Scientific research aims to make a meaningful impact on human society. It’s necessary to understand the industrial demand and tackle problems in the real world. Integrated Human Practices helps us avoid isolated works. We continuously consult different people from academia and industry in every important step of our project.
Methodology
Integrated Human Practices consist of three important steps:
Idea formulation
Project design and optimization
Further extension and application
Here is our timeline of Integrated Human Practices
The main approach we used is the interview. During the conversation, we focus on three main questions:
Is our idea of this project reasonable and does it have practical significance?
What can we do for improvement?
How can we develop a plan for an extension?
In the following contents, “Drug” indicates the small-molecule inhibitor against some specific bacteriophage we got via virtual screening.
Phase A
A Interview Dr. Liang Yang, Professor in Medical Microbiology - The “naïve thinking”
Last year, the SUSTech_Shenzhen team designed a biobrick for cytotherapy. We started our brainstorming in a therapeutic situation. So, we firstly interviewed Dr. Liang Yang from the School of Medicine.
He introduced the clinical demands about fighting against Pseudomonas Aeruginosa, which was a significant pathogen in nosocomial infections as well as chronic obstructive pulmonary diseases (COPD).
We then came up with an idea about bacteriophage therapy: It’s promising to modify bacteriophage and biobrick for controlling the invasion of Pseudomonas Aeruginosa, to avoid antibiotic resistance.
Interviewed with Dr. Liang Yang
We then started our project design. While searching for the target protein, we found it was interesting that the bacteriophage could develop an anti-CRISPR system to counteract the CRISPR system in bacteria. We started focusing on Aca1 protein expressed in some specific bacteriophages1 which can invade Pseudomonas under the guidance of Dr. Hongda Huang.
Dr. Liang Yang
Professor
Medical Microbiology
School of Medicine, SUSTech
Phase B
Interview Mr. Shengchun Wu, Vice Manager at Shenzhen Techand Ecological and Environmental Co. Ltd. - Understand the microbial community in sewage treatment and Determine to choose Pseudomonas
We searched for suggestions about Pseudomonas from different relative fields, including synthetic biology, chemical biology, environmental engineering, and medicine.
Initially, we tried to inhibit the growth of bacteriophage via virtual-screening molecule to protect Pseudomonas, because Pseudomonasplays a significant role in sewage treatment.
However, Shengchun Wu told us that instead of avoiding the invasion of bacteriophage, they utilized bacteriophage to control the dynamic equilibrium of bacteria in the waste-processing system.
We found that in their industry, they integrated multiple species of bacteria in the activated sludge to construct a system of bioremediation, rather than only using Pseudomonas.
Based on his suggestions, we looked deeper into biofilm in sewage treatment and understood the complicated components of the microbial community, including Acinetobacter, Aeromonas, Pseudomonas2, and many other microbes. But it’s still possible to find the “Drug” to protect Pseudomonas from excessive phage infection is viable in finding molecules responsible for other microbes in the complex community of biofilm.
Online-discussion with Mr. Shengchun Wu
Mr. Shengchun Wu
Environmental Engineering
VP
Shenzhen Techand Ecological and Environmental Co. Ltd.
Phase C
Interview Dr. Kai Jiang, Research Associate Professor in Chemical Biology
We consulted Dr. Kai Jiang about chemical genetic approaches to screen our Drug and the possible application of the two-plasmid report system.
As a chemical biologist, he appreciated this system and he brought up that it was suitable to achieve high throughput screening via 384-well assay plates.
He also suggested that we can try to utilize certain prepared chemical banks that contain bioactive chemicals with known in vivo targets or even approved drugs. This strategy would certainly be more efficient than screening over a random chemical bank. and we integrated his advice into our further plan.
After communicating with Dr. Kai Jiang, we enjoyed granadilla together with him
Dr. Kai Jiang
Research Associate Professor
Chemical Genetics
Academy for Advanced and Interdisciplinary Studies, SUSTech
Phase D
Interview Dr. Yinfei Ma, Researcher in Synthetic Biology
We communicated Dr. Yingfei Ma with the anti-CRISPR system and how to optimize the two-plasmid report system.
As a synthetic biologist, Dr. Yingfei Ma guided us to analyze different bacteriophages which can be used for testing.
He was not sure if they got phages code Aca1 protein, but he was willing to look it up.
He suggested that we might edit an E. coli phage if we were not able to find the phage we wanted.
Using the edited E. coli phage, we could also “directly” test the efficiency of our drug.
Discuss more details about our project with a PhD student in Dr. Yingfei Ma’s Lab
Dr. Yinfei Ma
Professor, Principal Investigator
Synthetic Microbiome
Center of Synthetic Microbiome, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences
Phase E
Interview Dr. Liang Yang, Professor, School of Medicine, SUSTech
We then interviewed Dr. Liang Yang again. As a specialist in molecular microbiology, he gave us lots of reasonable suggestions about our project：
How to optimize our experiment, how to design tests to verify the efficiency of our drug.
He also talked about two tricky problems with bacteriophage.
The first one is that, in the microbiology and structural biology lab, invasion of bacteriophage is common and easily lead to a catastrophe in the pure culture of bacteria. If the drug can be added to the medium, it is able to inhibit the invasion of bacteriophage. It’s similar that, in the biosynthesis and biodegradation industry, like vitamin B12 biosynthesis, such drugs can protect Pseudomonas from the invasion of phage in massive cultivation.
For another, he mentioned the application of biofilm in sewage treatment. Commonly, environmental companies prefer to inoculate biofilm into a series of tubes for degrading polluted water. The over-proliferation of biofilm may block the tubes and now the environmental companies can only change for new ones.
Therefore, if we can utilize the drug to construct a system that can monitor the demand of bacteriophage and then adjust the quantity of biofilm, it may improve the efficiency of environmental companies and help to tackle the environmental problems. We developed a future plan according to his suggestions and tried to discover a proper molecule with a broad-spectrum application based on the existed project.
Photo in Dr. Liang Yang ’s lab
References
Stanley, S. Y., et al. Anti-CRISPR-Associated Proteins Are Crucial Repressors of Anti-CRISPR Transcription. Cell178, 1452-1464.e1413, doi:https://doi.org/10.1016/j.cell.2019.07.046 (2019).
Kämpfer, P. et al. Characterization of bacterial communities from activated sludge: Culture-dependent numerical identification versus in situ identification using group- and genus-specific rRNA-targeted oligonucleotide probes. Microbial Ecology32, 101-121, doi:10.1007/BF00185883 (1996).
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