Overview
Figure 1: XJTLU-CHINA 2019 Team HP Design
Figure 1 showed the main concept of this year's HP work. To better conduct our project, we reckoned our project as a product. Therefore, our main goal was completing the product design, which contains discovery, development, reflection, and expectation. Also, we referred the prospect of the product as an important part of our design. Since our product was a therapeutic product that might be released into the market, we paid more attention to the safety and ethical issue. The duty of HP work was pushing product design forward step by step. Inevitably, the engagement with public would be involved.
Figure 2: XJTLU-CHINA 2019 Team HP flowchart
Figure 2 briefly showed the Human Practices work we've done this year, which was written in chronological order.
If you're interested, please scroll down for more information. The side navigation bar can take you to where you'd like to go faster.
Discovery
XJTLU iDreamer —A Competition Simulating iGEM on campus
After team building, we planned and held a simulated mini iGEM competition in XJTLU.
Why did we hold this activity?
At the beginning of team building, we hoped to get more ideas for project establishment. Therefore, we held a college-scale activity -- XJTLU iDreamer. In addition, we also hoped that students in XJTLU could have a deeper understanding on what research is and learn to discover and explore the world better.
How did we implement this activity?
We held an opening ceremony and arranged a round table discussion on five exemplary study topics. Participants were free to form teams and submit application forms for their projects. In the winter vacation, each group carried out their own projects and present their results in four different ways: Report, Poster, Video and Presentation.
What did we learn from this activity?
Hundreds of people took part in the event, including eight teams shortlisted in the final round. The research direction of these eight teams were different from each other, covering a broad range of fields, including atmospheric pollution, pet diseases, drone, depression disease, and so on. We had in-depth communication with all the teams, and after considering the practicality issues and difficulty levels of the projects, we decided to focus our running project on “Disease Treatment”. In addition, through this activity, we realized that our team could promote the iGEM club in the campus and promote our activity via WeChat public account, so as to expand the influence of iGEM on campus and attract more students to learn about synthetic biology and modern science.
Communicating with professors
Prof. Minyan Wang
Why did we communicate with Professor Minyan Wang?
Professor Minyan Wang is an Associate Professor in XJTLU's Department of Biological Sciences, whose main research direction focuses on neurological disorders in the nervous system. After holding XJTLU iDreamer, our team considered to continue to complete the project of 2018 XJTLU-CHINA. Last year's project was to treat neurodegenerative diseases with drug via using exosomes. Therefore, we decided to communicate with Prof. Wang first, hoping to get some guidance.
What did we learn from the communication?
Prof. Wang affirmed our project idea and suggested that we can study the use of the protein EAAT2. She said, the etiology of neurodegenerative diseases, its is numerous, and is still hard to conclude. As a team of students, we may start with the effect of EAAT2 on glutamate uptake, which is a channel protein. We may try to reduce the glutamatelevel to relieve the symptoms.
Prof. Dechang Xu
Why did we communicate with Professor Dechang Xu?
Prof. Xu is the director of the Research Office of XJTLU and one of the PIs of the iGEM XJTLU-CHINA team. He has assisted the iGEM team in biological modeling for many years and is also familiar with synthetic biology. For more project guidance this year, we asked Prof. Xu for help.
What did we learn from the communication?
After learning that we were considering using exosome as a delivery tool, Prof. Xu suggested that we can establish a regulation model of the three-plasmid system for better research about how to promote and improve effective exosome production in the drug production stage. In addition, Prof. Xu recommended us Matlab, python and other software for biological modeling.
Professor David Sung Kay Chiu
Why did we communicate with Professor David Sung Kay Chiu?
Prof. Chiu is an Associate Professor in XJTLU's Department of Biological Sciences and one of PIs of the iGEM XJTLU-CHINA team. We are inexperienced in safety training so we turned to Professor Chiu for help and guidance.
What did we learn from the communication?
Prof. Chiu assisted us in the lab safety, and guided the design and conduction of our experiments so as to avoid serious technical problems during the experiments.
Brainstorming
Why did we brainstorm?
Brainstorming is an activity that helps the team focus on creating new ideas. After completing the basic laboratory safety training, consulting large amounts of relevant literature and discussing with relevant professors, we had to choose the direction of our project and push it forward. Therefore, we decided to hold a brainstorming session to focus on the team's ideas and determine the final direction.
How did we conduct this activity?
In the early stage of this brainstorming, our team members divided themselves into groups to search literature in different directions, including the functions of exosomes and EAAT2 protein. Meanwhile, members of the modeling group studied and tried using Matlab and other softwares.
What did we obtain from the brainstorm meetings?
