Team:SCU-China/Consultation/Prof

HUMAN PRACTICE

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CONSULTING WITH PROFESSOR

Prof. Wang Chengshu

At the very beginning of 2019 SCU-China's project this year, we were very lucky to get connected with the discoverer of cordycepin in Cordyceps militaris, professor Wang Chengshu in the Shanghai Institute of Plant Physiology and Ecology. The members of SCU-China communicated with professor Wang with several questions about the production of cordycepin in yeast. At last, we got two important messages as below:

1. the function of the NK domain of Cns3 is unclear.
2. the expression of Cns3 in yeast is unclear.

So, based on the information we get from professor Wang, we decided to study more about the HisG domain of Cns3 instead of NK. Another reason for giving up NK domain is that the product catalyzed by NK domain can be got from RNA degraded.

Prof. ke Liu

We used Saccharomyces cerevisiae AH109 as our chassis to construct Met/Gal4 delay expression system initially. But we couldn’t get a desirable moon colony in SD-Ura plate. Considering Professor Liu is a specialist in yeast, we consulted him for some guidance.

After talking with Professor Liu, we knew that AH109 contains the Ura gene. This gene stopped us from screening yeast in the SD-Ura plate and made yeast congregated. He advised us to choose other kinds of yeast for screening in SD-Ura plate.

Thus, we referred to the internet for information and finally determined to use S.cerevisiae YM4271.

There are several advantages to use S.cerevisiae YM4271. First, it’s available to get a moon colony in SD-Ura plate. Second, it’s Gal4 and Gal80 gene defect. Third, it’s self-sufficient in Met. All of those merits mentioned above are perfectly suitable for the Met/Gal delay expression system.

In a word, guidance from Professor Liu corrected our experiment plan in time and prevented our efforts from being in vain. We all appreciate Professor Liu’s help.

Prof. Yang Cao

Prof. Cao Yang is an expert in computational structural biology in our school, who used to finish his doctorate in protein structure prediction and molecular kinetics at the University of Michigan.

In the situation of being blocked by the poor structure prediction result of the enzymes by homology modeling, we turned to Prof. Cao Yang for help. He listed the weakness of the utility of homology modeling, relying heavily on the coverage and quality of the template structure. If our querying proteins have some homogeneous counterparts which are well characterized and analyzed, this kind of method is efficient and sufficient. However, if not, it is inappropriate to use homology modeling. He recommended another type of structure prediction methods, called fold recognition, which has another alias, protein threading. This method is more suitable in our case as we can not find proper templates.

When we conducted our molecular kinetic simulation, Prof. Cao gave us support for the Linux environment and the software package, GROMACS, running on it.

Prof. Jing Huang

Professor Huang Jing is a specialist in the field of natural medicine and is currently working in the department of Natural Medicine, West China Pharmaceutical College, Sichuan University. His contributions include active ingredient study of Ilexlatifolia, an exploratory study of H-NMR for the analysis of metabolism in animals with Traditional Chinese Medicine (TCM) prescription, the study on extraction and purification of LNT, and some researches on several generic TCM.

For now, Prof. Huang engaged in the study of bioactive components of natural drugs (TCM) and NMR analysis of absorption and metabolism of natural medicine in vivo.

We decided to interview him to discuss some of our questions. That's because: 1. Our topic is related to cordycepin, which itself is a kind of TCM with a long history, and it is a natural medicine as well. 2. We believe that Prof. Huang has active academic thinking, and he has proved his rich knowledge and experience. 3. Prof. Huang is making products relevant to sweet-scented osmanthus, which has already been on the market and has an estimated market value of hundreds of millions. So he is a good example combining scientific research and industrialization that of great value for reference.

During our interview with him, we wanted to learn how TCM impacts our health and whether it is meaningful for us to focus on Cordyceps militaris and COR. He helped identify some of the key bottlenecks in the application of COR and TCM; although scientists have been working on COR since the 1950s, there are relatively few commercial tests available despite advances in research. He chalked this up to stringent regulatory oversight as well as some technical limitations. Although TCM regards cordyceps as effective medicinal herbs, the active ingredient and mechanism of its action are still unknown. What's more, TCM is a complex mixture hence it's hard for researchers to affirm which ingredient is effective. And the traditional method to produce COR isn't satisfactory. For that reason, he told us that the key to taking advantage of TCM is trying to reduce the number of mixed herbs in the prescription. And our working has not only a potential market but also advantages in industrial production, which is meaningful.

After talking with Prof. Huang, we reaffirmed that our project was going to function in the application (main production) of traditional medicine and the optimization of the synthesis of COR. We also realized that it is one of the most significant challenges for us to revive TCM and we hope the optimization of the synthesis of COR will help TCM out of its dilemma.

Prof. Lili Wang

In order to get advice on the production, we interviewed professor Lili Wang from the business school of Sichuan University. After we introduced our project, prof. Wang suggested that we conduct market research to determine product positioning. At the same time, she suggested that we adopt the OEM model to reduce production costs. Besides, considering the distrust of some public, especially consumers of health products, towards GMO (Genetically Modified Organisms) products, prof. Wang suggested that we mark GMO products but not highlight them in publicity. We also added the public's attitude towards GMO into the questionnaire survey.
This consultation led us to a number of actionable recommendations on production and marketing, which helped shape our human practices in the further stages of the project.

Prof. Zhimin Yang

In order to avoid possible legal disputes during the project, we consulted Zhimin Yang, a professor of law at Sichuan University, in the early stage of the project. Since our subject referred to the literature of Shanghai Institute of Life Sciences, Chinese Academy of Sciences, prof. Yang suggested that we check whether there are relevant patents. Later, we found that the author of the paper has applied for the relevant patent. If our strain wants to be further commercialized, we need to negotiate with the patent holder.
At the same time, prof. Yang told us that China's laws about patent protection of traditional culture are constantly improving. Patented technology inspired by Chinese traditional culture needs to be approved by the relevant national institutions after relevant regulations come into force. Because cordycepin is an effective component of Chinese medicine Cordyceps militaris, we need to pay attention to the relevant regulations.