Partnership with iGEM WHU-China
Earlier this year, we contacted iGEM WHU-China because, initially, we brainstormed two project plans, and one of them centered around Major Depressive Disorder (MDD). Similarly, iGEM WHU-China also focused on MDD this year. In their project, Reach for Light, team WHU-China designed their engineered bacteria to secret a natural anti-depressant, SAMe. We shared our preliminary designs in the first meetup on March 19th and picked up on one another both academically and personally.
Although we chose to take our work in the diagnostic and therapeutic approaches to Autism Spectrum Disorder (ASD) further after our revisit to a rehabilitation center for autistic children, unfortunately, we still kept in contact with WHU-China. Our two teams agreed to build further partnerships throughout the season since we were both focusing on treating neurological disorders with the help of gut-microbiota-mediated metabolites. From brainstorming to the launching of our projects, we supported one another at different stages and made progress together. We also contacted each other through Tencent QQ, a popular social media platform in China, whenever problems occurred. Each of us hosted three online meetings, and in these six sessions, we shared our design, modeling, and human practices and posed questions during the process. That enabled us to see our problems and make modifications accordingly.
Wet Lab
Our collaborative work in terms of wet lab included project design, experiment design, troubleshooting, and research techniques. Besides the first meetup, we held another online meeting after our team developed our primary design for treating ASD by improving mitochondrial function. During our discussion, members from team WHU-China asked us about the exact substances that we wanted our engineered bacteria to secrete. In this regard, we explained our initial idea of developing a cocktail of nutrients to fix mitochondrial dysfunction. They advised us to engineer our bacteria to produce only some or even one of the many elements that are of the greatest importance to make for the feasibility of the project. Additionally, upon sharing our plan for designing a testing strip by sensing lactic acid, they suggested that we could make an accurate reference color card with modeling. This inspired us to work further on the container of the testing strip during our work in Hardware. They also reminded us to rule out other conditions that might lead to an increase in lactic acid in the urine, which we studied deeper after the meeting and, in an effort to demonstrate the feasibility of using lactic acid, calculated the theoretical maximum amount in other situations with statistics from a wide variety of literature.
At the same time, we talked about our experiences in culturing different types of bacteria and learned about the modifications each of us made to the standard techniques. We also offered them our ideas on treating MDD from a medical perspective by explaining the pharmacodynamics of some commonly used anti-depressants, which inspired them to think about mimicking the natural drug uptake with an oscillator.
Human Practices
Concerning education, we worked together and organized four lectures online, educating university students on MDD, ASD, psychological and neurological disorders, and the human brain as a whole.
In the first lecture, our team shared some new findings concerning the pathogenesis of ASD, including both genetic and metabolic factors. We specifically discussed the role of mitochondrial dysfunction in the development of ASD. In the second lecture, we invited Professor Zhilin Wang, a professor from the Jiangsu Research Center for Mental Health, to offer us some advice on maintaining a good mindset. He also talked about the similarities and differences between psychological and neurological disorders, giving listeners a better understanding of ASD and MDD. At the end of the lecture, Professor Wang introduced the idea of neurodiversity and expressed his wish for more respect for autistic people on this special day.
Our educational lecture on mental health
After that, team WHU-China informed listeners of the possible causes, symptoms, and treatment of MDD and called for mental health awareness. They also invited Yaya, who is the co-founder of Sailing through Adolescence, an organization dedicated to supporting young people with depression, to join us in the fourth lecture. Yaya educated us on MDD from a medical perspective, discussing the neurological factors behind each disorder.
Educational lecture on ASD & MDD
At the end of the lectures, we handed out questionnaires and reflected on the content and delivery of our lecture to improve and modify. We hope that through the four lectures, more people will love, support, and respect people with ASD and MDD.
Questionnaire made by iGEM WHU-China
On September 12th and 18th, we held two online meetings centering around the related regulations and possible approaches to entrepreneurship, respectively. Since neither of us is familiar with the procedures of commercialization, these online meetups were an excellent platform for both of us to learn about entrepreneurship and make progress together.
Modeling
We also worked closely with each other in terms of modeling. Besides regular discussions on the problems that we came into, we also held an online meetup in July, during which we shared the work that we have completed regarding mathematical and physical modeling. iGEM HZAU-China also joined us in the meetup and discussed the models that they applied to promote their wet lab experiments.
