Team:BNU-China/Human Practices

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First of all, we evaluated the possible impact of our work in practical production by visiting one of the most notable synthetic biology companies in china, Bluepha. According to their suggestions, we accomplished our project design. We then visited three experts, respectively majoring in biochemistry, microbiology and phycology, creating an interdisciplinary communication environment. Based on their feedback, we successfully designed a series of educational lectures about synthetic biology for high school students. Furthermore, we successfully collaborated with OUC, UCAS, UESTC and took an active part the CCiC conference. To intuitively demonstrate the core idea of synthetic biology and inspire people to participate in gene-designing process, we deigned the first electronic-display system of synthetic biology, e-SAM©, and we hope this device can facilitate future iGEM teams to promote their ideas to public.

The problem of degradation always lies in industrial production, whereas the abuse of antibiotics has lead to the emerge of antibiotic-resistant superbugs. It's the researchers' responsibility to deal with this safety issues raised by the interaction between the application and the human society. Our iGEM project aims at the application of self-screening advantageous mutant selection, which can provide a growth dominance to the strains with beneficial mutation. As a result, we conducted an biosafety-investigation about the medical application of antibiotics in FuXing Hospital, Capital University. Besides, we participated in a series of academic conferences, during which we exchanged our ideas with other participants and sought out for chances of collaboration.

Prof. Dr. Zhuxudong

Editor of Chinese Journal of Biotechnology

Mycological society of china

Beijing normal university

It is a real pleasure for us to have prof. Zhu as our mentor. Pro. zhu has been instructing igem teams for over 5 years and he provided extremely helpful advice not only on how to build up a wonderful igem team, but also on how to design a feasible experiment plan and how to carry it on safely. Moreover, he introduced us to several scientific authorities.

Pro. Zhu made us fully conscious of the oncoming challenges in igem competition, for example, he emphasized the importance of maintaining a harmony relationship between teammates, which could directly decide the final results to some degree. As a result, we made great efforts to assure everyone at the proper position, which finally helped us to accomplish our project in turn.

Prof. Ye Huan

Chief physician, department of infectious diseases, Fuxing Hospital

At the beginning, we focused on no-antibiotic screening in recombinant strains. To figure out the current use of antibiotics in medical and laboratory research, we talked to Dr. Ye from Capital Medical University. He indicated that the ability of screening specific strains without antibiotics would undoubtedly be a great breakthrough in fundamental research. However, he also pointed out that the use of antibiotics is irreplaceable in medical healing but dosage and extensive application are strictly stated in our law. Dr. Ye made us aware of the fact that the abuse of antibiotics is in fact a very severe problem afflicting modern society.In parts, this problem is, as Dr. Ye says, the strict controls of top laboratories making the leakage of superbugs hardly possible. Dr. Ye thus recommended a close collaboration with industrial companies for the law forbids the use of antibiotics in mass-producing fermentation. After the discussion, we continually focused on overuse of antibiotics and drafted a manifesto calling for the legislation of biosafty with the help of ZJUT.

When it comes to industrial biology, we came up with the idea of providing growth advantage, leading to the final selectivity of recombinant strains and useful mutants. Dr. Ye was fascinated by our ideas and claimed that applications of self-screening system will have a high demand for usage in the industrial business.

Prof. Xin Mingxiu

Chinese society of microbiology

Beijing normal university

As our project is mainly about the self-control of microorganisms, we thought it is necessary to consult prof. Xin for some advice. Having been engaging in industrial organism for decades,Prof. Xin is one of the most qualified experts in fermentation industry. Prof. Xin greatly appreciated the prospect of our parts’ application in industry, but he also mentioned that the ethical, social, legal, and environmental impact of a concept usually unfolds when it is transformed from a novel idea into reality ,especially when it is applied to the practice of production. Compared to the professional technicians, we lacked necessary industrial experience, so we surveyed LooKChem®, a leading biotechnology company in Hunan, China.

We focused on two questions during the investigation:

How does a biotechnology factory control the stability of strains in huge-amount gross production?

When our idea of automatic selection is converted into an application, what should be thoroughly considered?

