godfather of surgery

Chapter 1241 Five Hundred Million

In martial arts, speed is the ultimate weapon. These PhDs never expected the professor to act so quickly, without any warm-up, mobilization, or any preparatory actions, and they went straight into action.

After listening to the professor's introduction, Jiang Jitong spoke up at the opportune moment: "Professor, regarding the design of enhancer proteins, could we adopt a functional domain jigsaw puzzle strategy? From the known structures of proteins with immunomodulatory functions, could we extract specific receptor-binding domains, such as the recognition domain of TLR ligands, membrane-penetrating or internalization signaling domains, and co-stimulatory signaling domains, and connect them through appropriate flexible linkers to construct a multifunctional chimeric protein? Then, could we use structural prediction tools such as AlphaFold2 for preliminary screening, and then verify the function through in vitro experiments?"

The four new PhD students immediately turned their attention to them. The senior student was being a bit far-fetched; such an immature suggestion shouldn't have been made in this setting.

They thought that if their former mentors had heard such far-fetched ideas, they would have given them a good scolding: "Use your brain, okay? Say something practical!"

At this moment, everyone couldn't help but worry whether Senior Brother Jiang would get scolded.

However, Professor Yang gave him an approving look and nodded: "Your suggestion is excellent, though difficult to implement. But if it weren't difficult, would it be called a research project? Would it require gathering so many brilliant minds and spending so much money to conduct it full-time? Everything requires thinking before doing; you only get results by trying things out."

“Just like building a complex model with Lego bricks, we need to select the optimal combination of functional domains, linker length, and order. Liu Yang!” Professor Yang looked at the molecular technology expert. “You will be mainly responsible for the design of protein gene sequences, codon optimization, plasmid vector construction, and the establishment of mutant libraries. You need to build an efficient and rapid molecular cloning platform.”

Liu Yang immediately straightened his back and said in a loud voice, "Understood, Professor! Mission accomplished!"

That's what they say, but Liu Yang's mind was completely blank when it came to actually doing it. However, he steadied himself and remembered what the professor had said: If something is clearly understood and still considered a cutting-edge topic, then it's just copying homework.

“Chu Xiaoxiao and He Zijian,” Yang Ping turned his gaze to the two newcomers with immunology backgrounds, “In the early stages, you will assist Liu Yang by providing suggestions on the selection and design of enhancer protein functional domains from the perspective of immunological functional requirements. For example, from the perspective of T cell activation, consider which co-stimulatory signals are most critical. Wang Chao, you will consider how to promote cross-presentation from the perspective of viral antigen presentation. In the later stages, you will need to establish corresponding functional verification models.”

"Okay, Professor!" Chu Xiaoxiao, He Zijian, and Wang Chao said in unison, feeling the weight of responsibility on their shoulders become more concrete.

“Chu Xiaoxiao,” Yang Ping said, looking at the girl researching autoimmunity, “your task is crucial. You will be responsible for the in vitro immunological functional verification and high-throughput screening of the enhancer proteins. Once Liu Yang and his team construct and express the candidate proteins, you will need to quickly establish activation detection models based on human or mouse dendritic cells and macrophages to assess the effects of these proteins on the expression of co-stimulatory molecules on the APC surface, cytokine secretion, antigen phagocytosis, and processing capabilities. At the same time, you will also need to establish a preliminary safety assessment model to detect whether it will induce unnecessary cytokine storms or autoimmune tendencies.”

Chu Xiaoxiao took a deep breath and nodded vigorously: "I understand, Professor! I will set up these platforms as soon as possible." She realized that her work was directly related to the life and death of the candidates, and the responsibility was heavy.

She never expected that she would be doing something so important right away after arriving here. In her mind, this kind of research was usually undertaken by scholars of considerable stature, such as those who have been awarded the title of Outstanding Young Scientist. She was only there to do the specific work.

Construction? Such a high-level task, how could it possibly be her turn? She didn't even have time to process it, but her mouth was faster than her brain, and she had already said it.

"Professor, you have such a good memory! You remembered all our names right away," Chu Xiaoxiao suddenly blurted out.

Yang Ping was taken aback. This little girl, I can't even remember a few of her names, is her IQ that low?

Chu Xiaoxiao chuckled. As the only girl in the research group, she was destined to be a darling in the future.

