First Phase
Interviewee: Li Tang
Introduction
Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
Institute of Materials Science & Engineering, EPFL, Lausanne, Switzerland View more: https://orcid.org/0000-0002-6393-982X/
Looking for
At the initial stage of our project's development, we require the assistance of senior professionals to help us organize the project and provide guidance on conducting experiments. Specifically, we are exploring the application of CAR-T therapy in cancer treatment and are interested in advancing this methodology. Professor Tang, an authority in the field of immunoengineering, has contributed significantly with publications such as 'Metabolic reprogramming of terminally exhausted CD8 T cells by IL-10 enhances anti-tumor immunity' in Nature.
Question we asked
What are the considerations when choosing a topic? What considerations do we have in choosing the topic?
Do we need to consider local practical issues in our research project?
How to distinguish between one's own topic and someone else's topic?
How to effectively search and utilize scientific literature for scientific research work?
How to explain complex scientific research results to the public in a way that is both easy to understand and appealing to non professionals?
What are the main research directions and progress of immunotherapy at present?
How to regulate T cell metabolism to improve the effectiveness of immunotherapy?
Is there a specific bacterial resource that can be utilized within the tumor, and what is the possibility of these bacteria replacing mitochondrial function?
What is the role of specific microbial communities and bacteria in cancer research? Will they affect treatment, chemotherapy or other aspects?
What specific examples can illustrate the application of packaging modification technology?
What is the role of probiotics in tumor treatment and the necessity of expressing antigens?
What are the main reasons for CRS storm in CAR-T cell therapy?
Takeaways
We need to consider the feasibility of the project, that is, whether it can be completed within the time, energy, and resources of our undergraduate team. At the same time, we also need to pay attention to the uniqueness and differentiation of the topic, as well as whether it can be combined with practical problems and regional differences. We need to ensure that the selected topic is a small and specific problem that can be completed within our team's resources, while avoiding overly grand themes.
Yes, we suggest considering the relevance of the topic to local practical problems and choosing a topic that can solve practical problems. This way, the topic not only has scientific research value, but also has social impact.
To distinguish one's own topic from others', one can identify the differences between the topics. For example, if our goal is to treat tumors, we can focus on specific directions such as bacteria and microorganisms, and conduct research based on actual regional issues.
In the process of scientific research, the first step is to learn to use mainstream biomedical search engines (such as PubMed, Web of Science, etc.) and master basic literature search skills, such as using keywords for precise searches, understanding the conclusions and methods of different research papers, and analyzing the effectiveness of experimental design and data statistics. In addition, exchanging and discussing with experts in the field is also an important way to deepen understanding and improve scientific research level.
This involves translating complex professional knowledge into language that is easy for the general public to understand, and using vivid examples or metaphors to illustrate. For example, when explaining the principles of immunotherapy, the immune system can be likened to the human body's "police force", fighting cancer by stimulating and enhancing its function, rather than directly killing cancer cells. In addition, successful cases can be shared, such as two researchers from a certain school achieving significant clinical results through immunotherapy, to demonstrate the effectiveness and safety of this method.
At present, various methods of immunotherapy have been developed, such as PD-1 and PD-L1 based control therapy, as well as CAR-T cell therapy. Although these methods have achieved significant success, there are common issues of low response rates and limitations, such as only 20% of 100 patients receiving a certain drug being able to improve. At the same time, immunotherapy technology still faces many challenges in clinical application, such as how to ensure the safety and efficacy of treatment, and how to solve the problem of cell depletion.
In order to improve the effectiveness of immunotherapy, researchers have found that regulating the metabolism of T cells can reverse or slow down their functional decline. The specific approach is to regulate specific cytokines and triggering factors, especially signaling pathways related to T cell metabolism, such as the ITAM series. These regulatory measures can help T cells maintain effective function for a longer period of time, thereby enhancing the overall effectiveness of immunotherapy. In addition, T cell therapy using secreted factors has been explored, which has shown significant experimental effects in animal models and can improve response rates to 100%. Clinical trials are currently underway to verify its safety and effectiveness.
Some discussions may mention the use of bacteria to replace mitochondria for aerobic metabolism, that is, to maintain the energy supply of tumor cells through bacterial metabolism. However, this method has not been widely applied or fully implemented, and its specific effects are related to different types of tumors, requiring further research and confirmation.
Research has found that certain microbial communities may have an impact on different types and stages of cancer, and may have beneficial or harmful effects within the tumor. Although there is evidence to suggest the presence of bacteria within tumors, their specific mechanisms of action are not fully understood. However, current research has shown that bacteria do not affect other cellular functions in flow environments.
For example, by modifying genes to enable cells to secrete specific proteins (such as cytokines) and fixing a transmembrane technique on the cell membrane, sustained release of specific substances can be achieved, such as for drug delivery, to solve the problem of cytokines penetrating the tumor and spreading to other parts during tumor treatment.