During the brainstorming, our team members actively put forward their own ideas and generated several new ideas in the discussion. Finally, based on the estimation of experimental materials and difficulties, we chose to study EAAT2 protein and make it one of our core parts in treating the disease. At the same time, our modeling section will adopt Prof. Xu's suggestion to study the Three Plasmid System as a guide for the future project development.
The iGEM Shanghai Conference
On 13th of April 2019, we were invited to attend the iGEM Shanghai Conference held by the NYU Shanghai iGEM team.
Why did we attend this meetup?
After the brainstorm meeting, our project topic was basically finalized. But we still had many uncertain questions related to the iGEM competition. After knowing that NYU Shanghai would like to have a meetup, we participated in it with passion. We hoped to communicate with more iGEMers, exchange experience with each other and learn from each other through this meetup.
What did we learn from the meetup?
As requested by the organizer, we presented our 2018 project on the conference and got to know numerous friends from other teams. Most importantly, we got acquainted with the iGEM Asia Ambassador Dorothy Zhang. Throughout the entire iGEM year, we have maintained a long-term and constant communication with Dorothy, which helps us have a clearer understanding of the iGEM competition and the judging criteria. With her help, our project moved towards the correct direction.
Development
2019 Seminar on Exosomes and Diseases
From April 19th to April 20th, six of our team members went to Shanghai to attend Seminar on Exosomes and Diseases held by Bioon, which is a new biomedical media portal of MedSci. Bioon is committed to sharing very fresh life science research information and biomedical industry trends for people in the field of life science research and biomedical industry.
Why did we attend the conference?
Since we determined the direction of the project, our team begun to conduct deeper studies on exosome. After looking up a considerable amount of literature and studies information in relevant websites, we learned about the workshop organized by the Bioon, which a large number of experts studying exosome attended. Dozens of experts presented their findings and offered their own insights on exosome therapy. Therefore, we learned much more about the latest information on exosome treatment on diseases.
What did we learn from this conference?
During this conference, we got to know many experts in the field and had in-depth communication with five of them. See more about our gains down below.
Dr. Hui Yu:
Characterization of exosome surface membrane proteins.
So far, the particle size and the semi-quantitative determination of particle size by means of immunochip capture and surface plasmon resonance (SPR) combined by exosome single particle imaging technology Dynamic analysis. However, the elution of exosomal antibodies and further purification of specific types of exosomes have not been formed by means.
Prof. Shenglin Huang:
In the process of producing exosomes, it is necessary to pay attention to the mycoplasma infection of the supernatant.
There are two known methods to deliver exosomes as drugs, one is by encapsulating long-chain RNAs, such as mRNA, circRNA, and incRNA, and another by miRNA-based microRNAs. In terms of principle and experimental difficulty, the more mainstream method is to package microRNA.
Protein modification on the surface of exosomes has obvious tissue specificity, and the internal tissue will also carry part of tissue-specific RNA, which may have certain effects during drug delivery and need to be considered separately.
Prof. Bifeng Liu:
At present, there are various methods for purifying exosomes on the market, but in general, the best effect and higher purity is still ultracentrifugation.
The microarray and the microfluidic chip can be used for rapid processing analysis of biological samples, and exosomes with specific membrane proteins can be purified by cell modification using chemical modification, immunocapture, and exosomal release.
The purified exosomes have been shown to inhibit tumor growth and metastasis to some extent by experiments in clinical lung cancer patients.
Prof. Yanlian Yang:
Various advantages and disadvantages of common methods of exosomes separation.
In vivo experiments on neurodegenerative diseases, miRNAs in cerebrospinal fluid are preferred for the selection of biomarkers in exosomal analysis.
The target of molecular chaperones produced in the brain and tau protein has an important correlation with the pathological development of Alzheimer's disease.
-
Prof. Yue Wang:
Pathological diagnosis of Alzheimer's disease: Find the corresponding biomarker in place of Abeta in peripheral blood.
The detection of mRNA in exosomes can be verified by transfection of probes or molecular beacons into the exosomes.
HEK293T and other cell lines are usually used in producing exosomes, and the cells used should not exceed five generations. Generally, the cells of 3rd - 5th generations have the best effect.
Through this meeting, we were more certain that using exosome as an envelope for our drugs is feasible.
2019 International Conference on Cell Therapy
On May 18th, XJTLU-CHINA & iGEM Club members participated in the International Conference on Cell Therapy organized by Bioon.
Why did we attend the conference?
During the exosome conference, we received great help and gained a more comprehensive understanding on the functions of exosomes, which greatly advanced our project. At the same time, our project has a lot to do with cell therapy. By attending this conference, our team hoped to learn more about cell therapy and made breakthroughs in related aspects. With this in mind, we hope that not only the members of iGEM team could participate in the meeting, but also more students in XJTLU could gain more knowledge from the conference.