LooKChem®

About these questions, Dr. Peng gave us two important information. The first is when it comes to the biological legalization, an automatic cell factory is forbidden to use antibiotics which is usual in laboratory work. As a result, they have to concentrate and separate the solution in order to sustain the recombination strains account for the majority of total strains. This is the central concern of our project. He also pointed out that the most common degradation happens when plasmids unequally distribute in cell cycles to let normal bacteria with less burden replace the recombination strains and resulting in the declination of total production.

In order to assure the practicalities of our SAM project, we've contacted a lot of experts, companies in related fields to acquire information on the prospects, potentials and weakness of this technique. Throughout these interviews and investigation, we've developed a profound understanding on the interaction between our project and the society, which in turn has enlightened the further study.

Prof. Yang Dong

Chinese society of biochemistry and molecular biology

Beijing normal university

After reading numerous papers,we came up with the first idea of self-control system consisting of a series of genes collaboration, and discussed with prof. Yang. In spite of her appreciation of the sophisticate network we designed, she regretfully denied its feasibility. Prof. Yang pointed out that a truly valuable plan for practical use must be concise because when we introduce heterologous genes, we add to more variables at the same time, which will greatly increase the probability of our potential failure.

But during the discussion, we came to an agreement that fermentation incubator could be considered as a natural field of natural selectivity. In this theory, the core reason of strain degradation is the strain without recombination plasmids or the mutated strains could get rid of the burden of heterologous protein while maintaining the same ability to absorb nutrition and growth. As a result, the recombination strains were gradually eliminated in this competition.

This discussion lighted our another inspiration. Since the recombination strains can get growth advantage by losing heterologous genes, maybe it is possible for us to make recombination strains’ growth velocity overcome the normal, and reach the target of maintaining genes by converting the evolution direction.

After consulting to the papers, we decided to use TGATG linkage between two genes as our final project.

Bluepha

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Dr. Li Teng, CEO

Dr. Li suggested two potential areas about the application of our project. The first is an automatic cell factory that can select beneficial mutations. He also suggested engineering regulatory parts to make the self-screening system capable of applying to different substrate and desired products.

We discussed with chief information official Dr. Li model analyzing. He suggested that we can competition model for prediction of sequence candidate performance during screening. The talk inspired us a lot for how to convert our project into an application, especially in modeling and designing.

Biological safety is one of the major issues of consideration since the very beginning of our project. But in practice, fuzzy expression is inevitable in legal language. Therefore, we established a collaborating program with ZJUT to produce a manifesto, calling for laws to regulate the use of antibiotics and biotechnology.

Prof. Ma Jianyin

National Academy of Foreign Legal History Study

The editor of China Nonprofit Review

We contacted the experienced judges Prof. Ma to get legal opinions on our research project. They were not able to give us a legal assessment, because the state of medical controlling in China based on too many different fields of law to find a quick answer. Instead, Prof. Ma explained to us his personal opinion. From his point of view, as long as it was safe and good to humanity, scientific research should be as unrestricted as possible. However, the abuse of antibiotics has lead to a series of environmental and medical problems including decreased immunity and antibiotics-resistant superbugs. The fundamental cause is the misunderstanding of biosafty. As a result, scientists should take the responsibility of popularizing scientific principles and promoting the legislation about life science. In addition, with the help of social media, researchers can lead discussions, clarify research topics, and help to determine moral values. Prof. Ma set a high value on our manifesto calling for laws to regulate the use of antibiotics and biotechnology and encouraged us to doing research for improving the general life quality of mankind.

click here to get the full text of legislation manifesto

During the summer vacation, our team members went to country schools in Ningxia and Jiangxi Province to promote the popular science of synthetic biology. Furthermore we successfully designed a series of educational lectures and open-laboratory-festival for high school students. As a team rooted in solidarity, we successfully collaborated with OUC, UCAS, UESTC, HBUT, ZJUT, HUST and took an active part the CCiC conference. Most importantly, we were the first iGEM team applying logical circuit to human practice. In order to intuitively demonstrate the core idea of synthetic biology and inspire people to participate in gene-designing process, we deigned e-SAM©, the first electronic-display system of synthetic biology based on SCM parts, and we drafted a detailed description of experiments that can be performed with it as well as suggestions for customers. We are convinced that e-SAM© system can greatly facilitate future iGEM teams to promote their ideas to public.

