Character Interview Chen Nan: Big Brother of the Laboratory, Pioneer in the Industry

Dr. Chen Nan, born in Xinyang City, Henan Province, graduated from the School of Chemistry and Molecular Engineering, Zhengzhou University in 2013 with a bachelor's degree; in 2019, graduated from the School of Chemistry and Molecular Engineering, Peking University with a Ph.D. From Professor Wang Chu, the main research direction during his Ph.D. period was chemical proteomics. At the beginning of 2019, he went to the research group of Professor Tarun M. Kapoor of Rockefeller University to do post-doctoral research. The main research direction is chemical proteomics. At the same time, he also conducts research including the design of protein covalent inhibitors and protein structural biology. After returning to China in early 2021, Dr. Chen Nan invested in the industry and co-founded Nanjing Coluosi Biotechnology Co., Ltd., and currently serves as the general manager.

1. About the research topic

Old sheepskin: Brother Chen Nan, as the first student of Teacher Wang Chu, was also the leader who took me into chemical biology. In 18 years, I participated in the research of phosphopantetheine of Chen Nan. Brother Chen Nan’s rigorous experimental design and meticulous data analysis have benefited me a lot. After seeing Nan Ge again after two years, let Nan Ge first introduce his scientific research experience along the way, and why Nan Ge chose chemical biology among the many branches of chemistry.

Chen Nan: I entered the School of Chemistry and Molecular Engineering of Zhengzhou University as an undergraduate. My major is chemistry. During the school, I was fortunate to have participated in more than two years of scientific research in the research group of Teacher Li Gang. I really like the feeling of scientific research and exploration and creating new materials. After that, I passed the summer camp assessment of the School of Chemistry and Molecular Engineering of Peking University, and had the opportunity to work on a graduation thesis with Mr. Xiaoyu Li (currently working at the University of Hong Kong), and I was exposed to chemical biology for the first time. In fact, I didn't have much understanding of this novel subject at that time. I just felt that it was a promising interdisciplinary subject, and I learned a lot of knowledge that hadn't appeared in the textbook.

After officially enrolling in Peking University in 2013, he entered the research group of Professor Wang Chu of the Department of Chemical Biology, and his main research direction is chemical proteomics. At that time, there was actually no research group in China to carry out a similar research direction. Teacher Wang Chu was the first to bring this research field into China. For this reason, I felt very honored to be able to get in touch with the very cutting-edge technology in the world. Nowadays, the development and application of chemical proteomics technology are obvious to all. My Ph.D. research work is mainly to use chemical proteomics technology to analyze two types of important post-translational modifications in cells on a large scale. One is protein N-homocysteinylation modification, which is closely related to clinical hyperhomocysteinemia; the other is phosphopantetheinylation, referred to as "pantothening" modification, which is a type of cellular metabolism Required post-translational modifications. In response to these two modifications, I developed corresponding chemical and metabolic marker molecular probes, and combined with quantitative proteomics technology for the first time in mammalian cells the systematic identification of modified substrates and sites for these two types of modifications. . In addition, I was also responsible for some cooperative topics and horizontal projects, using chemical proteomics technology for drug target identification.

After graduating from my Ph.D., I went to Rockefeller University to engage in post-doctoral research. The main direction was chemical proteomics. At the same time, I also carried out some new research directions, including the design of protein covalent inhibitors and protein structural biology research. At the end of March this year, I just returned from New York, USA, and founded the current company with my partners, Nanjing Coross Biotechnology Co., Ltd. In the future, I will devote all my energy and time to make this company a success.

2. What kind of experience is it like to be a big brother

Lao Sheepskin: We all know that Nan Ge is the first doctoral student of Mr. Wang Chu and participated in the whole process of the creation of Mr. Wang Chu's laboratory. What impressed me most was that when buying reagents, mentioning Brother Chen Nan’s name could be given an additional discount, which also proved Nan Ge’s "status" in the Wang Chu teacher group. So, Brother Nan, how does this experience of participating in the establishment of the group feel for you?

