Team:Tongji Software/Human Practices

  • Investigation
  • Exploration
  • Improvement
  • Out of the campus
  • Words in the end

HUMAN PRACTICES



We always believe that communication is mutual. In the whole human practice part, we improve our project through exchanges with the public, biology experts, doctors and synthetic biology related enterprises. In this process, we also promoted the dissemination of synthetic biology and the construction of iGEM community. Thanks to those who have communicated with us and put forward suggestions. Because of them, our project is getting better and better.


Fig. Brief Summary of Human Practices


Investigation -- Social demand & Our Birth


Questionnaire

At the beginning of the project, in order to understand the public's cognition of synthetic biology, phages and drug-resistant bacteria involved in our project, we made a questionnaire to count the relevant results to guide our follow-up Human Practice and communication. We have collected 858 questionnaires from all over China, most of whom had a bachelor's degree or below. However, in view of safety, in our questionnaire, the public can decide whether to fill in the information of educational level, and we only collect this personal information for knowing the real public's awareness of our project and related knowledge.



Public understanding level of relevant knowledge


Fig. Public understanding level of relevant knowledge


From the Figure, we can analyze that most people do not know much about synthetic biology, phage, superbug and phagotherapy, so our popular science is extremely urgent and of great significance.

At present, 27% of people know about synthetic biology through articles, while 25% of people understand it through schools, and the proportion of people through lecture and public science institution such as museum to know about it is not high. Thus we decided that our way of doing science popularization is mainly publicized by articles sharing, WeChat official account, and school cooperation, etc.



Public attitudes and views



Fig. Public attitudes and views


At the same time, we also investigated the development attitudes of people to related directions. It can be seen from the above figures that most people don't have a clear view on the development of phage therapy. We think the main reason is that they don't have a full understanding of this aspect. So, we actively carry out communication with the public, and we pay more attention to science popularization video production and article writing. Because form the results, we can know the public have a higher acceptance of them.

Generally speaking, through the preliminary questionnaire survey, we realized the public's demand for popularizing knowledge on synthetic biology, phage therapy and superbug. These data encouraged us to carry out relevant communication with public at the far beginning of our design, and has always provided guidance for the development of our work throughout the whole project.


Communication with Dr. Lv

We had an exchange with Dr. Lv of the school of life sciences and technology of Tongji University. At the begining, our team leader Yanping Zhao introduced our project to Dr. Lv. During this period, we discussed a lot about the project model and bacterial diseases. In the end, she held positive attitude toward our project and believed that it could promote phage therapy to a certain extent.

Fig. Communicate with Dr. Lv


It's worth mentioning that during the communication with Dr. Lv, we discussed the topic of biofilm. In order to resist the external adverse environment (antibacterial substances, etc.), different bacteria often gather together to secrete substances to form a membrane to wrap themselves and isolate the external environment. And also, Dr. Lv pointed out that lysin secreted by phages may have a certain dissolution effect on biofilm. So, Phage therapy may have a good effect to biofilm, and we are more confident in our own project.

The communication with Dr. Lv made us realize that there are certain expectations in the scientific community for phage therapy. Thank you very much for your sincere help!



In summary, by learning about the needs of the society through questionnaires and actively communicating with Prof. Lv, we realized that researching phagotherapy made sense. Therefore, our project, Phage-Map initially born.


Exploration - Social feedback & Our Design


Communication with Dr. Liu

After knowing the public demand, we actively discussed with Professor Qi Liu from The School of Life Sciences and Technology of Tongji University to finalize the direction of the project. It was the discussion with Professor Qi Liu that led us to initially confirm the CRISPR-based approach to measuring strength of phage-bacteria interactions.

Fig. Communicate with Dr. Liu


Anyway, throughout the project, Professor Liu qi also gave us lots of good suggestions, such as "it will be clearer to visualize the results in network graph"," in order to promote the research in this field, establish a database to share the data". It can be said that the communication with Professor Liu Qi determined the general direction and functional modules of our projects. Thank you, Prof. Liu!


Academic conference about phage

In July 2021, 4th Superbug Infection and Bacteriophage Prevention Summit was successfully held in Fudan university. There were 5 phage-related topics, including prevention and control of severe bacterial infection, bacteriophage omics research, bacteriophage clinical therapy, bacteriophage ecology, bacteriophage and host bacteria frontier research.



