Team:NJU-China/Human Practices

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Overview

Our team has been focused on targeted gene expression in certain cells for a long time. While this year, we had a thought of whether the delivered genes’ localization occurred in different areas in cells themselves? We hope to provide new strategies to cure relevant diseases in this way. With such a question, we first learned about neuronal diseases caused by abnormal neurons as a special kind of polar cells. Next, during the talk with neurologist, specialists and other iGEM teams, we knew that it was possible to provide a new strategy to cure some diseases in this way and asked them for some details about the subject and experiments. The practices were closely integrated with our project as we improved our experiment design according to different experts and stakeholders’ opinions. Besides, we went to Nanjing Foreign Language School in Chinese Brain Health Month to hold a communicating lecture to inspire high school students’ interests of curing diseases using targeted protein expression with improved elements, synthetic biology and iGEM.

Integrated Human Practices

In this part, we discussed our goal, design and execution with as many experts and stakeholders of the general public as possible, so that we could get their opinions and ask for their advice in order to shape our design and improve the experiments as best possible.

Interview with Doctors

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At the very beginning, we came to Nanjing Brain Hospital and had an interview with a rehabilitation teacher and a head-nurse there. Where we went was children’s intensive care ward in Brain Hospital. In a colourful and warm environment there, medical staff introduced the present situation of brain hospital and neuronal diseases. As the earliest national neurology hospital, it has more than 800 thousand outpatient visits and 18 thousand inpatients per year. There was one case of ‘Fragile X Syndrome’ in their hospital, a kind of neurological disease with high incidence in North America, characterized by erroneous localization of mRNA and proteins in neurons. In such case, we started with this disease and tried to construct new combined targeting elements effective for the mis-localization.

Visit to OBiO

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Since our team planned to use exosomes as molecular carriers, we would like to know how it is in neurons. Then we went to OBiO Shanghai, a high-tech enterprise integrating basic research service, gene therapy drug research and development and clinical recombinant virus industrialization preparation. In the visit to OBiO Shanghai, we discussed with specialist Dr. Diao the safety and rationality of the design and execution of our project. While, during the discussion, we were more clear about the advantages and possible disadvantages of the usage of exosomes and AAV as molecular carriers and realized that our original plan remained some defects indeed. Dr. Diao generally approved our design but pointed out the possible defects at the same time. She believed that when it comes to vessels with the ability of targeted transporting molecular substance, AAV virus are more efficient than exosomes. Our old friend, the exosomes, are good molecular carriers in that they are natural and highly compatible to the cell. But the expert pointed out that further consideration of the transportation efficiency of exosomes and the duration of the effect should be carried out in our experiments. The content inside the exosomes, are not universal, so the future of exosomes as drugs is probably not that bright. However, Dr. Diao encouraged us to conduct the experiments synchronously both with AAV and exosomes to compare the effect by ourselves. Also, she suggested that systematic injection would be preferable to targeted injection.

What she pointed out gave our experimental design a valuable and precious improvement. In fact, during our later experiment, it comes out that the efficiency of exosomes encapsulating mRNA is very low.

What’s more, Dr Diao told us, virus has been coming into sight as an important carrier in gene therapy. For example, lentivirus can be used in CAR-T due to its ability of gene integration. However, in the cure of genopathy, the AAV virus is a better choice in that it can cause slight immune reaction in the body and the effect can be rather prolonged. Because the virus genome will not be integrated with that of the host cell, the safety of application of the AAV can be guaranteed. Moreover, AAV has the capacity of passing through the blood brain block and this enables us to use AAV for transportation of target elements to work in the neurons. While, our original carrier, exosomes, cannot transport contents universally like AAV.

In addition, with the interaction with biological company, we learned about the current situation in the policy and industry of viruses or exosomes in medicine. As to the policy aspect, we learned that in order to boost the development of new therapy, the government policies regarding the examination and approval of viruses as drugs is rather slack now. But some detailed tests as the intracellular remain of viral DNA or proteins or the endotoxin should be carried out strictly. Still, with the irreplaceable advantages, the viruses are still our top choice in gene therapy. To our relief, with the development of technology, the cost of developing is lower than before, which means that it is a better era of gene therapy. After the visit, we were convinced that what we were doing was greatly potential and good for the world.

CCiC

Conference of China iGEMer Community is a national iGEM communication summit hosted by Chinese universities. It was founded with the aim of idea-sharing, communication and cooperation among iGEM teams, and promoting high-level discussion of advanced issues pertaining to the promotion of international Biosynthesis issues. CCiC schedule simulates that of iGEM Giant Jamboree, with each undergraduate team presenting their project and display posters, seeking out to be an academic conversation and experience sharing conference, while providing an interactive platform for training teams at the same time.

