broccoli this fall. Thanks to the efforts of our team members, we successfully cooperated with the university to open up a small field of broccoli on the unbuilt campus wasteland.

Broccoli is not only our source of sulforaphane, but also an accepted healthy dish.We plan to distribute our broccoli to IBD patients, campuses and surrounding communities, hoping that people will pay attention to gut health and develop healthier eating habits.
Thanks for everyone’s time and support. We believe that more and more people will pay more attention to their intestinal health in the future and give more care and understanding to IBD patients, be interested in synthetic biology, and be willing to contribute to the cause of human health.

1 Expert Consultations

After completing our survey of youth groups, we consulted professor Sheng finished his Ph.D. degree at the University of Illinois at Chicago and a post-doctoral degree at Harvard Medical School. He is now a professor at theInstitute of Biotechnology, School of life science and health in Northeastern University. He is majoring in Wnt signaling pathway. Sheng was 2016 overseas tutor of NEU-CHINA team. Besides, he is an expert on colorectal cancer and has some knowledge of most bowel diseases.

He made the following Suggestions for our project design:
Ⅰ. Looking for the right chassis, E. coli Nissle can be used as chassis
Ⅱ. Select the nitric oxide as inflammatory bowel disease of nonspecific inflammation signal molecules
III. Sustained and stable output is required for anti-inflammatory devices.

2. Doctor Consultations

After choosing interleukin-10 as the output of engineering bacteria and conducting experiments for a period of time, in order to find out the feasibility of our scheme, we went to consult with professor Zheng Changqing, a first-line expert in intestinal diseases. He is the director of the department of internal medicine of Shengjing hospital affiliated to China Medical University and the director of the second department of gastroenterology.

Dr. Zheng Changqing introduced the treatment of IBD from the aspects of patients' disease, current clinical treatment methods, and common drugs.
Ⅰ. Doctors say using bacteria to secrete TNF an immune inhibitor is an effective way.
Ⅱ. Compared to mammalian cells, bacteria are more easy to operate and mass culture. They have more potential. However, the issue of safety should be carefully considered and bioprotective measures should be taken to avoid biological leakage.
III. Common anti-inflammatory drugs are commonly used in patients with mild to moderate symptoms, and immunosuppressive agents are more commonly used in patients with Crohn's disease.
Ⅳ. We know that IBD and diet and the changes of intestinal bacteria strains. During the communication, we also learned that the prevalence of IBD in China has skyrocketed in recent years, and currently the number of effective drugs is limited. Expensive biologics are not covered, and patients rely on ordinary anti-inflammatory drugs. It will be very meaningful if our therapy can be applied effectively in clinical practice. Inspired by professor Zheng, in the future, we will combine engineered bacteria to release immunosuppressive and TNF monoclonal antibodies.

3 Mobile Games

Based on our treatment plan for inflammatory bowel disease, our team designed a simple game. In the game, players play engineered bacteria that travel through the fire-filled gut, collecting nitric oxide emitted by inflammation and releasing the drug interleukin 10 to destroy the flame to help the gut recover. The upper right dial shows the health of the gut, the left is healthy and the right is critically ill. In difficult circumstances, our E. coli needs to fight not only IBD but also colorectal cancer. Fighting, warriors!

4 The 5th CCiC

On August 27, we attended the fifth CCiC held by ShanghaiTech university.

We presented our project at this meeting and had communication with other iGEM teams.

While communicating with the SJTU-BioX-shanghai team, we learned about another pathway of perceived nitric oxide-mediated by the promoter PyeaR. We wanted to compare the performance differences between the promoter PyeaR they used and the promoter PnorV we used later. In addition, an iGEMer introduced the improved SYNB1618 strain obtained by E. Coli Nissle 1917 with better safety. We are prepared to use this strain in the future. Through this meeting, we made a lot of friends and got a lot of useful advice.

5 Visitation of Pharmaceutical Factory

We wanted to make the lab work available to the market one day, so we asked ourselves if there was a possibility of mass production of the drug in our program. It is what we need to think about. With such an issue in mind, we visited pharmaceutical companies.

While some of our outreach to our community was short-term, we worked closely with our community partners to ensure that our impact does not end with this project. We will construct an organization aiming to learn more about IBD and other intestinal disease,and to devoted ourselves into the cause of provoking people's awareness of these diseases.

During the whole process, the researchers introduced to us the production method of the drug Zhengchangsheng, which inspired us to make our engineered bacteria into capsules for oral use by patients in the future.

Team:NEU China A/Human Practices

Human Practices

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