"As for the bridging technology," Yang Ping's gaze finally settled on Jiang Jitong, "Dr. Jiang, you'll be in charge of this. Currently, there are several mainstream approaches, such as gene fusion expression, the biotin-avidin system, various short peptide tag pairing systems, and chemical conjugation methods. You'll be responsible for a comprehensive survey of the advantages, disadvantages, costs, efficiency, and specificity of existing technologies. Combining this with the characteristics of our enhancers and different types of antigens, you'll propose several of the most feasible technical routes and conduct preliminary verification experiments. Wang Chao," he called Wang Chao again, "your background in virology is very helpful in understanding the structural characteristics of viral antigens and their surface modifiable sites. You'll assist Dr. Jiang, focusing on evaluating the potential impact of different linking methods on viral antigen conformation and immunogenicity. In short, everyone has their own tasks, but we must cooperate, leverage our strengths and avoid our weaknesses. Each person's task is clear, but we cannot be isolated from each other."

“No problem, Professor! I’ll start the literature review and design immediately.” Jiang Jitong answered decisively, demonstrating his determination to live up to the mission.

Wang Chao immediately replied, "I will fully cooperate with Dr. Jiang's work."

As everyone gradually got into the zone, the initial timidity lessened considerably.

Yang Ping's arrangements were clear and specific, tightly coupling the background knowledge and skills of the five people with the two core modules of the project, so that everyone knew their specific position and responsibilities in this grand plan, thus avoiding initial confusion and internal friction.

"The next one to two months will be our proof-of-concept and initial exploration phase, which is also the most crucial foundation-laying stage." Yang Ping returned to his seat, opened his laptop, and sent a more detailed preliminary experimental plan and timeline to the research group's group chat via the internal system. "This is the preliminary plan; you can take a look first. I will be in the office frequently. If you have any questions, whether it's technical bottlenecks or confusion in your thinking, you can come to me to discuss them at any time. Our group will have a small meeting once a day and a summary meeting once a week. Dr. Jiang will send the specific schedule to the group chat. The purpose of the meetings is mainly to report progress, focus on discussing the difficulties encountered, and share the latest literature. I don't like formalism; I want to see solid data and thinking. We must abandon all formalism, be pragmatic, and truly and steadily devote ourselves to this project."

He paused, his tone becoming unusually serious, his gaze sweeping across the room again: "I must emphasize again that there is no ready-made path for this research. I hope everyone can completely forget about student thinking, summon the courage of pioneers and 200% focus, dare to hypothesize, dare to design, and even more so, dare to use rigorous experiments to verify and refute them. I am not afraid of you making mistakes; experimental failure is normal, and negative data is also a result. But what I cannot tolerate most is rigid thinking, being afraid to think, being afraid to try, or falsifying data in pursuit of impressive results. Our goal is to create something truly usable, understand? You must remember that any experiment may fail, and failure is also a result."

"Understood!" the five replied in unison, their voices even louder than before, filled with a passion that had been completely ignited.

"Furthermore, the artificial intelligence at Nandu Medical University is fully open to the five of you. You can use AI or digital human technology without prior appointment. The same applies to the supercomputing center at Nandu Polytechnic. You will have absolute priority access without appointments or queuing, with no limit on time or number of uses."

Is that so? Everyone was in high spirits, especially Chu Xiaoxiao, whose big eyes behind her black-rimmed glasses shone brightly.

At this moment, the newlyweds were filled with thoughts, their notebooks were full of dense notes, and their chests were surging with fighting spirit.

Yang Ping leaned back slightly, looking calmly at Jiang Jitong: "Director Tang should have already explained it to you, right?"

Jiang Jitong nodded: "Professor, Director Tang instructed me to take on more coordination work." Yang Ping nodded, his tone calm yet carrying undeniable weight: "In this group, you are the most experienced and have handled the most problems. I don't want to be too preoccupied with the trivialities of daily lab management, so you need to put in the effort to help me get the team running smoothly, streamline the workflow, and help these newcomers grow up quickly and become independent. If you encounter difficulties in experiments or technology that your group cannot resolve internally, or if you need me to coordinate resources within the institute or even outside the university, come directly to me. You are now the daily head of the research group."

Jiang Jitong understood immediately and assured him sincerely, "Professor, rest assured, I know what to do. I will do my best in internal coordination, service and support to ensure smooth information flow, efficient use of resources, and get the whole team running like a precision instrument as soon as possible. I will never let trivial matters bother you."

