godfather of surgery

Chapter 1240 The project has officially begun.

The final list has been finalized. Compared with the initial list, Ji Ning has been replaced by Jiang Jitong, while the other personnel remain unchanged.

Jiang Jitong is experienced and has comprehensive knowledge. He was a key member in the original research project, and Yang Ping would never have transferred such a person to the new research group before.

However, Tang Shun told him that Ji Ning was worried that his knowledge of immunology was too weak, so he changed his mind at the last minute. There was nothing Tang Shun could do. After thinking it over, Tang Shun could only spare the time for Jiang Jitong. Moreover, Jiang Jitong himself was very interested in immunology. This arrangement was very reasonable and the best arrangement under the current conditions.

Since that's the case, Yang Ping didn't say anything more. Having a senior PhD in the research group would make things much easier for him.

The first group meeting of the new research group was held in the small conference room of the laboratory.

When Yang Ping arrived, he found that all five people were already there, and not only were they all there, but they also seemed to be arranged according to some kind of invisible seating order.

Jiang Jitong sat in the seat closest to the head of the table, with a thick leather notebook and a pen spread out in front of him. He was calm and composed, with a sharp gaze that carried just the right amount of respect.

The other four newcomers sat a little further away, looking somewhat reserved, with their backs straight and their notebooks in front of them being the standard lab notebooks, their brand-new covers still reflecting the light.

Upon seeing Yang Ping enter, the five of them stood up simultaneously, their movements perfectly synchronized, as if they had rehearsed beforehand, indicating that they had done a thorough job of preparation.

"Sit down," Yang Ping said gently, and then sat down.

Apart from Jiang Jitong, the other four were indeed complete newcomers. Yang Ping had met them relatively few times and was not very familiar with their faces.

Of course, He Zijian is an old classmate, but we haven't seen each other much lately.

Chu Xiaoxiao, a female PhD student, has a neat ponytail, clear and focused eyes, and a hint of a competitive spirit.

Wang Chao, wearing black-rimmed glasses, was slightly thin, but looked quite energetic.

Liu Yang was the tallest among them, standing at 1.89 meters, and appeared sunny and lively.

He Zijian has a more gentle demeanor, but his slightly pursed lips reveal his seriousness and determination.

They all seemed to be in good spirits, indicating that they had all volunteered for the new project and were not forced to work with negative emotions. Yang Ping dislikes working with negative emotions the most; if you don't like the work, it's hard to do it well, and even if you do, it's extremely difficult.

“Everyone’s here, let’s get to know each other first.” Yang Ping said in a calm tone, “My name is Yang Ping, and I will be the person in charge of this project from now on. We will be working together for a while. Please introduce yourselves: your name, your alma mater, your main research background, and your areas of expertise. Don’t be too formal, just give a brief introduction.”

Everyone couldn't help but laugh. Professor Yang was so humorous; did he even need to introduce himself?

Jiang Jitong cleared his throat, his voice loud and clear: "Jiang Jitong graduated from Nandu Medical University, and his main research focus was stem cell therapy. I was fortunate to participate in some of the early major projects of our institute and have mastered various advanced research methods. At the same time, I have always had a strong interest in immunology, especially in the field of immunoengineering, and I have accumulated some knowledge in this area. I am very honored to join this brand-new research group, and I believe that under Professor Yang's leadership, we will definitely make breakthroughs."

His presentation was well-structured, highlighting his extensive experience and interdisciplinary skills while cleverly leveraging his stem cell background as an advantage, and emphasizing his strong interest in immunology. After all, interest is the best motivation.

Jiang Jitong is quite clever. Even before meeting Professor Yang, his research group had just been formed, and he had already found his right place. He would lead four junior students in experiments and become Professor Yang's capable assistant. It was he who arranged for everyone to have notebooks just now.

Next came the self-introductions of the newcomers, who seemed somewhat reserved.

Chu Xiaoxiao was the only woman among the five. She spoke quickly and efficiently: "Chu Xiaoxiao graduated from Beijing Medical University. During her doctoral studies, she mainly researched the T cell exhaustion mechanism in the tumor microenvironment, focusing on exploring potential new targets for checkpoint inhibitor combination therapy. She is proficient in flow cytometry, ELISPOT, and in vitro T cell activation and killing models."

