Define the Problem
Staphylococcus aureus, which is a kind of notorious superbug, can beat even the most advanced and powerful antibiotics. According to World Health Organization, lots of people suffer from diseases caused by Staphylococcus aureus, such as Impetigo. This is because medical treatment has improved significantly in recent years, and the use of antibiotic therapy has become quite common, which in turn has led to the development of drug resistance in many bacteria, giving rise to so-called superbugs. In addition, subcutaneous injection is a very direct and effective technique, but it can cause pain and even infection and inflammation in severe cases.
Integrated Human Practice
To address the above issues and clarify the importance of our topic, and ensure that our ideas are more realistic, our team decided to focus on the Integrated Human Practice, asking professors, doctors, experts for their advice, and using their valuable feedback to improve our project.
AMPC Discovery
Dr. Hwan-You Chang
Dr. Hwan-You Chang is a professor at the Institute of Molecular Medicine, National Tsing Hua University, and our Primary PI. With Dr. Chang's many years of experience in microbiological experiments, he helped us to clarify the severity of Staphylococcus aureus and whether our preliminary experimental concept could be carried out.
In each meeting with Dr. Chang, new ideas sparked. For example, we mentioned the concept of Antimicrobial Peptide (AMP) in a meeting with the teacher. After discussion, we suddenly thought of what kind of antimicrobial specificity would be produced if an additional linker was placed in the middle of the AMP, so the concept of AMPC was born. Most importantly, AMPC becomes our best weapon against Staphylococcus aureus. All thanks to the professor's advice.
AMPC Discussion
Dr. Yu-Chun Lin
Dr. Lin is the associate professor in the institution of molecular medicine, National Tsing Hua University. Dr. Lin have extensive knowledge of synthetic biology, and also has been led two terms of NTHU_Taiwan iGEM team to get the golden medal. So we want to learn from his experience and discuss our project with him.
In the beginning, we discuss our topic with him, and Dr. Lin helped us to determine the direction of our project. Moreover, because of his rich experience, we also consulted the medal criteria standards with him. Let us be more purposeful to win the gold medal.
Dr. Chung-Yu Lan
Dr. Chung-Yu Lan is a professor at the Institute of Molecular and Cellular Biology, at National Tsing Hua University. Dr. Lan is a very senior microbiologist. With the guidance of Dr. Chung-Yu Lan, we have made great progress in the experimental technique of gene cloning.
Through the discussion with Dr. Chung-Yu Lan, we improve our technique in transform and cloning, the process of primer design, restriction enzyme cutting site, and purification of a plasmid. At the same time, try adding sequences that have a different primer to plasmic, conducting transform and purification to test.
Dr. Hua-Wen Fu
Dr. Hua-Wen Fu is an associate professor at the Institute of Molecular and Cellular Biology and Department of Life Science, National Tsing-Hua University, who is an expert in protein chemistry.
Dr. Fu gives us much advice about protein chemistry, like which protein-related problems may be encountered in experiments. Through the discussion, we knew how to avoid the situation that unusable protein from the inclusion body, and more detail about gene optimization and purity of the protein. What’s more, If the endotoxin in E.coli and protein sequence we used will affect the human cell, and also the method of preserving AMP.
Senior Che-Kang Chang
Senior Che-Kang Chang is a member of the first NTHU_Taiwan team. He is currently a first-year Ph.D. student in the Biological and Biomedical Sciences Program at the University of North Carolina at Chapel Hill and has previously published papers related to AMP. Therefore, through a discussion in this meeting, we learned the verification method of AMP, such as the necessity of the Minimum Inhibitory Concentration (MIC) test, and the advantages of the Disc diffusion assay. Finally, we also discussed that the Disc diffusion assay is more efficient than the MIC test in a short time which effectively verify the bactericidal effect of our AMPC.