We realized that determining appropriate parameters was a frequently occurring problem for all of us. After thorough discussion, however, we realized that as long as we keep track of the magnitudes, we will be able to fit the ODE without specific parameters. In addition, team HZAU-China inspired us to testify, predict, and even modify experimental conditions through certain models. Specifically, we decided to ascertain the relation between metallothionein (MT) and the expression of our target RNA through fitting, and determine the parameter with the help of machine learning instead. We were also glad that our work in building a 3-D model inspired team WHU-China to construct new models with software, such as Blender, to visualize the intestinal inhabitation of their engineered bacteria.
Online meetup on modeling
It was also during this online meetup that we came up with the idea of building an online platform where each team member can post their questions or provide their answer to an existing question. Users of the platform can either ask a question that they met during wet lab work or modeling, or share their experiences in these areas. Initially named the Intestinal Association, the platform was maintained and used by three teams: iGEM WHU-China, iGEM NJMU-China, and iGEM HZAU-China. Apart from the contacts, introduction, and design of each team, a discussion board was also set up for free discussion on the new findings related to intestinal microbiota.
Educational lecture on ASD & MDD
Partnership with iGEM NAU-China
We established a partnership with team NAU-China, another team from the city of Nanjing, based on the close relationship that we had established during the 2021 iGEM competition. After determining the subjects that we plan to focus on, we decided to go further into collaborative work because both of our works included the diagnostic approaches to a certain condition. Team NAU-China is working on the early detection of hepatitis. Their project, Liver Monitor, is a rapid cell-free detector of liver diseases based on bile acid levels. Since we are also trying to build a detection system in the form of testing strips, we figured that it would be beneficial for both teams if we collaborated throughout the season.
Together, we held four online meetups before finally meeting offline. In these meetups, we supported each other in terms of project design, human practice approaches, and especially modeling. We will present the details in chronological order since each of our meetings contained discussions related to all the abovementioned aspects.
April
In our meetup in April, team NAU-China and we talked about the topics that we had decided upon. We also introduced the backgrounds of each of our projects, through which we were able to have a better understanding of both Autism Spectrum Disorder and liver diseases. Team NAU-China suggested that we should focus on a specific aspect of autism treatment and keep our project “tight.” This inspired us to design our project to fix mitochondrial dysfunction and develop our projects into four related subsets.
We are glad that we helped them with our knowledge as medical students as well. Apart from explaining the pathophysiological mechanisms of different types of liver diseases, we also introduced the epidemiological backgrounds of the five types of viral hepatitis. Moreover, we suggested that they could focus on hepatitis C instead of hepatitis A when studying the background since infections with HCV are more likely to turn chronic.
Online meetup with iGEM NAU-China in April
June
We chose to hold another online meeting in June because, at that time, both of us had already developed a relatively mature design. During this session, we explained our projects in detail and discussed the safety measures we had taken or planned to take. A great challenge that we encountered in this period was that our plasmid for the urine testing strip was too large for a kill switch to fit in. Hearing about this, team NAU-China shared articles on relatively small kill switches that they read about in an effort to help pull us through. Although we did not solve the problem by adding these kill switches (more details are available in the Safety section), we were still appreciative of their genuine concern.
In addition, we discussed possible human practice activities that we could organize together in the months to come and planned to design our team merch together.
July
Our collaborative work in July mainly centered around modeling. Team NAU-China offered some tips on building 3-D models of the proteins that we were working on. They also talked about some useful tools for modeling, which was very informative.
Team NAU-China's protein model
We also updated the latest progress that we had made in wet lab experiments and shared our gene circuits as well.
August
During our offline meetup in August, we shared our projects again after the modifications in the previous months. Regarding our approaches to preventing the accumulation of heavy metals, team NAU-China asked about the possibility of the chelate being affected by the variation in pH. Moreover, we discussed the potential harm of the mazF protein to the epithelial cells of the small intestine due to its capability of triggering apoptosis in both prokaryotic and eukaryotic cells. Although both of us believed that the possibility of exogenous proteins entering a functioning cell is limited, we still dug into literature afterward and conducted experiments to verify our assumption. We were also inspired to test the endurance of our engineered bacteria in heavy metallic salt solutions. Since they planned to test the bile acids in the urine, we offered them some advice on the choice of urine samples as well.
Education-wise we both attended a meet-up hosted by iGEM NJTech_China and iGEM NNU-China at Nanjing jiangbei New Area biopharmaceutical Public service Platform on August 5th. The meetup offered a platform for us to share experiences and learn from one another in terms of education. Members from team NAU-China came to us during the breaks and together, we planned possible educational activities that we could carry out in the following months.
Education & Meetup