Probiotics may play a role in activating immune cells in tumor treatment, but it is necessary to ensure that they can effectively present antigens to the immune system for recognition. However, relying solely on probiotics to express antigens may not be the best solution, and it is also necessary to consider whether probiotics will cause excessive reproduction and other issues. Therefore, when designing treatment plans, it is necessary to comprehensively weigh various factors, including but not limited to literature review, logical sorting, and team collaboration discussions.
The CRS storm is mainly caused by a large number of CAR-T cells entering the body, carrying killing signals that quickly activate the immune system, triggering a series of cytokine storms, leading to symptoms such as fever and muscle pain.
Interviewee: Qi Xie
Introduction
School of Life Sciences Biology Tumor Stem Cell and Tumor Microenvironment Laboratory View more: https://xieqi.lab.westlake.edu.cn/
Looking for
During the initial stages of our research, we planned to develop auxiliary probiotics to assist CAR-T, CAR-M, or CAR-NK cells in leveraging their targeted therapeutic advantages within the tumor microenvironment (TME). However, we needed expert guidance to overcome the challenges of simulating the complex TME in vitro. And the interaction between tumor stem cells and tumor microenvironment, as well as the improvement of tumor immunotherapy (CAR-T, CAR-NK, etc.), is currently one of his research directions
Question we asked
We are researching the production of bacterial expression antibodies that bind to TME as antigens and immune cells to alter the tumor microenvironment and enhance cancer treatment efficacy. Regarding CAR-T, CAR-NK, and CAR-M therapies, we would like to ask which one may be more suitable for our current topic and kindly request that you elaborate on the prominent advantages and potential disadvantages of each cell therapy.
In the tumor microenvironment (TME), which targets are suitable as bacterial expression products to enhance the efficacy of therapy?
If we choose NK cells as our research direction, which mechanism of action is more powerful or advantageous in practical applications compared to CAR mediated specific killing and antibody dependent cell-mediated cytotoxicity (ADCC) in terms of the killing effect of NK cells themselves?
Takeaways
Using CAR-T, CAR-NK, or CAR-M was not feasible due to existing challenges.
The TME is highly complex and contains various elements, making it very difficult to simulate in vitro.
NK cells naturally possess the ability to recognize tumors, so additional mechanisms may not be necessary.
Consequently, we shifted our focus toward bacterial-based therapy by engineering Salmonella to target and kill cancer cells.
Interviewee: Pengbo Cao
Introduction
School of Medicine School of Life Sciences Biology Lab of Bacterial Infectious Disease View more: https://www.thepclab.org/
Looking for
When we faced difficulties in choosing a Two-Component System (TCS) for signal transduction, particularly concerning the transmission of signals from the outer to the inner membrane. He focuses on analyzing key bacterial behaviors at the molecular level, such as RNA and proteins.
Question we asked
The typical structure of a CAR consists of an antigen-binding domain, a transmembrane domain, and an intracellular signaling domain. Our goal is to engineer these receptors into Gram-negative bacteria, which presents a significant challenge due to the large size of the transmembrane domain and the difficulty in transducing external recognition signals. We are considering modifying the Tol-Pal system to address this issue, but we are aware that this is a complex task. Therefore, we wanted to reach out to him for his expertise. Specifically, we need a system that enables recognition plus downstream signal transduction, which would ideally activate the transcription of certain plasmids.
Takeaways
Professor Cao suggested considering the Tol-Pal system for transducing signals from the outer to the inner membrane to activate gene expression. However, he pointed out the complexity of modifying the Tol-Pal system to integrate single-chain variable fragments (scFv) and downstream signaling. He recommended looking into other existing two-component systems and ensuring that the ligand or antigen can diffuse into the periplasm for recognition by the scFv.
Second Phase
Betta Research Report
Symposium Details
Date: 2024/06/25
Attendees: Betta, Westlake-CHINA
During the summer vacation, we visited Betta Pharmaceuticals, aiming to gain insights into its new drug development process and the current market landscape of oncology treatments. On the morning of June 25th, we arrived at Betta Pharmaceuticals, where the company's president guided us through a comprehensive tour and elaborated about their pharmaceuticals production processes.
The development of a new drug necessitates traversing three distinct phases: early exploratory research (3-6 years), clinical studies (6-8 years), and market launch (0.5-2 years). This endeavor is characterized by its long cycle, high investments, and inherent risks. According to the president of Betta Pharmaceuticals, it typically takes over a decade, costs more than a billion dollars, and boasts a success rate of less than one in ten. Thus, the pursuit of new drug development is an arduous endeavor.
