HP

The development of MAP, from the birth of the initial concept to the continuous iteration and the addition of new elements in technology, is the result of ongoing two-way interactions with various stakeholder groups. We will present our HP (Human Practices) work by including the "Theme Explore Phase," "Preliminary Design Phase," "Challenging Breakthrough Phase," and "Detail Adjustment Phase."

Theme Exploration Phase (February-April)

1.The anxiety of acne brought us together

The attention to acne issues originated from a conversation on "troubles of the youth." We come from different schools in different regions, but all of us have noticed that many suffer from facial anxiety and some of our team members are even dealing with harassment due to their acne.Looking at this, we noticed that we had many shared feelings and observations towards acne.
"I don't have acne right now, but I have no idea about when it will flare up again."
"I don't think my acne leads me to anxiety, but others always make me feel like I should do something about it, which forces me to pay attention to it."
"Some of my classmates go crazy about skincare, and they visit beauty salons regularly."
"Sometimes I worry if my roommate's acne will infect me."
In this way, we gathered together because of the troubles of youth and began to pay attention to teenagers' skin problems.

2.Question to Society and Society's Feedback

Q1: Is acne a problem for a few of us or a common issue? How many people share our discussion results? Is there a market demand?
Action: We conducted a public survey questionnaire and we received valid responses from 439 participants.
Conclusion: Whether in teenagers or adults, many people have concerns about acne. When acne has not erupted yet, people don't know how to prevent it or when it will appear. And after acne does erupt, mainstream acne treatment products often do not work well, leaving the public helpless with acne.

3.Who cares about our anxiety? Nobody!

Q2：Who is currently dealing with acne problems?
Currently, cosmetic hospitals and doctors are focusing on this.

Action 1
Communication with cosmetic hospital
We had an interview with Yue Yu, the director and medical cosmetologist of Shenzhen Airuibutha Plastic Surgery Hospital.

Fig.1 President Yue Yu is listening to the member's description.

Feedback
In this interview, Dr. Yu introduced some prevailing acne-curing methods. According to Dr. Yu, fruit acid treatment and red & blue light irradiation are two common ways to deal with acne problems. However, these two methods are used only when symptoms have appeared, meaning that there are no preventative methods for acne on the market right now. Besides, the misuse of fruit acid will cause ulcers, redness and swelling of the facial skin.

Action 2
Communication with doctors
We communicated with Professor H, the director of Dermatology at the Hospital of Chengdu University of TCM, and doctor Jingjie Liu from the skin care and plastic surgery department of Yuquan Hospital, Tsinghua University.

Fig.2 Doctor Jingjie Liu from Tsing Hua University Yu Quan Hospital, Beijing (left) and Doctor Ying Huang,
the director of the Department of Dermatology from Affiliated Hospital of Chengdu University of Traditional Chinese Medicine.

Feedback
(1) According to doctors, acne is a clinical problem and it can be relieved by medicines only after symptoms appear.
(2) Prevention is recognized by doctors as the most effective way to cure acnes, but there are no preventive medications or skin care products clinically.
(3) By inquiring about the acne cases, we learned that with the daily pressure and lifestyle changes, the number of patients increase, among them not only teenagers but also many adults.
(4) What cause skin problems is usually some skin bacteria, the growth of which causes skin infections.

Conclusion
Therefore, existing skin care products and treatments are not effective and can cause problems such as damage to the skin barrier, drug dependence, pain and scarring. However, doctors in hospitals and cosmetic institutes do not have any accessible means of preventing this.

4. Finding “cracks”

After our group discussion, we had a concensus in original that bacterial infections in the skin might be a clue to help us solve this issue. We looked for an expert who is familiar with clinical treatment and also engages in basic research in order to learn how to achieve effective control of skin infections by controlling bacteria.

Action
We contacted with Professor Zhou from Luoyang Central for an online session. Prof. Zhou introduced us to Chinese medicine acne-curing methods and Western medicine methods of treating acne in this online seminar.

Fig.3 Prof. Zhou Haitao's online seminar.

Feedbacks
Prof. Zhou said that it is difficult for both Western and Chinese medicine to achieve "no acne" for a person. He admitted the feasibility and the innovation of our project. Besides, he also suggested that we focus on acinetobacter, which is the main cause of skin problems, and encouraged us to think outside the box of traditional Western medicine.