What did we learn in the conference?
On this meeting, to our surprise, we learned a lot about the regulatory principles of drug launching. We happened to learn from a lecture delivered by Dr. Xiaodong Song titled "Comparison Of Chinese And American Cellular Drug Regulations and Industrialization Status". Thanks to Dr. Song and this lecture, we have a basic understanding about the drug-related administration laws and registration regulations both in China and the U.S.
After the conference, we had a deeper understanding on the laws and regulations that can be applicated into our project. We found that there isn't local laws or regulation that 100% fit our project. To solve the problem, we decided to use the regulations related with cell therapy, or CAR-T. Although it's different with our project topic, it's a stricter criteria since exosome is a safer approach than the CAR-T therapy. "Key points to consider for application of cell therapy products for clinical trial pharmaceutical research and application data" is considered an industry standard in the cell therapy issue.
The following file is the feedback we got from the conference, hoping to give future teams some helps.
Laws_and_Regulation
The 3rd iGEM Nanjing Regional Meetup
On 19th May 2019, we were invited to attend the 3rd iGEM Nanjing Regional Meetup held by the CPU_CHINA iGEM team.
Why did we attend this meetup?
In the Shanghai conference in April, we discussed and learned a lot from other iGEM teams. Since there are limited number of iGEM teams from Suzhou, we hoped to get to know more teams and exchange ideas with each other. Therefore, we decided to take part in the Nanjing Meetup.
What did we learn from the meetup?
The working principle of our project is similar to that of the CPU-CHINA project. In this meetup, we discussed the problems present in the experiments and other parts, and gained a lot of experience from the others.
Consultation with Dr. Xiaowei Hu
On 2nd of July, two of our team members had a communication with Dr. Hu in the First Affiliated Hospital of Suzhou University.
Why did we consult Dr. Hu?
Dr. Hu is a neurologist from the First Affiliated Hospital of Soochow University. After attending the two conferences and consulting large amounts of relevant literature, we started the overall experiment design. In the process, we found that we still had some problems in the etiology, pathogenesis, clinical detection and diagnosis of some neurological diseases. We hoped to find a brain surgeon to advise on the design of our project. After consulting our PI, we found that our project research area corresponded to the neurology section. So we contacted Dr. Xiaowei Hu.
What did we learn from the consultation?
Dr. Hu is an expert in treating epilepsy. We talked about many aspects about epilepsy. And the current medicine has certain effects on epileptic diseases.
According to him, we knew that the causes of epilepsy include birth injury, traumatic encephalitis, dementia and so on. The risk of death from epilepsy is two to three times higher than a normal person. Most of the deaths were non-accidental. The specific direct cause of death is unknown, and the affected sites in the body are not clear. Moreover, epilepsy can spread, and the disease can turn into multiple focal epilepsy, making the risk of death greater.
In addition to the patient's medical history, the doctor not only has to observe the patient's onset time to diagnose epilepsy, but also through EEG, CT, MRI or direct genetic testing. Epilepsy may be hereditary. In addition, blood tests can be performed on patients to measure their blood routine, liver and kidney functions to exclude the possibility of epilepsy and assess the safety risk of medication. Patients may develop drug resistance, and for a single drug, patients have a 40-50% chance of developing resistance to the current drugs.
There are two main types of treatment for epilepsy. The first type is treatment with drugs, such as oral or superficial intravenous antiepileptic drugs. Its functions include affecting the release or degradation of neurotransmitters, interfering with ion channels, or affecting prominent vesicles. The second type of treatment is non-drug options, such as surgical removal of the lesion. When using drugs, factors such as patient resistance to different drugs and allergies need to be taken into account. Even with oral drugs, 30% of drugs cannot enter CSF because of the blood-brain barrier. When the effect of drug therapy is not obvious, non-drug means can be considered.
If we want to conduct clinical tests on our drugs, we should first give them to normal people to measure the effect of drugs on human metabolism or the cytotoxicity associated the drug. But clinical test success rate is actually quite low.This is one of the problems need to be solved in the future.
After the consultation, we had a better understanding of the diseases, which helped us a lot in the future design.
Workshop at Youth Museum
In July 2019, we held a science workshop titled "my brain will discharge" in Suzhou Science & Technology Museum for Youth.
Why did we hold this activity?
As we focused on the reading of journals and news reports related to neurodegenerative disease, we found that there’s a huge gap between the understanding of the general public and the scientific fact of the diseases. Therefore, we chose epilepsy, which have a relatively high fatality rate among children, as the workshop topic. We hoped to promote correct understanding of epilepsy among the youngsters and their parents.
