He has a profound understanding of the "negative" regulation of the immune system, which is crucial for designing an "enhancing" adjuvant that doesn’t get "overactivated."
Finally, it’s Liu Yang’s turn. He speaks briefly but confidently: "Liu Yang, Doctor at the Fourth Military dical University, specializing in biochemistry and molecular biology. Skilled in techniques such as gene cloning, vector construction, protein expression and purification, site-directed mutagenesis, and protein interaction studies, and also proficient in operating various chromatography and mass spectrotry equipnt and maintaining animal models."
He is the technical cornerstone of the team, responsible for turning ideas into tangible molecules.
While listening, Yang Ping quickly aligns this information with the files he has read and sketches out their potential roles within the team in his mind.
Their knowledge structures indeed complent each other. Jiang Jitong is an experienced jack-of-all-trades and potential coordinator, Chu Xiaoxiao and Wang Chao focus on the front and back ends of immune applications, Mao Mingcheng emphasizes immune balance and chanisms, and Liu Yang provides robust molecular technology support.
"Very good." After everyone finished their introductions, Yang Ping nodded, showing little expression but approval in his eyes. "Welco everyone to this new project team. The goal of our project, briefly ntioned during your recruitnt, will now be clearly stated: to develop a novel ’modular protein molecule adjuvant’ with broadly enhanced antigenic effect. Strictly speaking, it can’t be called an adjuvant anymore." He deliberately emphasized "protein molecule" to highlight its design attribute.
He stood up, walked to a whiteboard, picked up a black marker pen, started writing and drawing, and soon a simple diagram appeared, which looked more impressive than what was in the lesson plan.
"Traditional vaccine adjuvants like aluminum adjuvants, MF59, AS01, etc., all have their pros and cons. Most have relatively simple chanisms or raise safety concerns. More importantly, they have limited universality, with unstable enhancent effects on different antigens. Additionally, the self-comparison of past adjuvant research is rather poor." He drew a circle on the left side of the whiteboard, wrote "traditional adjuvant" inside, and added a question mark.
"Our idea is to think outside this box and adopt a modular design."
He drew two side-by-side rectangles in the center of the whiteboard, connected by a bidirectional arrow.
"The first module is the ’Enhancer Design Module.’" He pointed to the left rectangle. "The core is to utilize gene recombination technology to design and synthesize a brand new protein molecule that doesn’t exist in nature. The core function of this molecule is to precisely and efficiently enhance antigen-specific immune responses. It needs to possess several key characteristics." He quickly listed the key points inside the rectangle:
"First, targeting: Can efficiently and specifically bind to antigen-presenting cells, such as specific receptors on dendritic cells and macrophages, to avoid off-target effects."
"Second, internalization and processing: Can promote the efficient endocytosis of antigen-enhancer complexes by APCs and enter appropriate antigen processing and presentation pathways, mainly MHC-I and MHC-II molecules presentation pathways."
"Third, activation signal: While binding and internalizing, can provide a strong and controllable co-stimulatory signal to maximize APC activation, enabling maturation, high expression of CD80, CD86, and secretion of appropriate cytokines like IL-12 to guide Th1 type immune response."
"Fourth, safety: The molecule itself should have low immunogenicity to prevent eliciting a strong immune response against the enhancer itself, which could cause unnecessary side effects."
The pen on the whiteboard made a rustling sound while the black lines outlined a clear logical frawork.
The five individuals kept their eyes glued, especially the four newcors who were extrely focused; Chu Xiaoxiao even began preliminarily sketching similar diagrams in her notebook. Wang Chao occasionally pushed up his glasses, furrowing his brows, seemingly contemplating how viral antigens could fit into this system.
"The second module, the Bridge Modularity Mounting Module." Yang Ping moved his pen to the right rectangle. "We need to develop a connection technology that is efficient, stable, and highly universal, whether chemically or biologically, to allow our designed enhancer protein to be mounted onto different vaccine antigens as if hanging a coat securely, specifically, and without affecting either party’s function—be it viral surface protein, tumor antigen, or any other target we aim to immunize." He also listed the requirents inside this rectangle:
"First, efficiency and stability: Connection efficiency should be high, with the chemical bond or interaction ford being stable enough to maintain over ti in the complex conditions within the body, ensuring the enhancer and antigen reach the lymphoid organs together and get captured by the sa APC."
"Second, site-specific: Preferably achieve site-directed conjugation to prevent random connections leading to the enhancer’s or antigen’s critical functional domains being masked or inactivated."
"Third, universality and flexibility: This mounting system must be foolproof and modular enough to ensure that when developing vaccines for different diseases in the future, we only need to change the antigen part, while keeping the enhancer and connection thod the sa, greatly reducing R&D costs and duration."
"Fourth, mild compatibility: Connection reaction conditions must be mild, not disrupting the protein’s spatial structure and biological activity."
Yang Ping circled the bidirectional arrow between the two rectangles: "These two modules are the core cornerstones of the project, complenting each other and indispensable. When designing the enhancer, it must be considered whether it is easily mountable and structurally has suitable sites for modification. When designing the bridge, it must also ensure it doesn’t interfere with the enhancer’s targeting and activation functions."
He put down the pen, turned to face everyone, his gaze becoming serious: "The challenges of the project are quite apparent. First, this enhancer protein is designed from scratch, starting with the amino acid sequence, requiring computer simulation to predict its 3D structure, binding ability with receptors, stability, etc., followed by experintal validation and optimization—this is a repetitive trial-and-error, continuous iteration process. Second, the bridge technology has to et all the above stringent conditions to find an optimal solution. Currently, there is no perfect ready-made solution available for us to use directly on the market. We might need to modify or even invent a new connection thod ourselves."
The eting room was silent, save for the faint sound of the air conditioning system continuously running.
The five hadn’t anticipated that following a simple self-introduction, the project would officially comnce, especially with a Nobel Prize winner personally explaining the project on stage.
They quickly jotted down important points with their pens.
"No need for everyone to take notes; I’ve prepared so materials for you to study. Through study, you’ll gain a basic understanding of this project and the surrounding technologies. It’s okay if you’re not familiar; start learning now, study during research, research while studying."
Yang Ping set down the whiteboard marker, reached into the docunt bag he just brought, and took out a thick stack of materials, which Jiang Jitong promptly walked up to receive.
"Distribute these. From now on, we’ll et at four every afternoon in this eting room to discuss the project. This isn’t a warm-up; the project starts officially now. Don’t worry if you don’t know anything—this is how cutting-edge projects are, without references, full of uncertainties. If there were ready references, would it still be a cutting-edge project?"
"Whatever opinions you have, feel free to express them anyti. Jiang Jitong, create a group where we can discuss ideas 24/7, even if they’re not entirely ford."
"Don’t ever be afraid of being laughed at."
While Jiang Jitong distributed the materials, Yang Ping encouraged everyone, acknowledging that these doctors undoubtedly had the basic knowledge. For the research on frontier projects, many practical thods and tools needed to be learned while conducting experints.
Everyone received a copy of the materials, which included a brief experintal plan and design points. These points were not scattered; Yang Ping had already connected them with logical relationships using a mind map.
At the end of the materials, there were also recomnded must-read monographs and papers.
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