In September this year, we participated in the annual CCiC summit held in ShanghaiTech University. There, we met more than 60 teams from all over China. While displaying our poster, we had close talks with numerous teams, introducing the project design and progress, and shared our achievements and puzzles when working on the project. From the discussion, we took their advice and learned from their experience to improve our project. For instance, there was a team producing their experiments without adequate control groups, decreasing the accuracy of the experiment and even bringing a failure of the project. So, we checked our project again and won the Best Presentation Award in the end.

Besides, we attended a communication meeting with iGEM teams in Nanjing held at Nanjing University. During this exchange, we communicated with Pro. Haoqian Zhang and shared experimental stories with several teams. By listening to diverse novel ideas, we marveled at all of the brilliant thoughts and were constantly developing our own project ideas.

Education & Public Engagement

In this part, we organized a special lecture for the high school students in Nanjing Foreign Language School on International Alzheimer’s Day with NFLS iGEM team, which included introduction of IGEM, Synthetic biology, our project and experiments in a plain and vivid way. We also organized simulating experience for Alzheimer's disease and autism, which highly improve the public understanding about brain disease and the possibilities of synthetic biology and appeal more love and care to patients of neuronal diseases.

In the special lecture for high school students, we used logical relationship of simple experimental parts to show them what synthetic biology and iGEM competition is and how we perform our subject. When introducing, we focused on the tortuous process of our project design and the improvement according to the result of every attempt. We discussed with high school students how to make an affective element for certain purpose. The conversation discussed the possible treatment for brain disease with synthetic biology and also sparked students’ scientific curiosity.

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In the next part, several students volunteered to experience simulating experiments held to enable them feel the difficulties caused by neurological diseases about our subject. We provided VR glasses for them and they could use these special glasses to watch certain special videos which recorded visual world of patients with autism or Alzheimer’s disease. For example, a girl student saw what a little boy with autism saw with VR glasses. The boy in the screen was sitting in a mall with his mum, while the girl student said she felt uncomfortable and helpless throughout the whole process. “I’m trying to imitate others and spare no effort to contact with the outside, but nobody understands me.” Because the boy with autism could feel every subtle change of light and sound and enlarge them, he was easy to become anxious and restless. Worse, people with autism couldn’t communicate with others so that nobody could relieve them, in which case, they were caught in a vicious circle.

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Here are some feedbacks from students in NFLS:

i) Xth: This activity opened a window of synthetic biology for me, bringing the advanced technology close to our everyday life: experiments in the lab can actually make a difference to cancer patients, children with inabilities and even to ourselves. The lecturers from both team NFLS and NJU spoke in a very simple but professional way. More importantly, their collaboration made the introduction comprehensive and diversified.

ii) Szh: Though tough to learn, biology, as a branch of science, explains many natural laws, which help us get a clearer and more comprehensive understanding of the world. Some biological knowledge can be applied to our daily life and brings to us more convenience. During this workshop, the speakers explained to us profound theories concerning biology in simple terms, while the experience of VR enabled us to get access to the mental world of autistic children. It is really a fantastic meeting, together with the rich offering of a delicious snack.

iii)Yax: Honestly speaking, I am not the kind of girl who is very into biology. The complicated structures and processes drove me mad from time to time. This activity, however, won the interest of mine. Unlike the traditional classes, the speakers made good use of technology while successfully getting close to our daily lives. This made all the process not hard to understand. I’d say that everything was pretty interesting when you viewed the world in a positive way. I got the precious chance of experiencing the life of children with autism under virtual reality. Every scene was so real - the desire to be noticed, fear, loneliness, loss, sadness, loneliness and Great Depression filled my mind and heart. Heart broke into pieces on the floor. I would never expect the kids to suffer from all this. Crowded parties, happy people talking with smiles on their faces, bottles striking hard, food emitting smell, and ME-in the corner of the room, alone, crying in my heart. I was so down that I was about to shout out to the people nearby, I wanted to, but I couldn’t.” That’s hopeless, but, maybe I should hopeless.

We NJU-China believe that it is possible to put forward a new method to cure more diseases with synthetic biology. Thus, through human practice, we aim to let high school students learn more about neuronal diseases and our subject and also encourage them to participate in the study of biology, especially synthetic biology and have a closer contact with iGEM. Meanwhile, we also had access to improve our project through their precious feedback in return.