Chen Nan: The overall feeling is summed up in one word-there are gains and losses. Let me first talk about the "get" aspect, there are three points: First, I can participate in the change from 0 to 1 in the laboratory. I actually entered our laboratory earlier than Mr. Wang Chu. After Mr. Wang Chu's laboratory was assigned, in fact, I was from the United States. I was the first to enter the laboratory. From the very beginning, a desk and a computer, to the time when I graduated, there were more than a dozen juniors and juniors in the laboratory, and the experimental bench was full of familiar instruments that I had used before. This feeling of growing up with the laboratory is unique; The second is to get the personal guidance of Mr. Wang Chu in the experiment. Whether it is from the cultivation of scientific research thinking, or subject thinking, experiment design, and result analysis, I have received the most authoritative guidance from the laboratory, which has a profound impact on my doctoral career; third, I have no senior brothers and sisters to rely on, except for my mentor In addition to the guidance, more often you need to think and try on your own. For example, if you forget to add a control group when you have no experience in the first experiment, you may always remind yourself the next time that you will not make the second and third mistakes. This independent process is very helpful for the improvement of personal ability, and it allows me to grow up quickly and take on my own tasks.

Of course, as the first student in the laboratory, you need to invest time to help Mr. Wang build the laboratory together at the beginning. It requires a little accumulation from the purchase of instruments, debugging, and optimization of experimental procedures, compared with other laboratories. The students in the same class will inevitably have less time to do their own projects. Since the laboratory has no previous accumulation, it also needs to explore the subject area on its own, which also takes more time than others. In addition, the so-called elder brothers, generally in the eyes of the newcomers, are all-powerful character settings in the laboratory, which imposes a lot of pressure on themselves, which requires themselves to pay more and continuously improve their abilities. Only in this way can we really set an example for the juniors and sisters.

Of course, if I have another chance to choose, I still feel that it is a great honor to be the first student in the laboratory, whether it is for my PhD career or my entire life.

3. The most impressive thing in scientific research

Lao Sheepskin: As mentioned earlier, Brother Nan mentioned that as a big brother in the laboratory, he actually lacks the guidance of the senior brothers and sisters that he can rely on. I must have experienced a lot of ups and downs in the five-year doctoral career. In the process of scientific research, there are both the excitement of exploring new things and the loss of not getting the desired results. Presumably, Nan Ge has also walked this way step by step. In the five years of scientific research experience, what are the things that Nan Ge has been impressed by, and what are the reasons behind it?

Chen Nan: Actually, the entire Ph.D. career itself is an unforgettable memory. Whether it is knowledge, experience, or being in the world, it has benefited a lot. Like most PhDs, I spend most of my time in the laboratory. One of the things that impressed me the most during this process was the development of a new subject.

In fact, my Ph.D. research process was not smooth. The first four years were basically at the stage of project exploration. I changed many subjects and tried many methods, but the results were far from what I expected. Of course, I was still under great pressure. Later, when I was discussing a new topic with Teacher Wang, I wanted to be a binding protein for CoA. Because CoA itself is an essential coenzyme factor for cells and interacts with many important proteins, no one has done any analysis of its whole-cell binding spectra. At the beginning, I was very excited after a simple literature search. I felt that this is a more worthwhile direction, and it is also a place where chemical proteomics technology is good. However, with the deepening of the experiment and the comprehensive analysis of the literature, it is found that CoA can form many derivatives. These derivatives have their own binding proteins. According to the experimental design at the time, they cannot be distinguished. Therefore, the final experimental results may not be clear. Answer the questions raised in advance. After many discussions with Teacher Wang, I felt that it might be necessary to optimize the method, but this time will be very long. I was already close to the fifth year, so I was still very tight in terms of time, and I wondered whether to give up directly. This subject. But after all, I have spent a lot of time and experience on this subject, so I am definitely not reconciled, so I read the literature again, thinking about whether I can change the direction and accumulate and utilize the preliminary work.

I have always been interested in protein post-translational modifications, so I focused on CoA-related post-translational modifications, and then slowly noticed the pantothenic acid modification I mentioned above. After discussing with Teacher Wang, he felt that I should understand the biological function of this modification and the previous research methods one by one, and then decide whether to continue this topic. After several more investigations and discussions, I feel that the chemical proteomics analysis of pantothenic acid modification is indeed necessary, and it can solve the problems that cannot be solved by traditional methods. It seems to be a relatively satisfying story.

