OVERVIEW
Figure 1: The whole process of intergrated human practice
In order to make our project a feasible, novel treatment for acne, we did many consultations and researches.
The work we did could be mainly divided into theoretical part and practical part. In the theoretical part, we:
consulted specialists in different fields during design process.
interviewed dermatologists from whom we were told the most feasible way to cure acne.
We hope our project will not only be a design, but also can be produced. To achieve this goal, we:
visited pharmacies to investigate the sales of acne drugs.
distributed questionnaire, we received more than 200 results, which reflect public's perception of acne.
visited companies. Professionals from companies told us what we should do for the realization of our design.
For the further survey, we also plan to write a business plan and interview patients.
From our human practice, we finished the design, and primarily explored the way to bring our design to reality. In the human practice we did throughout the competition period, all the people we contacted inspired us, and gave us confidence to continued our work.
INITIAL STAGE: FEASIBILITY
CONSULTATION WITH YI ZHAN:
SYNTHETIC BIOLOGY METHODS AND PROTOCOLS
Since this is the first time for our team to participate in the iGEM competition, we consulted Dr. Zhan, who is an experienced mentor of iGEM and in charge of studies and research at college of life science and technology in HUST. During the meeting, we introduced the expectations of our project and the experimental scheme we had designed. Dr. Zhan suggested us to make our design goal-oriented, and make it a top-down design. He also suggested us to strengthen the connection between parts, and encouraged us to imagine boldly.
Throughout the competition, we regularly communicate our experimental progress with him. He gave us much guidance in how to carry out experiment in limited time.
Figure 2: Yi Zhan, counselor from college of life science and technology in HUST
ASSOCIATE RESEARCH FELLOW HU:
TEMPERATURE CONTROLLED EXPRESSION SYSTEM
Associate research fellow Jun Hu has worked a lot with nanomedicine and nanoparticles. In the early days of our project, he attended almost every discussion we had and gave us a lot of practical advice on the project, especially on the design of the expression system. As we hope to use a nontoxic and handy method to produce our protein, we find it could be easily work out by sensitive promoting protein expression. After times of communication, we finally decided to enable light induction to achieve efficient protein expression. And Dr. Hu recommended us to use pL/pR promoter in our expression system, to achieve building an intelligent personalized practical system , Nano-AI-Cleaner.
He also mentioned that after the bacteria death, the acylated protein would still exist, which can introduce TLR2-mediated immune response, leading to acne lesion. Therefore, we began to thinking about how to solve the inflammation.
Figure 3: Jun Hu, associate research fellow from HUST, mainly engaged in nanomedicine
Figure 4: Consultations with expert
CONSULTATION WITH PROFESSOR WEI LIU:
ANTIBACTERIAL AND ANTI-INFLAMMATORY EFFECT
We reached out to Prof. Liu, an expert in nanotechnology and cosmetics developing, who has also dabbled in the development of acne treatment products, to obtain some inspirations from him.
At the beginning, our project was only pointed at one target of P. acnes. But with the depth of mining and through the consultation with Prof. Liu, we saw that the pathogenic mechanism of acne is very complex, thus current effective treatments were meant to be multi-target, and we started to consider improving our project to have multiple function. So we rearranged the original project design and decided to use one of the solutions, namely to design TLR2 antagonist. This modification allows the product to function as both antibacterial and anti-inflammatory agents.
Figure 5: Wei Liu, professor from HUST, mainly engaged in nanotechnology
ASSOCIATE PROFESSOR. WANG SHENG: MODELING DESIGN
Associate professor Sheng Wang is a specialist in protein structure and computational biology, and he inspirits us to develop the TLR2 antagonist through a rational structure-based approach. Dr. Wang gave us a lot of useful advice and help on designing TLR2 antagonists and screening for a stable binding agent by teaching us to calculate the stability of TLR2, which meant a lot to us at the initial stage, and laid a solid foundation to our further progress. Additionally, In the experimental stage, he provided us with many valuable suggestions and support on how to purify our target protein, which brings our project reality to one step closer.
Figure 6: Sheng Wang, associate professor from HUST, mainly engaged in protein structure and computational biology
MEDIUM STAGE: ADVANTAGES AND DISADVANTAGES
BACKGROUND
During the progress of our project, we came to the situation that we need more information of epidemiology related to acne and clinical treatment. Thus, we interviewed dermatologists to get advice to make our project more effective and meet the requirement of clinical application.