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AMPC Applicator
Dr. I-Chi Lee
Dr.Lee is an Associate professor at the Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, and also our Secondary PI. When we were curious about how to deliver AMPC into the human body, we unconsciously found the technique of painless injection called microneedle, which perfectly fit our requirements.
Fortunately, Dr. Lee has rich knowledge in research of biomaterials including polymeric microneedle technologies. We discussed with her the feasibility of our microneedle project, the method of microneedle patch-making, and how to get microneedle material. After the discussion, we are sure our project, microneedle patch treatment of skin disease is possible.
Win Coat Corporation
Our final goal is to make our products commercialized. So we visited Win Coat Corporation, a company that is professional in the research and development of microneedle materials in Taiwan. The founder of WCC, Dr. Ta-Jo Liu, served as a senior research scientist at Kodak (USA) Co. before, he was also a professor and chairman at the Chemical Engineering Department of National Tsing Hua University. Dr. Liu has rich knowledge about the marketing and materials selection experience of the microneedle.
Dr. Liu provided us with some key points about how to commercialize the new microneedle we’ve made, the experience of their marketing skills, and also the difficulties they’ve overcome. Then, Dr. Liu also took us to visit the professional microneedle production equipment of Win Coat Corporation, which was impressive.
The purpose of our Project is to increase the convenience of treating skin diseases for the general public. To ensure that our project has the possibility of becoming a convenient commodity in the future, we got the following suggestions from Dr. Liu:
- Attention and selection of microneedle materials used in the medical field
- Patents, promotion, cost control, and future market demand of microneedle.
- The pyramid-shaped microneedle will greatly increase the success of puncturing the skin.
- Materials and design for microneedle packaging.
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AMPC Release Prediction
Dr. Lee-Wei Yang
Dr. Yang is a professor at the Institute of Bioinformatics and Structural Biology, at National Tsing Hua University. Dr. Yang gave us advice about bioinformatics and structure. We have received many suggestions on protein sequence modeling from Dr. Lee-Wei Yang.
Through the discussion with Dr. Yang, we knew the ConSurf sequence alignment and the proper use of Classical Molecular Dynamics Simulations and gave us the concept that if multiple AMP structure changes, the activity of AMP complex may change a lot. After the discussion, we change the orientation of dry lab because we realized that the chemical bond simulation is too difficult for us. So, we turn to the simulation of the junction.
Project Feasibility
Dr. Chun-Yi Lin
After having professional advice, we are eager to understand more real clinical cases that will happen in our real life. Therefore, we interviewed Dr. Lin.
Dr. Chun-Yi Lin is a Pediatrician at Lin Chun Yi Pediatric Specialist Clinic and also a pediatric expert with more than ten years of experience in treating skin infections. With Dr. Lin's rich experience in pediatrics, we believed she can help us definitely to clarify the needs of children for microneedle platforms, as well as relevant clinical suggestions.
After the interview, Dr.Lin suggested that Furuncles or Carbuncles are the severe diseases caused by S. aureus, which are more suitable for our novel design, so we modify our project’s direction. Furthermore, we should try to apply the microneedle as an alternative to drug-loading.
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Alumni Association
Every year, the College of Life Science of NTHU holds an alumni association, inviting alumni to go back to the school to participate in the reunion, and our team took this opportunity to share our project with several of the alumni. Some alumni are researchers, professors, and even the chairman of the company. So we got advice from academia, business, and more to help us think from a different perspective.
Sustainable
See Sustainable page for detail information.
Project Safety
Dr. Chien Chung
Dr. Chung is an emeritus professor in the Department of Biomedical Engineering and Environmental Sciences, at National Tsing Hua University and also our Secondary PI.
Dr. Chung is an expert in biosafety. Through Dr. Chung's advice, we have never had any danger or accident during our biological experiments. Also, through the discussion with Dr. Chung, we earned more detail about intellectual property rights, such as application, qualifications, and necessity, and also gave us some suggestions about team management.
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