Fig. 4th Superbug Infection and Phage Therapy Summit


We participated in it both online and offline. At the scene, Yanping Zhao, the team leader of Tongji_Software, proposed whether our project concept of "detecting spacer based on CRISPR system, and then detecting interaction between bacteria and phage" is feasible. We got a positive answer to this question, because the participating experts had already adopted this idea when doing the research work on soil chromium pollution.


Fig. Yanping Zhao was asking question



After receiving multiple responses from the society, we confirmed that the idea of the project at that time, "study phage-bacteria interaction", is valuable. To our delight, the academic community has paid close attention to phage-bacterial interactions and phage therapy. The program we developed about CRISPR-spacer was also accepted by the society, which strengthened our determination during the exploration phase.


Improvement - Social opinions & Our Perfection


After confirming the correctness of the basic principles of the project, we started our work. Not communicating with the outside world tends to make people stuck in their own ways and not take objective circumstances into account. So, in the process of work, we also actively contacted the outside world and got some very great suggestions.


Communication with SJTU-Software

On August, because the result of our preliminary project design is not good. So, we had offline communication with SJTU-Software for asking their help. During the exchange, SJTU-Software put forward valuable opinions to us: they suggested that we try non-alignment method. It was with the suggestion of SJTU-Software that we added the alignment-free method, the core of the project was supplemented, and the whole project was more complete.


Fig. Alignment-free Method


And, in addition to the project, we also exchanged many questions about synthetic biology. Similar age makes us have more topics to communicate, and the whole process is more active. For more details, please click partnership.


Fig. Communication with STJU-Software




Communication with Professor Du and Professor Guo

In August, we talked about our project to two professors, Prof. Du and Prof. Guo, and asked them for some advice. During the meeting, the two professors put forward many suggestions to us, for example, "let's pay more attention to the validation of software", "English should be used, which is conducive to the dissemination of knowledge". Professor Zhanyun Guo also pointed out that "we should distinguish lysogenic phage and lytic phage", "We should think more about the target users of the project" and "how should we show our project in a way that's easier for the audience to understand". These valuable suggestions have benefited us a lot. In particular, the proposal to distinguish lysogenic phage and lytic phage directly allows us to make up for a loophole in the project.

Fig. Communication with Dr. Du and Dr. Guo




Out of the campus - Come to the society



We obtained a lot of great guidances from experts and academic conferences in the field of biology. Our communications with them made us find and fill some small loopholes in the project. For example, we paid more attention to finding the verification dataset and the detection effect of the final software. With their suggestions, we completed the project better, but we wanted to have a deeper understanding of the clinical application prospect of the project, not just from the literature report. So, we had some exchanges with clinicians, mainly to discuss the clinical application value of our project, hoping to provide a certain reference for clinical treatment.

Shanghai Dongfang Hospital

Fig. From left to right, Dr. Zhou, Dr. Zhang, Dr. Su, Xingbo Yang of Tongji_software


Shanghai Dongfang Hospital (Dongfang Hospital Affiliated to Tongji University) is a large class III, comprehensive hospital integrating medical treatment, teaching, scientific research, first aid, prevention, rehabilitation and health care. In communicating with them, they expressed their interest in our project. Because many patients in the hospital did not have a good treatment plan when they were infected with superbug. Traditional antibiotic treatment often has side effect. So they are looking forward to our software can be further improved to provide a certain reference for clinical treatment.


During the exchange, medical professionals expressed frustration over the superbug problem. Considering the urgency of superbug treatment, we conducted immediate adjustment for our project. We separately extracted the superbugs dataset from our completed database, then specially established a more detailed analysis process for it, additionally appended the MAP module.




Delonix Bioworks

In the process of communicating with the public, experts and lovers of the same age, our project was becoming more and more perfect. However, in our opinion, synthetic biology is a science close to life and a discipline to be industrialized. So, only academic exchanges are not enough. We also need to communicate with the industry, such as synthetic biology companies, hoping that they can give us some suggestions and help from the perspective of industrialization. With this purpose in mind, we had an exchange with Dr. Lin qiubin, chairman of Delonix Bioworks.


Delonix Bioworks is a very young synthetic biology company. Founded in late 2020, and headquartered in Shanghai, China, Delonix is committed to developing innovative vaccines and live drugs for infectious diseases and cancers to meet global public health safety challenges through innovative approaches to synthetic biology. Its synthetic biology and antigen discovery platform can rationally design and reprogram pathogens, so as to quickly develop safer and more effective vaccines. The company's performance in the capital market is particularly excellent. Shortly after its establishment, it received heavy support from well-known investment funds such as Boehringer Ingelheim risk fund (BIVF), IDG capital, Zhenge fund and other well-known investment funds.