DOCTOR YAMIN ZHANG
We interviewed Dr. Zhang, a dermatologist at Tongji Hospital affiliated to Huazhong University of Science and Technology in Wuhan.
After we introduced our program to Dr. Zhang, Dr. Zhang spoke highly of our project, and she made some suggestions for our project. In addition, Dr. Zhang mentioned that there are already microbium-containing cosmetics on the market, which gives us great confidence to improve and expand our program.
According to Dr. Zhang 's introduction, acne is one of the most prevalent skin diseases in the world at present, and has adverse effects on the confidence, appearance, mental health and even finances of patients as well as their families. At the same time, acne is complex in its pathophysiology and can be difficult to cure. In the interview, Dr. Zhang introduced the stages of acne and the drugs used correspondingly. We have defined the product positioning of our project according to the stage classification, which should be used in the inflammatory papule and later stage to achieve the best results.
Figure 7: Dr. Zhang introducing acne clinical guideline to us
DOCTOR XIAOHAN LU
We also got in touch with Dr. Lu, deputy Director of the Yingde chronic disease prevention and treatment hospital. Dr. Lu has a lot of experience in acne treatment, so we mainly asked him some questions about the epidemiology of acne.
According to Dr. Lus words, severe acne, such as nodules and cysts, will leave scars after healing, and the treatment of these scars may be a huge amount of consumption, which makes many patients bear mental and economic pressure. In Dr. Lu 's diagnosis and treatment experience, adolescent males suffered most among all patients aged 10 to 30. This information has greatly raised our awareness on adolescences mental health, inspiring us to implement our subsequent human practice and experiment.
At last, Dr. Lu also told us about his clinical experience in recent years: with the development of society, the improvement of people's living standards, more and more people are paying attention to skin diseases, which is an important part of the increasing number of patients to the dermatology treatment. This made us realize that our project has grant potential demands in public and future society, giving us more courage to carry on our project.
Figure 8: Online interview with Dr. Lu
LATER STAGE: DEVELOPMENT
PHARMACIES:
SALES AND MARKET RESEARCH OF ACNE DRUGS
After knowing the types and names of commonly used acne drugs from doctors, we went on to the next work: we visited several pharmacies to learn about the sales of acne drugs, such as the age and gender of the buyer, since we believe that learning the buyer's profile will help us make well-directed improvements to our products based on personas.
We learned from the pharmacies that the age of patients who buy acne drugs is basically 20-30 years old, and there are slightly more men than women. This is mostly in line with the information we get from doctors.
We also raised some questions related to biological treatment protocols, such as the staffs acquaintance with biological treatment protocols. The results of the interview showed that: (1) the staff of all pharmacies did not recognize the biological treatment protocols; (2) The most popular microbial products are intestinal probiotics.
This result shows that the biological treatment protocols has not come to the public, but some products have been already accepted by the public before the coming of biological treatment protocols. We believe that this is inseparable from the research and vigorous publicity of intestinal microorganisms in recent years. At the same time, this also makes us think about whether the research on skin microorganisms will bring our products, biological acne treatment products, to the public's view in the future? We trust that the answer to this question is certain.
Figure 9: Team members visiting China Associate Pharmacy
Figure 10: Team members visiting Bailitang Pharmacy
Figure 11: Research data of pharmacies visiting
QUESTIONNAIRE: PUBLICS PERCEPTION OF ACNE
To have a better understanding of people's knowledge of acne, we issued a questionnaire and obtained 271 samples. We noticed that the morbidity for male is a little higher than that of female
Figure 12: statistical data of question: have you suffered from acne?
Following are some important questions of all.
What's your age?
Figure 13: statistical data of question: What's your age?
Which options below do you know about acne?
Figure 14: statistical data of question: Which options below do you know about acne?
The therapy you once used
Figure 15: statistical data of question: The therapy you once used
We plan to develop a multifunctional nano-ball which combine antimicrobial peptide and TLR2 antagonist to realize sterilization and anti-inflammation. Whats your expectation of our Project?
Figure 16: statistical data of question:Whats your expectation of our Project?
The statistics showed us the most important basic information of acne in China including the distribution of acne patients by sex and age, people's knowledge of acne, people's degree of acne, current therapies mostly applied, people's comment on current therapies, the defect of current therapies and people's expectation for new therapies. Based on these basic information, we could respectively decide the goal we hope to attain and what improvement we can try to achieve.
