Team:NEFU China/Human Practices

loading...

Top

Home

Team

• Members
• Attribution
• Collaborations
• Gallery

Project

• Description
• Design
• Graphic Design

Parts

• Basic
• Composite
• Improvement

Results

Lab

• Experiments
• Protocol
• Notebook
• Safety

Model

HP

• Overview
• Education & Engagement
• Community

Judging

Human Practice

GOLD MEDAL CRITERIA

By communicating with Professor Shulin Liu, our bacterium engineered to express CD convert the nontoxic nucleoside analog with antifungal activities 5-FC into a highly cytotoxic chemical, 5-fluorouracil (5-FU), which can suppress the bacteria in the healthy tissues. Besides, Dr. Wang suggested that we can learn more about drugs doses related to killing tumors to further optimize our treatment. Through communication with experts in the biopharmaceutical factory, we learned that if our system can be used in the production, we must concern about safety problems, how to avoid the contamination of miscellaneous bacteria and how to ensure the purity of the engineered produced bacteria.

SLIVER MEDAL CRITERIA

In our case, we used engineered bacteria, an effective tumor therapeutic to kill tumor cells. We also took the public response to our case into account, so we conducted a questionnaire survey on the public. What’s more, we took measures to let the public really accept our case and let more people know synthetic biology, so, we carried out popular science activities, and used Wechat, a smartphone app, to push our article in public.

Overview

Impact

Impact

Surgery, radiotherapy, chemotherapy and molecularly targeted drugs are the major approaches of treating cancers nowadays. Among them, the first three represent the most common treatment strategies. However, we cannot deny the problems existing in these traditional treatment methods. As for the side effects of the surgery, it is difficult to completely remove cancerous tissues or cells to achieve radical cure of cancers. On the contrary, there is high recurrence rate because of the metastasis of cancer cells. Furthermore, in terms of radiotherapy and chemotherapy, not only the intolerable processes and harmful side effects on normal cells frequently happen, but also rapid and massive dissolution of the cancer cells sometimes cannot be effectively avoided, which may lead to various complications, such as acute hyperuricemia and nephropathy. For therapies using molecularly targeted drug, there are problem in agent acquisition and low target efficiency, as well as substantial cost. At the same time, cancer cells have to be emphatically noted in their mutations and issues of drug resistance.

×

Strategies

Strategies

Based on the facts described above, an effective tumor therapeutic approach with reduced risk of acute uric acid nephropathy is urgently needed. With the rapid development of synthetic biology, bacterium-based cancer treatment has become an emerging way of cancer therapies with a great potential of clinical applications due to its reinvention and sustainability. Therefore, we decided to use engineered bacteria to release anticancer agents and simultaneously prevent accumulation of uric acid as a result of rapid and massive dissolution of the cancer cells. It will lead to cancer cell killing and prevention of nephropathy. In our system, with the engineered bacteria systematically delivered into the body, the bacteria in normal tissues will be eliminated in response to 5-Flucytosine (5-FC), while the majority of the bacteria will be attracted to the tumor sites to exert their anticancer activity. In this system, whether the engineered bacteria kill tumor cells depends on uric acid levels. When uric acid level at tumor sites is low, bacteria will release the anti-tumor agent. However, when uric acid reaches a certain level, the bacteria will slow down the release of the anti-tumor agent and express uricase to reduce uric acid levels. Therefore, we will accomplish the goal of killing tumors and at the same time avoiding the occurrence of acute uric acid nephropathy, which will let us treat cancer patients gently and safely.

×

Goals

Goals

To popularize bacterium-based cancer therapy and synthetic biology, we designed a questionnaire and found the promotion method of publicity that people could easily accept. The public thought that there are problems in immunoreaction due to the infusion of bacteria into human blood vessels. Then, we went to a high school to propagandize synthetic biology and published essays on the Internet for its popularization.Overall, we made effective improvements to our project based on the results of our series of actions.