Fig. We are in Delonix Bioworks


On October, 2021, we came to Delonix Bioworks and showed our project: Phage-MAP website. During the communication, Dr. Lin mentioned some limitations of phagotherapy in clinical application. For example, it is difficult to make a patent medicine, and the composition of infected bacteria in each person's wound is inconsistent, so a personalized phage medication scheme is needed. However, he also mentioned when a person is on the verge of being infected with superbugs, Phagotherapy may be the last hope. In the end of communication, he said:" You've done a good job".

It's worth mentioning that Dr. Lin, the boss of the company, was the first member of iGEM in China. He asked about the current situation of iGEM and our team. When talking about the iGEM competition, Dr. Lin said that most of the founders of Companies in the field of synthetic biology in China are associated with iGEM. And, he encouraged us to contribute to synthetic biology in the future. Then we visited the company's laboratory.


Fig. We are visiting Delonix's laboratory


In a word, through contact with Delonix, we learned the most real feedback from the industry. And we were affirmed by Dr. Lin, which was exhilarating. In the future, we will consider how to make the project closer to production.



Send your message

It's really, really worth mentioning that our project website: Phage-MAP was designed with human practice in mind. At the bottom of our project website, we set up a message box. Here you can submit suggestions for our project (including page design or what you want us to add or improve). We will carefully read and analyze this information, because we truly believe that perhaps a short message can make our project better. At present, we have received many messages, many of which are sincere suggestions and, of course, encouragement to us.

Some bugs mentioned in the message have also been improved. For example, someone told us that we should add recommended items and fuzzy search in the search bar of Phage Finder module for more convenient use. We thought this suggestion was a very good idea. Although at first, we thought it was easy to implement, it took us two full days to achieve this function.



Fig. Feedback from the website



Words in the end, words for the future


To sum up, our HPs are not a loose group of social activities independent of the project. At the beginning of the design of HP scheme, we considered how to combine it with the design and promotion of the project. After the discussion in the team, we determined the basic idea of HP: Guide our subsequent communication module through the questionnaire, improve the subject design through the information obtained by HP, improve our model and understand the actual needs of phage therapy through HP communication. Of course, all our HP are strictly in accordance with the relevant safety guidelines.


Fig. Intergrated HPs


Questionnaire

Through the questionnaire, we learned about the public's cognition of synthetic biology and phagotherapy, and which form of popular science do they prefer to accept. These statistics prove that our publicity and popular science is very necessary.

Background

In the initial project, we consulted teacher Dr. Lv of Tongji University who held a positive attitude towards the content of our project. With communicating with Professor Qi Liu, we found that recommending phage therapy based on CRISPR-Cas system is a good application scenario. After attending the Phage Summit Forum, we asked about the feasibility of determining phage bacterial interaction based on Spacer, and got a positive reply from the participating experts.

According to the information obtained by HP and the brainstorming within the team, we determined the specific direction of the project: by adopting CRISPR-Spacer-based method, measured the strength of bacteria-phage interaction to recommend candidate phages in phagotherapy.



Model Improvement

After determining the research direction, we used spacer sequence alignment to study the interaction between phages and bacteria. After getting the preliminary results, we found that the detection rate of the model was too low. To solve this problem, we had a discussion with SJTU-Software. Their sentence reminded us: why not try the alignment-free method.

Therefore, we added the alignment-free method to score by using the Gaussian distribution of k-mer and the similarity of k-mer Markov model. Combining the alignment and alignment-free methods, the test result of this design turned out well.



Design

During the discussion with Professor Guo and Professor Du, they put forward many suggestions, including "the need to distinguish lysogenic and potent phages". In the follow-up results, we selected lysogenic phages and retained only potent phages to obtain better practical efficacy.

In the communication with doctors of Dongfang Hospital, they said they expected our project to play a guiding role in the treatment of superbugs' infection. For superbug, we specially designed a module to show the relationship between superbugs and interacting phages, Interactive MAP. It is convenient for clinical application.



Ending Words

During Human Practices processing, we embraced voices from all directions, at the same time contributed our insights and achievements on phage-bacteria interaction to society, and spread our passion for iGEM and synthetic biology. We are deeply aware of the enduring and close relationship between scientific research projects and human society. In the future, our programs will evolve toward more general and precise goals, applying the achievements to medical and industrial applications. It's an endless journey for us.