Conclusion
This led to our original idea - to configure and synthesize a Mix ingredient similar to a Chinese medicine, which is both antiseptic and skincare , but with clear ingredients compared to the ambiguity of Chinese medicine ingredients.

Product Preliminary Design Stage（May-July）

1. Paper review, sort out feedback, and discover that there is a huge problem!

After plenty of group meetings, we identified the following vital questions:
(1) the biology principle of acne,
(2) causes of acne
(3) how to prevent acne
(4) how to kill acne.

Action
To solve these questions, we did a large number of searches on Google Scholar, Q&A communities , Social platforms,and Video platforms.

Feedbacks
Finally, we found the following literature to answer the above four questions:
(1) the biology principle of acne,
(2) causes of acne
(3) how to prevent acne
(4) how to kill acne.

[1]McLaughlin, J., Watterson, S., Layton, A. M., Bjourson, A. J., Barnard, E., & McDowell, A. (2019). Propionibacterium acnes and Acne Vulgaris: New Insights from the Integration of Population Genetic, Multi-Omic, Biochemical and Host-Microbe Studies. Microorganisms, 7(5), 128. https://doi.org/10.3390/microorganisms7050128
[2]Draelos, Z.D. (2010). Examining Over-the-Counter Acne Treatments.
[3]Liu H, Yu H, Xia J, Liu L, Liu GJ, Sang H, Peinemann F. Topical azelaic acid, salicylic acid, nicotinamide, sulphur, zinc and fruit acid (alpha‐hydroxy acid) for acne. Cochrane Database of Systematic Reviews 2020, Issue 5. Art. No.: CD011368. DOI: 10.1002/14651858.CD011368.pub2. Accessed 06 October 2023.
[4]Sánchez-Pellicer P, Navarro-Moratalla L, Núñez-Delegido E, Ruzafa-Costas B, Agüera-Santos J, Navarro-López V. Acne, Microbiome, and Probiotics: The Gut–Skin Axis. Microorganisms. 2022; 10(7):1303.
[5]Gema Dura, Daniel T.Peters, Helen Waller, Adrian I.Yemm, Neil D.Perkins, Ana Marina Ferreira, Maria Crespo-Cuadrado, Jeremy H.Lakey, David A.Fulton.(2020).A Thermally Reformable Protein Polymer

However, we still do not know what methods or effective ingredients can address acne prevention safely. Everything seems to be beyond our capacity. Obviously we're stuck.

2. In the depths of our despair, we find the first light of day.

External Feedback
At the end of May, our team coach, Professor Pengcheng Fu, gave us a series of lectures on iGEM and synthetic biology. This helped us understand the purpose (aim) of iGEM and how to use synthetic biology to create the biological components we need, conduct bacterial testing, and even precisely capture and eliminate them. Professor Fu also affirmed the value of our project.

Fig.4 Professor Fu is giving a lecture about synthetic biology.

Action
Our team begins to conducting further experiments. With the guidance in original from Professor Fu, teacher Yanying Hua and teacher Yan Zhang from Hainan University's laboratory, we started learning laboratory safety regulations, searching from primers for ordinary PCR, and began conducting experiments to detect P. acne on human faces by using PCR.

Fig.5 Members are doing the PCR experiment.

Results
Successful detection of P. acne on human faces using ordinary PCR increased (boosted) our confidence. However, it also raised new questions: Are the faint bands in the P. acne detection results due to the absence of bacteria on the skin, flaws in the detection method, or is there a way to make the results more specific?

3. CCIC: We aren't the only ones troubled

Action
With questions about our PCR results, we attended the CCIC (Conference of China iGEMer Community) from July 8th to July 9th, 2023, where we shared and exchanged ideas.

Fig.6 BS-United-China is attending the CCIC (Conference of China iGEMer Community).

Feedback
(1) Our project received recognition at CCIC.
(2) Other participating teams chose to conduct P. acne PCR testing through third-party organizations, and their results were consistent with our PCR testing results conducted in the laboratory,validating our results.
(3) Conference members asked questions about how to handle P. acne once detected

Conclusion
We were pleased with our PCR testing proficiency and accuracy, but new challenges came up:
(1) Accurate detection of P. acne has technological limitations even in the market. How should this be upgraded?
(2) Now that we can detect it, how do we handle it? How can we ensure specificity? This is a critical issue, and currently, we have no solution.