Introductory courses

Since we came from a special college for teachers, we wanted our goals for the event to inspire more people to get involved in science. The head of the program emphasized that we should try to get students interested in the field of molecular biology and participating in research in college. Every summer, Beijing normal university hosts an education campaign for bachelors of all major to learn iGEM and do basic biological experiments, in order to arise their curiosity of synthetic biology and life science. The BNU-China iGEM teams always collaborate with the School of Education in the past to do teaching activities with students, so we launched a series of introductory course for new students, and invited them to visit our lab.

The courses include 4-week training of basic theory, two molecular biology experiments, and a mini-iGEM meeting. To guarantee the quality of these courses, we chose four of our best teammates and rehearsed privately for several times. Moreover, we made thorough plans and got the full rights from both college leaders and former iGEMers, each of whom assigned a team of freshers matched according to students’ speciality. The mentors monitored the study pace of each student by weekly meetings and students responded to learn the required materials. The courses were liked by most of apprentices. More importantly, we had a real bonus that we met two excellent students with both talent and enthusiasm, and they were absorbed in our iGEM team to make greater contribution.

Voluntary

Frankly speaking, popular science about biology is quite inadequate, causing many students in rural areas unable to scratch the surface of biology until senior high. As a result, during the summer vacation, our team members went to three country schools in Jiangxi and Ningxia Province for volunteer work and brought biology to younger students.

BNU-China organized a seminar class and shared anecdotes about biotechnology with children from several villages. In the active class, team members held a heated discussion involving transgenosis and environmental protection that people concerned and we got established a long-term friendly relation of cooperation with OUC-China, who helped us with the comic book about synthetic biology. The book exhibited the complex biology model and principle with funny comics, making it more easier for students initial contact. Besides daily activities, we also conducted an interview about their fancy ways of education. Most students responded that they were looking forward to participating in scientific experiments, but had laboured under the disadvantage of not having enough equipment. Their words went directly to the heart, finding their support in the understanding. Grown up in cities, we had no idea of strong thirst for knowledge of rural children. From then on, we were deeply determined to create a revolutionary new way of science popularization, ameliorating the poor condition and offering these lovely students opportunities to a better future.

e-SAM

Having been back to our laboratory, we held a series of conferences, coming up with ideas on how to popularize synthetic biology intended for demonstrations at low cost.At the beginning, we planned to help students to get a deeper understanding of synthetic biology in the means of lecture, but soon changed our mind for the teaching practice with local high school students who reported that this form would be boring for the public. Then we thought of, a mimic electrocircuitt relying on the gene pathway would offer a great advantage of viewable and intuitive understanding of the core idea of synthetic biology. And it can inspire people to participate in gene-designing process.

As a result, we used e-SAM© system, an ideal analog model to expound the definition of synthetic biology, applying engineering structures to build artificial biological systems for research, engineering and medical applications. We also drafted a detailed description of experiments that can be performed with e-SAM© system as well as suggestions for customers. The one-to-one match between e-SAM© system and the biology parts are shown below.

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Fig.1

Based on this year’s igem project, self-screening for advantageous mutants, we designed the first electronic model for synthetic biology.

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Fig.2 Basic design of SAM model

In our parts, target genes interposed in MCS can co-express the following growth factor via the TGATG linkage. This logical circuit is devised to represent the control relationship between genes.

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Fig.3 A circuit diagram for e-SAM© system

Then, we opened a DIY class for high school students and successfully mocked up the first type of e-SAM model.

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Fig.4 e-SAM© physical model

With the help of e-SAM system, we can demonstrate gene-expression with modifying the switches.

Visit and feedback from high school teachers

In September, the team welcomed students from several high schools nearby and freshers in BNU, who had interests in biology and the willing to introduce our model to their friends. A few days later we received encouraging students’ responses from SanFan and other departments of BNU, who gave a high appraisal to our engineering model and told us to provide them with a more detailed proposal as soon as we would have it ready.

As a result, in October, several high school teachers from SanFan came to BNU to meet with our team to discuss the possible integration of our e-SAM system in their high school's biology curriculum. We provided them a live demonstration of how the e-SAM system works and we discussed the impact it would have on the high school courses of normal students heatedly. The teachers responded to us that one of the most disturbing questions about science curriculum was the lack of facilities. Many essential science instruments such as centrifuge can be too dangerous and too expensive for high school provide. They e-SAM system can make great contribution at teaching-cost reduction, worthy to spread across high school education.

Click here to get the detailed e-SAM protocol