×

Education & Engagement

Questionnaire

Science presentation

Social Media

Purpose

In the early stage of our project design, we conducted a questionnaire survey in order to further investigate the current widespread problems in cancer treatment, objectively evaluate and optimize the project design, and lay a foundation for the follow-up Human Practice work.

Popular questionnaire

We have published a questionnaire on the Microsoft platform in both Chinese and English, and actively spread it through WeChat, QQ, Twitter, etc. Up to now, over 650 questionnaires have been completed.

Survey Design

According to different aspects in this questionnaire, we proposed 17 questions in order to understand the views of different populations between new biological approaches of cancer therapies and traditional cancer treatments. We wanted to know whether people from different populations could accept the concept of using bacteria to treat cancers and what they might concern about. We also wanted to know about the current problems in cancer treatments, what the public focused on in order to optimize our project. In addition, we wanted to investigate the extent of general public's understanding of synthetic biology and the treatment of cancers using bacteria. According to the feedback from the general public, we aimed to take appropriate measures to carry out the follow-up publicity and popularization of the project.

Result collection and analysis

We surveyed people of all ages from industries and most of them had at least bachelor degrees. we investigated public awareness and attitudes about current cancer treatments.

According to the survey results, the general public is relatively familiar with traditional treatment methods, but not familiar with the emerging biological therapies. Moreover, they are concerned about a series of problems existing in traditional treatment strategies, such as long and painful treatment process, high treatment cost, large side effects and possible recurrence, etc. Therefore, our program should work towards simplifying the treatment process, reducing the pain and side effects, and ensuring the long-term effectiveness of the treatments.

In our design, modified bacteria would enter the body through intravenous injection, colonize in the microenvironment of tumor cells, release anticancer agents, and finally kill tumor cells. Compared with the traditional methods, bacteria with strong tumor-targeting specificity require relatively low medication dosage, Consequently, toxicity and side effects on normal tissues should be minor, and bacteria can automatically control the release of the anticancer agent without human intervention, which simplified the therapeutic procedure. Simultaneously, our therapeutic method can theoretically keep a relatively long period of validity after a single injection, and the degree of pain during the treatment is greatly reduced. In addition, the cost of this treatment strategy is relatively low. These advantages enable our project to specifically address a series of problems existing in the traditional cancer treatment methods. Therefore, we finally determined the implementation of the project of bacteria treatment for cancers.

Besides, according to the survey, most people knew little about synthetic biology and just heard about it. Thus, if we want to further propagandize our project and collect suggestions, it is very important to popularize the basic knowledge of synthetic biology. According to the investigation, people tend to acquire knowledge through the ways of popular science lectures and network media.

Therefore, we added more detailed introduction on web design projects. We used popular science lectures and preaches to promote our project, popularize the knowledge of synthetic biology and collect the feedback.

In addition to these questions, we also surveyed the public on the treatment of cancers via engineered bacteria. Most people did not know about bacteria cancer therapy, but they believed that modified bacteria could be used to treat cancers and thus showed expectation to this approach, which gave us confidence to move forward with our project. The concerns of many people about this treatment plan focused on the safety assurance of bacteria to human body. Therefore, we decided to first conduct publicity lectures on our project to let the public know more about the detailed method of bacteria cancer therapy. In addition, we decided to strengthen a safety module for our engineered bacteria.

Purpose

According to our survey results, the public tends to acquire scientific knowledge through seminars. So, in order to further popularize synthetic biology knowledge and let more people understand our project, we carried out popular science activities.

Location

We chose Harbin No. 6 High School as the venue for our first presentation.

Preliminary preparation

We personally designed the poster and a lovely lab experience invitation.

Main speaker

Teacher : Pengchao Wang Undergraduate: Yaru Gu

Introduce

First, we used a simple example of why cows eat grass and produce milk, and brought students into the world of synthetic biology step by step, letting them understand that the bulls graze but do not produce milk because of lack of milk production genes. If we can use synthetic biology to introduce their milk-producing genes, it is possible to make bulls produce milk. Next, we used LEGO bricks as an example to let the students understand the practice of synthetic biology. We put forward the concept of “Telling knowledge, Building and Using”, and playing a fun and easy-to-understand biological video to stimulate students to build their interests to biology.