VISITING ENTERPRISES:
DEVELOPMENT STATUS AND MARKET STATUS
ASCENTAGE PHARMA: APPLICATION SCENARIOS
We had an meeting with Dajun Yang, the CEO of Ascentage Pharma, which is a listed pharmaceutical company. After we introduced the project design and current progress, Mr. Yang asked us several questions and put forward some suggestions to us.
First of all, Mr. Yang gave us positive appraisal on our experimental design and the yield of protein 5-10mg / L bacterial solution. Later, knowing that protein is an essential parts of our products, Mr. Yang asked about the stability of protein and suggested that we set some special temperatures, such as room temperature, to verify the stability of protein. Secondly, Mr. Yang also asked questions about our product development, for instance, He asked about whether our protein had been applied in the field of acne treatment, and whether we acquainted the development status of acne related pharmaceutical products in China. Finally, he specially reminded us that we need to clarify the application scenarios and positioning of our products.
After this online meeting with Mr. Yang, we gained a grand-new perspective on pharmaceutical product development to rethink our NANO-AI-Cleaner system. Although antimicrobial peptides, one of our two main proteins, is also a new research topic, their application in the treatment of acne has not been reported. Therefore, our application of antimicrobial peptides in the treatment of acne is very novel. Besides, reminded by Mr. Yang, we also reconsidered the application scenario and product positioning of our products.
Figure 17: Online interview with ascentage pharma
Figure 18: Dajun Yang, CEO of ascentage pharma
BESTCARE-BIO: PRODUCT FORM
We communicated with the professional technicians of BestCare-Bio, a biotechnology company and professional cosmetics company. BestCare-Bio staff gave us more advice on our product details.
Firstly, BestCare-Bio members remind us that the presence of live bacteria in cosmetics is not allowed under the current cosmetics legal framework, so it is more practical for us to consider other product forms, like the use of inactivated bacteria, but we are supposed to ensure the existence of active constituents.
Secondly, although we had a preliminary conception about the application scenario of our products from the experience of our previous visit at Ascentage Pharma, BestCare-Bio staff also emphasized except from considering the proper application scenario, hospitals, beauty salons or families, we should also take two points into account what stage of treatment is our project aimed at and how long does our medicine work. Besides, BestCare-Bio staff also advise us to consider various forms of the product, like hydrogels.
Figure 19: Group photo of our team member and staff from BestCare-Bio
BEST CARRIER: MODEL OF PRODUCT
Best Carrier is also a specialized cosmetics development company. They offered us beneficial tips on the induced expression methods of our products and the process of experiment.
As for the induced expression methods of our products, the professionals of Best Carrier pointed out some problems in our project. For example, the utility of the products will be uncontrollable with the change of the environment and the step of use of our mask is slightly cumbersome because it involves infrared radiation and Specific application temperature.
After the personnel of Best Carrier had listened to the current progress of our experiment, they note that for our products, the most important thing now is to prove its effectiveness, and we should give priority to completing our function verification experiments. In addition, they also suggeste that we make further quantitative experiments to determine whether the protein produced by our system can achieve the expected effect. Finally, they advise us to conduct controlled experiments with existing peptide products on the market to illustrate the effectiveness of our products. These valuable opinions make us decide to adjust our experiment process and guide our follow-up experiments.
Figure 20: Group photo of our team member and staff from Best Carrier
FURTHER SURVEY: TO THE PUBLIC
BUSINESS PLAN: INDUSTRY STATUS, OUR POSSIBILITIES
In the middle stage of our project, we have completed an investigation report to make our products better meet market demand. In the report, we summarized the existing acne treatment products on the market, but for various reasons, we havent accomplished the comparation and analyzation of the acne products with beauty products for acne treating as planned. In the follow-up work, we propose to complete this report. And we will compare our products with current products to analyze its advantages and weakness.
Moreover, we also plan to take the information provided in this survey report as the background to prepare our products for further popularization. We will write a business plan for our product and analyze the opportunities and challenges it will face in the market.
PATIENT INTERVIEW: SOCIAL ACCEPTANCE
Because of the limited time, we can't finish more work before the competition, but our human practice activities will not stop here.
From the work we have completed, we know that there are some regulatory obstacles for our products coming to the real world. Therefore, we want to do a fieldwork for acne patients and people from all walks of life to comprehend whether our products can be accepted by the public and what is the degree of acceptance.
This survey will not only contribute to the promotion of our products, but also help us consider: with the development of science and the increase of public acceptance, is it possible to change current laws and regulations on pharmaceutical products or cosmetics to meet more novel things?