Integrated Human Practices

Integrated human practices is one of the most important parts in our project every year, which gives us an opportunity to communicate with the experienced, modifying our decision. After the outbreak period of Covid-19, we cherish the offline communication opportunities of this year's project more than ever.

This year, our team has enhanced the integrated human practices methodology "problem-solution" loop created by 2020 UCAS-China through further refining it as the "problem - solution -reflection" loop. This approach involves seeking answers with certain questions, then reaching for experts to solve, and finally reflecting on how we improve ourselves more than only solving one question.

Let’s see how this loop direct us throughout the project.

For background and marketing considerations, please click "implementation" page to check how our project connect with society.

Professor Keng-Chang Tsai

National Research Institute of Chinese Medicine, Taiwan

Problem: Despite extensive research on nanobodies in the early stages, there is still uncertainty regarding the specific considerations involved in the design process. We aim to engage in discussions with professionals from relevant fields.

Conversation with Prof. Tsai: Upon discovering a relevant article, we reached out to Professor Tsai, the first author, via email seeking assistance.

Conversation with Prof. Tsai

Solution: It is crucial to ensure that the fusion protein can be correctly folded within the bacterial expression system. Incorporating flexible linkers between the domains may be necessary to ensure independent folding. Additionally, it is important to monitor and address potential toxicity or stress on E. coli resulting from the expression of the synthetic receptor.

Reflection: Prof. Tsai's response has provided us with valuable insights for nanobody construction. During our review of relevant literature, we will emphasize these considerations and make necessary improvements, particularly in significant areas such as linkers.

Beijing Hotgen Biotech

Problem: Thus far, our project aims to detect micro molecules. Is our approach feasible? We have encountered several questions during the detection process, such as determining the limit of detection (LOD) for home-based detection devices and identifying key considerations for designing a detection device. We came across Beijing Hotgen Biotech, a company specializing in the design of detection instruments.

Meeting with Hotgen Biotech

Conversation with Beijing Hotgen Biotech: We engaged in discussions with the experts at Hotgen Biology regarding the specific challenges along our pathway. These included determining the optimal time for quorum sensing system detection, considering the influence of AHL and solvents on bacterial growth, and evaluating the impact of detected substances on bacteria. We also addressed hardware aspects, substance state detection, and modeling.

Picture after meeting

Solution: The samples to be tested can undergo pre-processing to minimize their impact on bacteria. Additionally, we propose employing a visually-based reporting method as the final signal output, eliminating the reliance on large instruments. This approach enables low-cost and home-based detection of small molecules.

Reflection: During the experiment, it is crucial to fully consider the impact of added substances on bacterial growth. If the substance being tested is toxic to the bacteria, the fluorescence intensity-concentration curve may follow a parabolic pattern. Similar issues must be thoroughly considered throughout the experiment. Ultimately, visual luciferase is utilized for signal output.

Professor Pingsheng Liu

Institution of Biophysics, CAS, who expertise in Lipid droplet biology

Problem: The blood of healthy people and patients with liver damage also contains bile acid. This is because bile acid secreted by the liver is reabsorbed by the small intestine and enters the blood. How to judge whether the bile acid detected is released due to rupture of liver cells or exoccreted by the liver and reabsorbed by the small intestine?

Conversation with Prof. Liu: We visited Prof. Liu’s office to get his advice.

With prof. Liu

Solution: Bile acid is divided into many types based on different side chains. Bile acid secreted by the liver will be modified by certain bacteria in the intestinal flora and then reabsorbed by the small intestine. The side chains of these modified bile acids are different from the unmodified bile acids in liver cells. If the nanobody can specifically bind to unmodified cholic acid, specific effects can be achieved.

Reflection: We pay special attention to the binding specificity of nanobodies and bile acids during the design process.

Professor Changqing Zeng

Beijing Institute of Genomics, CAS, specializing in Bioethics

Problem: While most E. coli strains are non-pathogenic, certain serotypes can pose risks to humans and animals. If these pathogenic E. coli strains are utilized in experiments or subjected to genetic modification, biosafety concerns may arise.

Conversation with Prof. Zeng: We visited Prof. Zeng's office to seek her advice.

Solution: When employing E. coli for genetic engineering purposes, it is essential to adhere to relevant national and local regulations and standards. Additionally, stringent protective measures should be implemented to prevent E. coli leakage or contamination. Moreover, we must consciously uphold ethical norms, ensuring that the experimental objectives, methods, and conditions align with ethical principles and social responsibilities.

Reflection: During experiments, it is crucial to carefully screen and exclusively utilize non-pathogenic strains of E. coli. Furthermore, robust protective measures should be employed to prevent any potential leakage or contamination of E. coli.

Doctor Cang Wang

CAS Delta Capital

Problem: During the implementation write-up, we summarized the market demands, advantages, and risks related to NOX. We believe that NOX can carve out a niche in the application market due to its high detection specificity, compact size, and low cost. However, due to our limited understanding of technology transfer, we sought guidance from professionals to assess if our approach is on the right track. As a result, we contacted Dr. Wang, a specialist in technology transfer at CAS Delta Capital, with expertise in bioengineering, for consultation.

CAS Delta Capital logo

Conversation with Dr. Wang: We reached out to Dr. Wang over the phone to seek his advice.

Solution: Dr. Wang pointed out succinctly that the most crucial aspect of our product, as a detection instrument in synthetic biology applications, is its ability to provide products at low cost, in large quantities, and with consistency. For biological products to meet the requirements of industrial standards for uniform quality, we need to consider the possibility of mutations. Additionally, Dr. Wang made corrections and suggestions regarding our approach. He emphasized the importance of conducting research aligned with the needs of the target audience. The public is more concerned about the demand for detecting specific small molecules rather than the introduction of a single instrument. This approach will attract more attention in the market.

Reflection:

We improved the write-up of the market research in the implementation section and reassessed the safety risks associated with the product.
We realized the importance of starting from the foundational level to build our project. This mindset continued to guide our entire team, making our project more logical.
Understand why the public would need our project and identify the target audience.
Assess the ability to produce the product in large quantities with consistency. While chemical and semi-chemical processes have achieved significant advancements in terms of scalability and consistency, biological systems inherently carry the risk of mutations, which can lead to inconsistencies.
Determine the extent of the price advantage offered by the product. Market size calculations are necessary to assess the potential pricing advantage.
Design overall and hardware user manual. We realized that the ultimate end users of our product are people in daily life, so we have designed a overall and hardware user manual to guide them on how to use our product and how to use it safely (see description and hardware)

After Judging Session

After communicating with our judges in the judging session and getting feedback, we realized that there are several aspects we should consider in follow-up:

Apart from directly providing for personal use, companies that have the resources to handle the systematic difficulty of SynBio products are also worth deliberate thoughts.
We should place more focus on biosecurity and how to dispose of our product safely at home and refine the user manual accordingly.
We need more scientific data to support our understanding of the issues related to BPA and bile salt testing. We need to rely on more scientific evidence in our background research and clarify the disvantages of current approaches.
Our hardware lacks consideration for user feedback. We should seek individuals without a scientific background to engage in hardware usage or read our manual, integrating their feedback into the design of our hardware.

We are extremely grateful for all the advice and will be continuously improving NOX afterwards.