The reason why this matter impressed me is two aspects: one is the way of cooperation with the mentor. Because Mr. Wang has always focused on cultivating our ability to think independently and design and complete projects, especially the first class of students, who can only rely on themselves in many cases. At this time, you need to think about the solutions all by yourself, and then discuss with experienced instructors. guide. The whole process is done twice with half the effort, which greatly improves the efficiency of problem-solving. This incident told me that, for your own affairs, never think about getting solutions from others. What others can do can be icing on the cake. Asking for help with possible solutions will greatly increase the probability of success, which is what I have always reminded myself of when I do things. The other aspect is the idea of solving the problem. The so-called God closing a door for you will definitely open a window for you. All you need to do is to work hard to find out where this window is. In fact, many times everyone understands this truth, but just because I lack enough patience, here I am also equivalent to imparting some experience to the juniors and sisters in the laboratory based on my own experience. After all, scientific research is definitely not smooth sailing.

4. From academia to industry, the opportunity to establish a company

Lao Sheepskin: After talking about Nan Ge's past scientific research experience, let's talk about Nan Ge's present. After returning to China at the beginning of the year, Nan Ge did not enter the university as we thought, but chose to establish Nanjing Colosse Biotechnology Co., Ltd. and assumed the position of general manager. I want to know the reason and story behind Nan Ge's choice of this direction.

Chen Nan: To be precise, I still haven't completely divorced from academia, because some of our company's customer groups are still research laboratories of universities, hospitals, and pharmaceutical R&D companies. They still have to deal with teachers and students, and they still do basic research. Coross Biology was initiated by Academician Guo Zijian of Nanjing University and called on everyone to do it together. The advisory team includes top research teams in the field of chemical biology at Peking University and Nanjing University. At the end of last year, the advisors and teachers discussed together, and felt that there was an increasing demand for mass spectrometry in both academia and industry. On the other hand, although there are some well-developed proteomics companies in China, they are still at an early stage compared with foreign countries—especially in the chemical proteomics market, few domestic companies have set foot in them. The United States has already had companies with chemical proteomics as its core technology a few years ago, and the market has developed very impressively. At the same time, the national policy also encourages university teachers to transform their achievements so that they can serve the society with technology. In this context, the consultants and teachers had the idea of starting a chemical proteomics company. At that time, I wanted to return to work in China. I have been engaged in related research, and it hit it off. We rely on Jiangsu Nanchuang Institute of Chemistry and Life and Health Co., Ltd., together with our partners, and with the support of consultants and teachers, we established Nanjing Coluosi Biotechnology Co., Ltd.

5. The company's main business and development direction

Lao Sheepskin: The story of the company's creation is indeed wonderful! Indeed, the "14th Five-Year Plan" also pointed out the need to promote the deep integration of production, education and research, and the work of the Nange team also contributes to the national strategy. Naturally, we are also very curious about what kind of company Colosse is, what kind of business it operates, and what direction of development will it choose in a highly competitive but full of opportunities market in the future?

Chen Nan: We position ourselves as the first domestic high-tech enterprise based in the cross-field of chemical biology. The company will focus on cutting-edge chemical proteomics technology, and its main business includes protein chemical labeling technology services. We have the antibody labeling technology developed by ourselves, which can realize the fixed stoichiometric ratio of the non-modified antibody, and the targeted high-efficiency labeling, such as the labeling of fluorescent molecules and rare earth metal complexes. Another technical service project is chemical proteomics technical services. In this regard, university teachers are very interested. We are currently cooperating with some laboratories to provide related technical services to solve the problem of drug or metabolite target identification. We also hope Can produce some good results. Of course, we also need more customer support. We will try our best to solve the problems that can be solved by proteomics. At the same time, we are also engaged in the research and development and production of chemical probes related to protein chemical labeling, bio-orthogonal reactions and other reagents, which can not only meet the needs of the market and solve the current dilemma of high dependence on imports, but also lay the foundation for the company's technical services and research and development.

In addition to the above-mentioned businesses, we also provide drug leading compound screening services for pharmaceutical companies. We know that the molecular fragment-based ligand discovery strategy, also known as fragment-based ligand discovery (FBLD), has been widely used in the identification of drug lead compounds. However, this method is usually limited to a single protein system, so its throughput is greatly limited, and the interaction between the protein and the ligand in the natural state cannot be well simulated. Our chemical proteomics technology can effectively solve this problem. It can directly screen lead compounds in complex biological systems (cell lysates or living cells) to achieve simultaneous analysis of multiple targets, that is to say, revolutionary Brings FBLD into the era of high throughput. In fact, several chemical proteomics companies in the United States have launched similar cooperation with well-known drug research and development companies, using mass spectrometry-based chemical proteomics technology to discover covalent drug lead compounds in living cell systems, hoping to replace as many as possible. Of functional proteins find potential ligand binding pockets and target "undruggable" proteins

Old sheepskin: Exciting work indeed! Compared with traditional proteomics, chemical proteomics introduces exogenous chemical small molecules, which can realize the analysis of proteome more accurately and efficiently, and has exciting application prospects in the fields of drug screening. So how do students who are interested in working in this field understand and join Nange's team?