At this point, we entered the challenging and lengthy phase of technological exploration and breakthroughs.

Challenging Breakthrough Phase (July-September)

1. We need new approaches and new concepts to replace traditional treatments

Action
confused,we consulted Professor Fu and Professor Austin Wu from Columbia University.

Fig.7 Remote meeting with Professor Wu.

Feedbacks
(1) Professor Wu brought L-RCA to our sight by giving us suggestions about whether there is an alternative to PCR with high fidelity.
(2) Professor Fu, on the other hand, proposed a new concept: whether it is possible to make a net to capture and bring P. acne out of the pores precisely.
(3) Professor Wu provided us with an investigation on Caf1.

New action and results
Under the instruction of Prof. Fu we constructed a combination of Caf1 with AMP antimicrobial peptide, and also read some articles about DNA linkage reactions on PCR problems.

2.Experts' feedbacks on BS Cleanser

After we designed a product that combines both the Caf1 and AMP antimicrobial peptides, we named it the BS Cleanser, and we hoped to receive feedback for this new product from experts.

Action
We had an online seminar with Professor Xin Zhang from Peking University Shenzhen Hospital.

Fig.8 Remote discussions with Professor Xin Zhang.

Feedbacks
(1) Professor Zhang argued that under our design AMP may be less effective due to the lack of specificity.
(2) He doubted that our product may hurt the skin.

New actions
Based on the feedback, we borrowed the TurboID technology from BS United China 2022 and replaced last year's AGRD-guided peptide with SP to de-target P. acne to achieve specificity. At the same time, we conducted apoptosis experiments, in which Gpx7 was introduced to perform antioxidant and anti-aging operations on the skin after killing P. acne to achieve the effect of protecting the skin.

Result
We completed the upgrade and successfully enhanced the BS Cleanser.

3.The birth of BS Test kit 2.0 & 3.0, replace the traditional PCR

Feedback
Professor Austin Wu from Columbia University provided us with some document literatures after the meeting, which points us in the direction of upgrading our PCR testing, and exploring more accurate P. acne testing.

Action
We began research on Rolling Circle Replication, ligation, and DNA linkage reactions, and combined all three to design BSDA160 and BSDA360, which were specifically designed to test the skin of P. acne, resulting in the BS Test kit 2.0 (More details are available on the Engineer Success page).

The production phase（September-Now）

Having completed the design of the BS Test kit 2.0 and BS Cleanser, we wanted some feedback from experts and the prospective market.

Action 1
Bloomage BioTechnology Corporation Limited is a well-known biotechnology company and biomaterials company. Driven by synthetic biotechnology, the company is committed to continuously improving the quality of life, extending the length of life, and bringing healthy, beautiful and happy life experiences to human beings. We were honored to meet with company staff who showed us around the R&D center and listened to our introduction of BS Test kit 2.0 and BS cleanser.

Feedback
The company was very interested in our design and gave us a positive opinion, but pointed out that we should make a clear description of the ingredients and a specific description of the use of the product, and said that the research and development department is willing to continue communicating with us.

Fig.9 Visiting the production lines of Bloomage Biotechnology Corporation Limited.

New action
We then asked Mr. Jun from Shanghai International Student Enterprise Association—who has many years of experience in marketing and corporate brand public relations—what he thought about our product. He provided valuable advice on our outer packaging form, cost control, label design, and other issues we had.

Fig.10 Discussion about the packaging of the products with Mr. Jun Wei through remote meeting.

Results
Through this meeting, we completed the production of product samples and outer packaging design and clarified our product ingredients and use methods.

Fig.11 Outer packaging of BS Test kit and BS Cleanser.

Action 2
We communicated with Professor Zhou of Luoyang Central Hospital again, and Professor Zhou gave us some advice.
(1) Our product can show a wider application possibility
(2) SYBR fluorescent protein can be introduced to replace ordinary electrophoresis, making detection faster and more convenient.
(3) Professor Zhou also proposed a new idea for us: we can try to use our method to determine human repeat sequence diseases.

New action
After the meeting, we iteratively upgraded BS Test kit 2.0 and formed the BS Test kit 3.0: Worm L-RCA. See Engineering Success for details. Worm L-RCA is currently applying for a patent jointly with Professor Zhou.