Her presentation closely followed the core of immunology, with a clear list of techniques and well-defined objectives, demonstrating that she was a perfect fit for the research topic.

Wang Chao adjusted his glasses and continued, "Wang Chao, PhD, graduated from Fudan University School of Medicine. His research focuses on the replication mechanisms of influenza viruses, coronaviruses, and other viruses, as well as the escape of host innate immune responses. He is skilled in viral packaging, pseudovirus system construction, RT-PCR, Western blotting, and related bioinformatics analysis."

His background leans towards pathogens, which is directly related to vaccine development, and he is the representative of the virology field in the team.

Although Yang Ping did not make any specific requirements, Tang Shun fully considered the combination of different majors when selecting personnel, so as to make up for each other's weaknesses.

He Zijian's voice was relatively gentle, but his content was solid: "He Zijian, PhD, graduated from West China University of Medical Sciences. His research focuses on the pathogenesis of autoimmune diseases, including the production of autoantibodies, deposition of immune complexes, and abnormal activation of the complement system. He is familiar with autoimmune mouse models, immunofluorescence, tissue staining, and the detection of various cytokines."

He has a deep understanding of the “negative” regulation of the immune system, which is crucial for designing an adjuvant that “enhances” but does not “over-activate” the immune system.

Finally, Liu Yang spoke concisely, yet with an air of confidence: "Liu Yang, PhD from the Fourth Military Medical University, specializing in biochemistry and molecular biology. He is skilled in gene cloning, vector construction, protein expression and purification, site-directed mutagenesis, protein-protein interaction research, and is also proficient in operating various chromatographic and mass spectrometry equipment and maintaining animal models."

He was the team's technical cornerstone, responsible for turning ideas into tangible products. As Yang Ping listened, he quickly compared this information with the files he had reviewed, and began to sketch out their potential roles within the team.

Their knowledge structures are indeed complementary. Jiang Jitong is an experienced all-rounder and a potential coordinator, Chu Xiaoxiao and Wang Chao focus on the front and back ends of immune applications, He Zijian focuses on immune balance and mechanisms, and Liu Yang provides strong molecular technology support.

“Very good.” After Yang Ping and the others finished their introductions, he nodded, his face showing little expression, but his eyes conveyed approval. “Welcome to this new research group. The goal of our project was briefly mentioned when we recruited you, but I will reiterate it now: to develop a novel 'loaded protein molecule adjuvant' with broad-spectrum antigen-enhancing effects. Strictly speaking, it can’t be called an adjuvant.” He deliberately emphasized “protein molecule” to highlight its design attributes.

He got up, walked to a whiteboard, picked up a black whiteboard marker and began to write and draw. Soon a simple drawing was completed, and the black and white sketch was even more beautiful than the one in the textbook.

“Traditional vaccine adjuvants, such as aluminum adjuvants, MF59, and AS01, each have their own advantages and disadvantages, but most of them have relatively simple mechanisms of action or safety concerns. More importantly, their universality is limited, and their enhancement effect on different antigens is unstable. Furthermore, historically, adjuvant research has been relatively scarce.” He drew a circle on the left side of the whiteboard, wrote “traditional adjuvants” inside, and added a question mark.

"Our approach is to think outside the box and adopt a modular design."

He drew two boxes side by side in the center of the whiteboard, connected by a double-headed arrow.

“The first module is the ‘enhancer’ design module,” he pointed to the box on the left. “The core is to use gene recombination technology to design and synthesize a completely new protein molecule that does not exist in nature. The core function of this molecule is to precisely and efficiently enhance the antigen-specific immune response. It needs to possess several key characteristics.” He quickly listed the key points in the box:
"First, targeting: It can bind to specific receptors on the surface of antigen-presenting cells, such as dendritic cells and macrophages, efficiently and specifically, avoiding off-target effects."

"Second, internalization and processing: It can promote the efficient internalization of antigen-enhancer complexes by APCs and enter the appropriate antigen processing and presentation pathways, mainly the MHC-I and MHC-II molecule presentation pathways."

"Third, activation signal: While binding and internalizing, it can provide a strong and controllable co-stimulatory signal to maximize the activation of APC, enabling it to mature, highly express molecules such as CD80 and CD86, and secrete appropriate cytokines such as IL-12 to guide the Th1 immune response."