Chen Nan: Colossus Biosciences hopes to gather talents from all over the world with an inclusive mind. It is determined to promote the cross-integration of chemical, biological and medical research as its mission. It upholds the concept of "talent first, technology first, customer first", and strives to become world-renowned A leading innovative service and R&D enterprise, to be a leader in the development and application of cutting-edge chemical cross-cutting technologies. Our company has now settled in the Life Science and Technology Innovation Park, Qixia District, Nanjing City, with sufficient office and laboratory space. At the same time, we have obtained the support of capital, everything is ready, we only owe the wind, and we are currently in the recruitment stage. We hope that like-minded friends can join us, whether it is an undergraduate, master or doctoral student; whether it is just graduated or has work experience. All like-minded people can contact me directly to build this company together. We currently hope to recruit people in related fields such as antibody labeling, chemical proteomics technical services, proteomics research and biometric analysis. My contact information is 13201777986, and you can directly add me to WeChat.

6. The transition from school to company, the coexistence of risks and opportunities

Lao Sheepskin: As a person who studies and lives in the ivory tower, a company that is more closely in touch with society is a little stranger. It may be enough to concentrate on scientific research in colleges and universities, but it may require more energy to invest in a more complex network of relationships for the creation and operation of a company. I would like to ask how Nan Ge successfully turned into a general manager, and what are the challenges?

Chen Nan: Most of my time in school is engaged in scientific research experiments. I usually only deal with tutors and classmates. The work content and interpersonal relationships are relatively simple. But when you start your own company, you need to communicate with all kinds of people, including employees, investors, partners, and the government. It is still very challenging to deliver the right information to different people. In addition, the biggest challenge for me at the moment is how to make the company run well. Because I just came out of the laboratory and have no relevant work experience before, I have to learn a lot of things from scratch, including how to make a good business plan, and how to clarify the company’s positioning, business and development goals in the future with investors , How to build the company's framework bit by bit, how to design the company's management system and employee compensation system, etc. Fortunately, we have a very strong consultant team, which has given a lot of help in terms of customer resources, talent team, and various policy applications. We have also received strong support from the company’s Nanchuang Research Institute in terms of company registration and personnel recruitment. At the same time, our investors not only provided generous funding support, but more importantly, the company’s initial construction, management, and financial support. We also provided all-round help in other aspects, so our company was able to operate normally in a short period of time and began to cooperate with some customers. Of course, there is a challenge, and there is a passion for struggle. I also believe that with the support of a strong platform behind us, our founding team and employees can make this company better and better.

Lao Sheepskin: From Senior Brother Chen to General Manager Chen, Nan Ge's identity has undergone a big change. So now living in the field of biomedicine, which is in full swing, what insights can Nan Ge have to share with us? With the current rapid development of biotechnology, how will biomedical companies adjust their positioning to face this "big change unseen in a century"?

Chen Nan: Indeed, the domestic biomedical market has developed rapidly in the past two years, and this is also inseparable from the general environment. After all, I have just entered this market, so many opinions are not mature. Let me briefly talk about my own opinions based on the current cognition. Generally speaking, no matter which field you are engaged in, there are both opportunities and risks. In terms of opportunities, because the market is getting bigger, capital, people, and companies are all flowing into this field quickly. For our start-up companies, they are all positive. As long as their technology and products are excellent, there will be no problems with people and money. Of course, the scale of customers is gradually expanding, forming a good cycle. However, the competition has become more intense. The so-called shopping mall is like a battlefield. Start-ups need to quickly improve their strengths in order to withstand the rapid competition, whether it is benign or vicious, or they will be killed by big companies on the same track.

Old sheepskin: Very deep understanding! Today, I am very honored to share with Nan Ge, his experience and stories along the way, and I sincerely hope that Nan Ge's career will flourish! Finally, I will make an advertisement for the big brother for free. Anyone who is interested in Colosse Bio is welcome to contact Nange directly (13120177986)!