“Hmm,” Yang Ping said noncommittally, then asked, “Leaving aside these management issues, just looking at the project itself, what more specific and preliminary technical ideas do you have for these two modules, especially the connecting bridge part that you are responsible for?”

Today is only the first day, the first meeting. How could Senior Brother Jiang possibly answer? Everyone couldn't help but feel worried for Jiang Jitong.

Everyone thought the first day of the meeting would be a mobilization meeting, with some slogans to be shouted, and that we would prepare for another month or two before gradually developing the research topic. Little did they know that the first day would be the real deal.

Jiang Jitong had made thorough preparations long ago. He took a deep breath and said:
"Professor, your modular approach dictates that the linker technology must be highly versatile and flexible. My preliminary analysis suggests that while gene fusion expression may seem like a one-time solution, it could affect the structure and function of both enhancers and antigens, and it lacks flexibility. The biotin-avidin system is highly specific and binds firmly, but it is costly, and exogenous avidin may introduce unnecessary immunogenicity. Traditional chemical conjugation, such as the NHS/EDC method, involves relatively harsh reaction conditions, which can easily lead to protein inactivation, and the linker sites are random and difficult to control."

He paused briefly, observed Yang Ping's reaction, and seeing that the other was simply listening quietly, he continued to delve deeper:

"Therefore, I personally prefer to explore the possibilities of enzymatic ligation. For example, we can engineer existing, efficient ligase systems to optimize their catalytic efficiency, substrate specificity, and mild reaction conditions. Or we could even try to design a minimal peptide or protein building block with ligation function from scratch to achieve site-specific, rapid coupling under near-physiological conditions. This path is more difficult, but if successful, its innovation and applicability will be revolutionary. We can start by modifying existing systems while simultaneously exploring cutting-edge directions for entirely new designs."

After listening, Yang Ping tapped his fingers lightly on the table twice. His face remained expressionless, but a faint hint of appreciation seemed to flash in his eyes. Only one day had passed since the change of personnel, yet he was able to answer the questions so comprehensively and in-depth, which showed that in addition to his solid foundation, he had made the most thorough preparations immediately after receiving the task.

"The idea is good, not conservative. Scientific research requires daring to think. Now that you have a direction, go ahead and design experiments to verify it. If you need specific enzymes, mutant libraries, or to communicate with collaborators, you don't need to write a report. Just send me a WeChat or phone call, and I'll take care of it."

"Yes! Thank you, Professor!" Jiang Jitong was quite excited.

"Everyone, please remember that in the future, if you need funding, technology, or special connections, you don't need any written reports. That would be too slow. Just say it in the WeChat group," Yang Ping added.

He now needs to adopt an internet-based mindset when conducting research, as traditional procedures are simply too slow and cumbersome.

"Do you have anything to say? You can speak about technical or management aspects without feeling pressured," Yang Ping said, looking at the other four people.

Senior Brother Jiang made thorough preparations, but they didn't. They never imagined they would have such an important task with such a high-level research project; they thought they were just there to make up the numbers.

"It's okay, it's normal that you can't express your opinions now. When you get back, take some time to read the papers and monographs I listed for you. After you've read them, you'll understand a lot more. If you have any questions, feel free to discuss them in the WeChat group." Yang Ping didn't blame them at all for not being able to offer any opinions.

Seeing Professor Yang's tolerance, everyone's worries and tension lessened considerably.

"Professor, I have a question?"

Chu Xiaoxiao raised her hand.

"Say it!"

"I'd like to ask how much research funding we have?"

Yang Ping thought for a moment: "Oh right, I haven't told you about our research funding yet. I haven't paid much attention to it. I need to check the initial budget."

Yang Ping took out several more documents from his briefcase and looked at them one by one. It seemed that the amount of funding was on one of the documents.

He searched for a long time before finally finding the number. He pulled out the piece of paper and pointed to the number: "Initial funding - 5 million."

5 billion!

Jiang Jitong was alright; he was a senior researcher at the institute and had seen such grand occasions before.

The other four PhDs were so shocked their eyes almost popped out.

"This is the initial stage; we'll add more as the progress goes on. Five hundred million definitely won't be enough." Yang Ping put away the paper.

Chu Xiaoxiao counted on her fingers. Apart from Professor Yang, there were exactly five of them. So, on average, each person would receive one hundred million.

Oh my God!