Question & Discussion

We promoted the students to discuss based on what they were watching, and provided the students with the opportunity to visit our lab.

Teacher Wang: If you could bring five things to Mars to survive, what would you choose?

Wang Zihan: All the genes of the organism, all the crop seeds, water, human germlines and nutrient solution.

Teacher Wang: Actually, there is no clear answer to this question, but as long as you bring the DNA synthesizer and the chassis microbe, it is enough to meet the requirements of genetic diversity.

Project Introduction

Later, in the form of comics, we vividly introduced our entries to the students and asked many questions about biology. The students had a heated discussion and answered our questions. Among them, Li Molin, without any knowledge of nuclear function, perfectly replied that "the nucleus is the gene pool and metabolic control center." These answers were very thoughtful. We were very much inspired, and felt the interest and yearning of the students to synthetic biology.

Fun experiment

In order to let the students further feel the charm of synthetic biology, we brought the bacteria that produced the rose oil through our transformation, and showed the students a very visual X-gal experiment.

End

After the main content of the presentation was completed, the students were still actively asking us different knowledge about biology and expressed great interest in synthetic biology. Finally, we expressed sincere gratitude to the students and teachers who watched our presentation, and took a group photo. So far, the Harbin No. 6 High School Seminar was successfully concluded.

Social Media

Another approach to engage with the public and let more people understand synthetic biology was to use WeChat, a smartphone app, to publicly push our article. Reaching out to the public domain via social media platforms was an essential part in our project. In today's fast-paced era, online reading is a convenient and fast way to understand new knowledge. Reading on the network is an effective way of engaging people and spread the concept of synthetic biology. We regularly pushed science knowledge about biology. From students of primary schools to the elderly, people of different ages paid much attention to our articles. Our regular posting included details and the progress of our project. The public can participate in the project in time to truly understand the real parts of the experiments. This will better attract the public to understand and accept the knowledge of synthetic biology. The social media were successfully employed in engaging the public to complete surveys, as well as serving as a vital tool for communication and collaboration between different iGEM teams. We concentrated on promoting our team as being approachable and open to collaboration with the public and other research groups.

Community

Dr. Shulin Liu is the Dean of the School of Pharmacy, Harbin Medical University, Director of the Genomic Center, Professor and Ph.D. tutor.

According to the high targeting of Salmonella, focus on constructing the gene cassettes to improve the targeting effect of E. coli nissle 1917.

Dr. Liu gave us guidance about the bacterium-based treatment of cancers, highlighting the fact that cancers are heterogeneous. His insights made us consider the targeting of bacteria in the body, and prompt us to learn other effective methods of bacterium-based targeting. He explained to us the targeting of Salmonella. Dr. Liu recommended reading about certain research studies, and this enabled us to find evidence to prove our case.

Inspired by the discussions, we improved our case by overexpressing cytosine deaminase in engineered bacteria in normal tissues. The premise is that low toxicity 5-Fluorocytosine (5-FC) to bacteria can be transformed into 5-Fluorouracil (5-FU) with obvious bacteriostatic effect, which was proved to increase the safety and tumor-specific targeting.

College of Wildlife Resources Management, Northeast Forestry University.

We made an important improvement on the safety of using bacteria in mammals, and reduced the total amount of engineered bacteria through the designed pathway.

Dr. Wang is specializing in animal physiology. We discussed with him to gain knowledge of physiological immune response. He provided us with invaluable insights regarding drug dosage standard. He encouraged us to research the approaches being accepted in clinical settings, and advised us on future experiments, in which we could collect experimental data to reflect the efficacy of this treatment and conduct further cellular experiments.

We revised our experimental design based on his suggestion and reduced the total amount of engineered bacteria through adding design of cassettes. We visited a biopharmaceutical company to learn a series of issues related to production and safety.