"Fourth, safety: The immunogenicity of the molecule itself should be as low as possible to avoid triggering a strong immune response against the enhancer itself and causing unnecessary side effects."

The pen scratched across the whiteboard, and black lines outlined a clear logical framework.

The five people's eyes followed closely, especially the four newcomers, who listened with great concentration. Chu Xiaoxiao had even begun to quickly draw similar diagrams on her notebook, while Wang Chao would occasionally push up his glasses and furrow his brows, seemingly pondering how the viral antigens could adapt to this system.

“The second module is the bridge mounting module.” Yang Ping moved his pen to the right-hand box. “We need an efficient, stable, and highly versatile chemical or biological linking technology. This technology should be able to stably, specifically, and without affecting the function of either the enhanced protein we designed, like hanging clothes on a hook, onto different vaccine antigens—it could be a viral surface protein, a tumor antigen, or any other target we want to immunize against.” He also listed the requirements in this box:
"First, high efficiency and stability: The connection efficiency must be high, and the chemical bonds or interactions formed must be stable enough to be maintained for a period of time in the complex environment of the body, ensuring that the enhancer and antigen can reach the lymphoid organs together and be captured by the same APC."

"Second, site specificity: It is best to achieve site-specific coupling to avoid random connections that could mask or inactivate key functional domains of enhancers or antigens."

"Third, versatility and flexibility: This mounting system must be user-friendly and modular enough to ensure that when we develop vaccines for different diseases in the future, we only need to replace the antigen part, while the enhancer and linker method can remain unchanged. This will greatly reduce the research and development costs and cycle."

"Fourth, mild and compatible: The ligation reaction conditions must be mild and should not destroy the spatial structure and biological activity of the protein."

Yang Ping drew a circle on the double-headed arrow between the two boxes: "These two modules are the core foundation of the project, complementing each other and indispensable. When designing enhancers, we must consider whether they are easy to mount and whether there are suitable sites in the structure for modification. When designing connecting bridges, we must also ensure that they do not interfere with the targeting and activation functions of enhancers."

He put down his pen, turned to face the crowd, and his gaze became serious: "The difficulties of the project are obvious. First, this enhancer protein is designed from scratch, starting with the amino acid sequence. We need to use computer simulations to predict its three-dimensional structure, its binding ability to the receptor, its stability, etc., and then verify and optimize it through experiments. This is a process of repeated trial and error and continuous iteration. Second, the bridging technology needs to find the optimal solution under all the above stringent conditions. Currently, there is no perfect ready-made solution on the market that we can use directly. We may need to modify or even invent a new bridging method ourselves."

The conference room was so quiet you could hear a pin drop; the only sound was the faint hum of the air conditioning system.

The five people never expected that after a simple self-introduction, the research project would officially begin, with a Nobel laureate personally explaining the project on stage.

They quickly scribbled down important points with their pens in the audience.

"No need for everyone to take notes. I have prepared some materials for everyone to study. After studying them, you will have a basic understanding of this topic and the related technologies. If you don't know them, that's okay. If you don't know them, you can start learning now. Learn through research and research through learning."

Yang Ping put down the whiteboard marker and took out a thick stack of documents from the briefcase he had just brought. Jiang Jitong immediately went up and took them from him.

"Distribute these materials. From now on, we will meet in this conference room every afternoon at four o'clock to discuss the research topic. This is not a warm-up; the research topic is officially starting now. Don't worry about not knowing anything right now. This is how cutting-edge research is. Without reference, you'll be completely lost. If there were readily available references, would it still be a cutting-edge research topic?"

“Everyone is welcome to express their opinions at any time. Jiang Jitong has created a group chat where we can discuss things 24 hours a day. We can share our ideas, whether they are mature or not.”

"Never be afraid of being laughed at."

While Jiang Jitong was distributing the materials, Yang Ping encouraged everyone, saying that these doctoral students certainly had no problem with basic knowledge. For cutting-edge research topics, there are many practical methods and tools that they need to learn while conducting experiments.

Everyone received a document containing a brief plan for the experiment and key design points. These points were not scattered; Yang Ping had already connected them logically using a mind map.

The materials also include recommended monographs and papers that you should definitely read.