Early Exploratory Research (3-6 Years)
It encompasses target selection, lead compound identification, optimization, and preclinical studies. It begins with pinpointing disease-related biological targets, followed by screening 5,000 to 10,000 compounds to identify potential candidates. These compounds are then optimized to enhance efficacy and minimize side effects. During the preclinical phase, approximately 200-300 promising compounds are selected through laboratory and animal testing that assess safety, pharmacokinetics, and pharmacodynamics. This phase is lengthy, costly, and fraught with risk, with a success rate hovering below 10%. The ultimate goal is to filter out candidates eligible for clinical trials.
Clinical Studies
Phase I
It encompass preliminary clinical pharmacology trials, human safety evaluation, and pharmacokinetics studies. They provide initial insights into the drug's safety profile in humans, its absorption, distribution, metabolism, drug- drug interactions, and tolerability alongside adverse reactions. This phase lays the foundation for safe medication use and informs the design of Phase II and III trials with preclinical data. Typically involving 20 to 100 healthy volunteers, Phase I marks the inception of human testing for new drugs.
Phase II
It represents a crucial stage in drug development, often employing randomized, double-blind, controlled trial designs to evaluate the efficacy and safety of candidate drugs in a larger patient population. Recruiting 100 to 500 patients for a 1- to 2-year trial, this phase generates invaluable data on efficacy, dose-response, safety, and potential adverse effects, crucial for advancing to Phase III and subsequent market authorization.
Phase III
It is pivotal in the new drug development process, featuring large- scale, multicenter, randomized controlled trials designed to further assess a drug's effectiveness and safety. Enrolling 1,000 to 5,000 patients, this phase not only validates the drug's efficacy in a broader population but also delves into dose-dependent effects and potential side effects, providing robust data for final regulatory approval. As an anticancer drug enters this crucial phase, it signifies that the culmination of countless researchers' efforts is poised to face the ultimate real-world test. Beyond the laboratory, brave cancer patients are the driving force of scientific progress, serving as beacons of hope for future generations.
Post-Marketing Surveillance (Phase IV)
It commences once the drug is launched. This phase, initiated by the drug-maker, focuses on studying the drug's efficacy and adverse reactions under widespread use, evaluating its benefits and risks in general or special populations, and optimizing dosing regimens. Key features of Phase IV trials include: 1) Typically, no control group is required, though small- scale randomized controlled trials may be conducted for specific indications or patient subsets as needed. 2) Enrollment exceeds 2,000 cases. 3) While open- label, the trial design adheres to Phase II standards, including eligibility, exclusion, and withdrawal criteria, as well as evaluation criteria for efficacy and adverse reactions. This phase is paramount to ensuring the drug's safety and efficacy in real-world applications.
Conclusion
The president of Betta Pharmaceuticals emphasized the importance of humanistic care throughout clinical trials, respecting patients' wishes and privacy while ensuring that they are fully informed of potential risks and benefits. During trials, research teams meticulously monitor participants' health, promptly adjusting treatment plans to safeguard their wellbeing. Each participant's journey is a profound testament to the meaning of life, narrating humanity's resilience in the face of adversity. Researchers, apart from pursuing scientific truths, must deeply recognize that behind every data point lies a living, breathing individual yearning for healing, understanding, and respect. Thus, Phase III trials transcend mere scientific milestones, evolving into heartwarming journeys of shared growth and strength. With this in mind, the Betta Pharmaceuticals president introduced us to mainstream oncology drugs in the Chinese market and their company's latest developments, which were invaluable insights, as they continually look to improve patient care and outcomes.
Dermatology Interview Report
Symposium Details
Meeting Date: 14:00-16:00 on July 16, 2024
Participants: iGEM Student Team from Westlake University, Dr. Zhong Jianbo Meeting Topic: Introduction and Discussion of Team Project
Project Background
We have devised a scheme for tumor therapy utilizing Salmonella bacteria. Through genetic modification, these bacteria are engineered to target tumor cells and release expression plasmids, thereby achieving therapeutic effects.
Project Content
Modification of Salmonella
Utilizing the VNP20009 strain to enhance tumor colonization and targeting efficiency.
Knocking out genes to disable motility and cell penetration capabilities while preserving the ability to recognize tumor cells.
Incorporating antibodies for targeted recognition.
Introducing two plasmids, one for expressing cytotoxic proteins and another for forming a biological switch, ensuring activity solely within tumor cells.
Treatment Protocol
Initially injecting modified Salmonella to colonize the surface of tumor cells.
Subsequently administering a second strain of Salmonella with penetration capabilities, facilitating entry into tumor cells alongside the cytotoxic strain.
The cytotoxic Salmonella lyses intracellularly, releasing plasmids, which trigger the expression of cytotoxic proteins in tumor cells, leading to apoptosis.
Safety Design
A biological switch ensures that cytotoxic proteins are expressed exclusively in tumor cells.