How did we conduct this activity?
The workshop focused on the definition, characteristic, pathogenic factors, treating method of the serious nervous disease: the epilepsy. It also contained how we should treat the patients with epilepsy and what should we do if we come across these patients, which is the first-aid method of epilepsy. There were about 100 attendees, including primary school students and their parents. In our lecture, we employed a video briefly introducing epilepsy and interactive demonstration for the audiences.
What did we obtain from the activity?
The teachers at the museum and the audiences gave good reputation towards the lecture, for it introduce this “esoteric” topic to the public very concisely. It provided the public with solid knowledge that can’t be easily learnt from the media.
Consultation with Dr. Yan Kong
On 18nd of July, two of our team members had a communication with Dr. Kong in the First Affiliated Hospital of Suzhou University.
Why did we consult Dr. Kong?
We would like to explore our project in greater depth from a clinical perspective. In the preliminary work, we improved our project by searching the literature and consulting with some professors. Therefore, we would like to consult relevant physicians to determine the feasibility and significance of our projcect.
What did we learn from the consultation?
According to the doctor, the early stages of neurodegenerative diseases are like a garbage can. Lots of neural diseases at early stage, which are poorly studied and classified, are all regarded as neurodegenerative disease. In this regard, doctors couldn't prescribe drugs accordingly for this complication.
Neurodegenerative diseases such as Alzheimer's disease are difficult to diagnose at an early stage. Only when the disease is in the middle stage or later can the doctor judge the disease by clinical cognitive diagnosis, which belong to the field of psychology.
Besides, the Parkinson's disease can be diagnosed initially with a drug. If the symptoms get relieved after taking the drug, then the patient is diagnosed with Parkinson's disease. But if the symptoms do not get better after the drug, that's Parkinson's syndrome.
Up to now, there's no effective diagnose method and treatment to the early stage of dieases. Even a final diagnosis was made in time, and there may not have good targeted drug therapy.
After the communication with Dr. Kong, we had a deeper understanding of the current clinical treatment of neurodegenerative diseases. Though up to now, early treatment is very difficult. If our project can be fully completed, it will be a great boon for early stage patients.
The 6th Conference of China iGEMer Community
From 18th to 23rd of Auguest 2019, two of our team members participated in the 6th Conference of China iGEMer Community in Shenzhen.
Why did we attend this meetup?
CCiC is the biggest iGEM meetup in China. By attending this meetup, we communicated with most of the Chinese iGEM teams. Also, in this meetup participants ultilized presentation, poster demonstration, and this could be a rehearsal of the Giant Jamboree in advance.
What did we obtain from the meetup?
At this conference, we got to know two teams: Nanjing Foreign Language School (NFLS) and the University of Chinese Academy Sciences (UCAS). We set up an ethics panel together and each team would interview local hospital ethics committees or professors who study in this field so as to learn their views on synthetic biology. After the interviews, each team shared their results to make up a larger sample size. Our team interviewed the ethics committee of the Suzhou Municipal Hospital. For details, please go to our safety pageethics and safety in medical RNA molecules part.
Ethics consulting
We consulted Prof. Minyan Wang for some ethical questions.
Why did we consult Prof. Minyan Wang?
Prof. Wang is a member of the XJTLU Research Ethics Committee. After attending CCiC conference, we realized that we need to learn more about ethics for better justification of the ethical issue of our project. We hoped that Prof. Wang could give us some guidance about it.
What did we learn from the consultation?
Prof. Wang told us that having an effect on brain neurons or glial cells was inevitable in terms of brain therapy. But this issue had no sense in ethics. If a medicine would make the biont have its own ideology, or the medicine is addictive, the medicine had ethical issue. According to this situation, our project have no problem in ethic.
Reflection
Patients Interview
Why did we interview patients?
The patients are our stakeholders. We need to know what they think about the disease and their expectation about the disease. In addition, we need to know whether their condition will be improved by the drugs and their experience with the drugs. We can learn the value of our project from patients.
What did we learn from our interview?
We found that patients were terrified when they first learned they had neurodegenerative diseases with no cure. They didn’t know much about the disease and often missed the early stages of treatment. The drugs they used now have side effects, such as a bad cold. The drug currently in use is an anti-anxiety drug, the antimicrobial fluoxacin, for treating pressure sores. The drug helped ease the condition of forgetting. They hoped that in the future there would be government intervention and special teams to care for patients. They also hoped future drugs would help patients stay awake and take care of themselves.
