Human practices

Expertise and Background:
Dr. Muto specializes in bioinformatics. He uses bioinformatics methods to conduct comparative genomics of anaerobic bacteria and molecular evolutionary analysis. His research focuses on understanding drug resistance and host symbiosis mechanisms. He is also studying the biological functions of sphingolipids possessed by resident anaerobic bacteria in the intestines and their relationship with the host (humans).
Link to Dr. Muto's profile

Insights Gained:

• Discussed the process of gathering DNA using pamconaligner.
• Received advice that creating a phylogenetic tree from the sequence we want to knock out and nearby DNA would be efficient.
• Learned about NCBI operations and Linux operations from Dr. Muto.

Expertise:
Dr. Ando is a specialist in phage therapy. He is part of the Next-Generation Phage Therapy Research Unit established in 2020. Their aim is to develop therapeutic methods using artificial bacteriophages that overcome the challenges of natural phages. Dr. Ando, with his high expertise, leads the Gifu University Phage Biologics Research Lecture. They are actively promoting open innovation to deliver new treatments to patients suffering from refractory bacterial infections and microbiome-related diseases as soon as possible.
Link to Dr. Ando's phage therapy research

Insights Gained:

• Learned about different types of phages and about phagemids as vectors.
• Discussed our seed technology's transmission method, specifically the idea of inserting the plasmid of cas9 into the head of the phage to deliver it to bacteria.
• Understood that without a tangible phage medicine, discussions about its potential won't take place. There is currently no phage medicine available.
• Realized the necessity of a novel method to deliver medicine into the body, equivalent or superior to current treatments, to actualize treatments other than antibiotics.
• Concluded that delivering our designed gRNA, which recognizes similar sequences with cas9, into the body is not feasible within the current competition.

We had the privilege of presenting our research to Dr. Hisashi Baba of the Infection Control Department at Gifu University Hospital's Biomedical Support Center, receiving valuable guidance. Among the advice we received, we would like to highlight three key insights that significantly influenced the direction of our research activities.

First and foremost, it was emphasized that infection prevention and treatment are distinct entities. While this may seem obvious, it is not always the norm in Japan, where hospitals and other institutions often lack clear separation between these two areas. However, internationally, these aspects are typically considered separately. Therefore, when presenting research abroad, it is essential to clarify whether the focus is on infection prevention or treatment.

The second insight underscores the importance of using terminology relevant to the chosen research theme and field. For instance, as our research falls within the field of phage therapy, we were advised that the term "treatment resistance" is more appropriate than "drug resistance." Even seemingly similar terms can carry distinct meanings, and using them interchangeably can raise doubts about the relevance of the research.
The third insight highlighted the need for technology that can promptly address emerging mutant strains, which are anticipated to appear in the future. While there are currently antibiotics capable of combating bacteria with a wide range of treatment-resistant genes, phage therapy is considered essential for countering novel threats, such as future mutant strains similar to the emergence of the COVID-19 virus.
Taking this advice into consideration, we made significant changes to our research direction. Initially, our research had an ambiguous goal, targeting both "prevention" and "cure." Furthermore, we were primarily concentrated on achieving "broad efficacy in existing mutant strains." However, following valuable advice, we refocused our efforts solely on finding a "cure." Additionally, we decided to shift our research emphasis from addressing only existing mutant strains to proactively preparing for future threats.
In summary, Dr. Baba's opinion transformed our research. We felt that there is a big difference between the ideas and issues in research and in the field of treatment. We also felt that in order to implement our tool, "Variant Guard," we had to reflect the opinions of stakeholders such as physicians and pharmacists in the medical field in our research to be sure.
Link to Dr. Baba's profile

Understanding the Field

As part of our iGEM Human Practices activities, we had the privilege of hearing valuable insights from Dr. Akio Suzuki, the head of the Pharmacy Department at Gifu University Hospital (click here), as well as Dr. Takashi Niwa from the Infection Control Team and the Antimicrobial Stewardship Support Team.

Through the discussions with Dr. Suzuki and Dr. Niwa, we gained a profound understanding that antibiotic therapy is often viewed as a "short-term battle." This perspective emphasizes aiming for a long-term symbiotic relationship with microbes, even when treating infections without antibiotics. Moreover, we learned about the current shortage of potential candidates for new antibiotics.

Of particular note is the existence of variants of Staphylococcus aureus that carry a gene for secreting coagulase into the bloodstream. These variants are known to be extremely challenging to treat with antibiotics. Dr. Niwa proposed an intriguing idea, suggesting that our Gifu team's developed "variant gard" might be effective in treating such mutants. Leveraging this valuable feedback, we have decided to proceed with experiments targeting coagulase in Staphylococcus aureus during the dry engineering and modeling stages.