Questionnaire
We designed a questionnaire to ask the public about the safety, ethics and feasibility of our project and received a total of 306 responses.
Why did we do the survey?
Our project was drawing to a close. After communicating with patients and their relations, we wanted to know the thought of the public to our project. So we made the questionnaire.
How did we publish the survey?
We made a video to introduce our project and published our questionnaire with the video by tweeting on our Wechat public account. At the same time, to allow the public to gain a better understanding of our project, a brief introduction on neurodegenerative diseases was also written in the tweet.
What did we learn from the survey?
The questionnaire spread widely in the school. We also invited some professors to watch the video and filled out the questionnaire. From the questionnaire, we could reach some conclusive views from the answers. For example, some answers advised that we should add certain specific targets. This issue was considered in our design of the plasmids regulation system model. At the same time, the feasibility of our project was accepted by the public. Furthermore, they also gave opinions in the safety and ethic parts.
Below is the video.
You can read the report for more details about the results of our quentionnaire.
ReportExpectation
Consulting about drug launch
We consulted the Marketing Department of Hengrui Medicine and Dr. Chunmei Fu, who is a professor at the West China School of Pharmacy Sichuan University, about the issues related to drug marketing.
Why did we consult them?
We hoped we can know more about drug launch procedure. And drug launch is closely related to most pharmaceutical companies. Therefore, we hoped to get in touch with the companies to obtain relevant information, to make our drug better meet the criteria of the market. At the same time, we believed that the doctor in the West China School of Pharmacy Sichuan University had her own view about drug launch. So we consulted Dr. Fu.
What did we learn from the consultation?
Firstly, we contacted the marketing manager of Hengrui Medicine, which is a medical and health enterprise engaged in pharmaceutical innovation and R&D production and promotion of high-quality drugs founded in 1970. The manager kindly gave us two documents, respectively about the process of drug development, clinical trials and marketing, and a draft plan on market operation mode. This is a great help to our simulation system.
Secondly, we had a better understanding about the procedure of drug launch in China thanks to Prof. Fu. We foresee where this project would lead us in the next approximately 20 years. It helped us better understand the difficulty in drug development and motivated us to work harder on it for a better life of all human.
Drug simulation launch system
Why did we want to simulate drug launching?
At the beginning of the iGEM year, we chose therapeutic project as our final goal. This is because our team members have a dream to invent drugs to treat diseases. We hoped to make a drug successfully to alleviate the symptoms of neurodegenerative diseases, but due to the pressure of time limitation and experimental conditions, we stopped our project at the function verification of EAAT2 protein. We deeply hope that we can get this drug launched into the market to help patients, so we chose to build a drug simulation launching system that we hope will guide future projects.
How did we process it?
We consulted the marketing manager of Hengrui Medicine and Prof. Fu at the West China School of Pharmacy Sichuan University about the relevant issue on drug launch, which was a great help to our project.
Below is our simulated plan of drug launch.
Drug launchThe iGEM club
Why did we set up this club?
The iGEM XJTLU-CHINA team has been set up since 2016, despite it has received good score every year after the Boston competition, it is still not very well-known within our university campus. Therefore, this year we decided to enhance the influence of the iGEM competition and synthesis biology at XJTLU. At the same time, we provide students with a platform to develop interests and skills in out-of-class science.
How did we develope this club?
In March of 2019, we recruited more than 40 club members in our Spring recruitment, including 9 managers. That’s when our story began. From March to October, we organized activities to let students attend the two Bioon conferences with discount prices. Also, we helped setting up ‘the XJTLU Internship Base’ in the Suzhou Science & Technology Museum for Youth and sent about 100 volunteers during the summer vacation and the autumn semester. We also organized on-campus club activities like the iDreamer and other scientific workshop introducing the latest scientific hot topics or demonstrating some fun experiments like purification of cyanobacteria, making hand cream, and so on.
We also set up an iGEM-XJTLU-CHINA Wechat official account. In 10 months of time, we posted more than 50 posts, in which we advertised our club activities, promoted the concept of synthetic biology and other latest scientific researches. On the World Alzheimer's day, we also posted a tweet to call on the public to pay more attention to this disease and the care of the patients. Up to now, we have more than 500 followers and is increasing constantly.
What did we get from the club?
By setting up the iGEM Club, we obtained a growing influence and attention inside XJTLU. The club members also offered great help to the team HP work, for example, maintaining the daily update on social media. More importantly, the collaboration and resources that we got can be well utilized by the Club. In the future, we would keep on working with the iGEM Club, dedicating to the popularization of synthetic biology and iGEM competition in the university and the society.The iGEM Club will be existing from now, providing a good linkage for the continuation of HP work.