A population density control loop regulates the number of invading Salmonella to prevent overgrowth.
Special promoters control the lysis of cytotoxic Salmonella, preventing the expression of cytotoxic proteins in normal cells.
Discussion Points
Tumor Types: The project primarily focuses on melanoma but aims to expand to other skin tumors, such as basal cell carcinoma.
Safety: Dr. Zhong emphasized the paramount importance of safety, ensuring no harm to normal cells or complications.
Efficacy: Dr. Zhong raised concerns about tumor stemness, antigen escape, and bacterial delivery to tumors, highlighting areas requiring further research.
Clinical Application: Dr. Zhong discussed the current treatment landscape for melanoma, including surgery and immunotherapy, and suggested considering local treatment options, taking into account tumor count, differentiation, patient age, and regional factors.
Data Acquisition: Dr. Zhong shared insights on acquiring clinical data, advising the team to collaborate with hospitals for annotated data.
Future Prospects: Dr. Zhong believes the project holds significant potential and could potentially replace some traditional treatment methods.
Meeting Conclusion
The team's project is innovative and feasible but requires further refinement of experimental design and safety assessments.
Dr. Zhong's invaluable clinical experience and advice are crucial to the team's project.
The team will continue experimental research and actively seek collaborations with hospitals.
Additional Information
Dr. Zhong shared information on common dermatological diseases, including infectious, immune-mediated, and neoplastic conditions, and their treatments.
He introduced the application and significance of dermatoscopy, advocating for the team to explore AI's role in skin tumor recognition.
Dr. Zhong imparted knowledge on vitamin D supplementation and skin aging.
Summary
This meeting was a successful exchange, with the team gaining invaluable clinical insights and advice from Dr. Zhong, providing direction for subsequent research. The team remains committed to striving for excellence in the competition and advancing the clinical translation of their project.
Oncology Interview Report
Symposium Details
Date: July 16th-17th, 2024
Time: 13:30-15:30, July 17th
Venue: Hubin Campus of Hangzhou First People's Hospital, 261 Huansha Road, Hangzhou, Zhejiang
Participants: iGEM Student Team from Westlake University (Dingqi GU, Chenlu XUE, Fan Yang, Xinlin WANG, Yuhao WANG, Junbo QIAN, Weiyan CHENG, Yishan ZHOU), Dean Xin FANG, Directors Jingjing XIANG, Xinyu QIAN, Sumei CHEN, Kan WU, Yi WU, Xin FANG (President of Hangzhou First People’s Hospital)
Agenda
Understanding the Current Status of Melanoma and Breast Cancer Treatment
Application Prospects and Challenges of CART Therapy
R&D Plan for a Novel Anti-Cancer Drug Using Salmonella to Deliver BAX Plasmids to Cancer Cells
Discussion Points
Safety: Concerns about the drug's impact on cellular activity, potential adverse reactions, and collateral damage to normal cells were raised.
Efficacy: The ability to eliminate all cancer cells, including dormant ones, was discussed. Considerations included differential inhibition of primary and metastatic tumors, temporal differences, target internalization, mutation- induced unrecognizability, dose-response, and the complexity of tumor genetics.
Drug Resistance: The potential for the drug to induce resistance was a point of discussion.
Cost: Associated costs with drug development and production were considered.
Market Prospects: The drug's market competitiveness and the financial burden on patients were discussed.
Technical Advantages: The drug's technical advantages over existing anticancer drugs and its applicability to different tumor types were considered.
Symposium Focus
Bacterial Vector Penetration: The ability of bacterial vectors to penetrate and colonize tumor cells was discussed, with a focus on the advantages of anaerobic bacteria in the tumor microenvironment.
Safety and Side Effects: Doctors discussed potential side effects and immune reactions, especially with the use of bacterial vectors.
Delivery Method and Specificity: The discussion focused on delivery methods to the tumor site and ensuring treatment specificity to cancer cells.
Clinical Applications and Cost-Effectiveness: Exploration of treatment methods in clinical trials and cost management.
Challenges in Tumor Microenvironment: The complexity of the tumor microenvironment's impact on treatment efficacy was discussed.
Immune Evasion in CAR-T Therapy: Challenges with immune evasion and the exhaustion of immune suppression functions in CAR-T cell therapy were raised.
Optimization of Treatment Plans: Suggestions for optimizing treatment plans to enhance effectiveness and reduce side effects were made.
Regulatory and Ethical Concerns: Concerns about compliance with NMPA and NHC regulations and ethical aspects of the treatment were discussed.
Meeting Summary
The students gained valuable insights and planned to refine their project, specifically to the efficiency issue of the treatment, which foster the change from the previous two-bacteria system to the T-SAT method. The faculty encouraged the students, believing in their potential to develop an impactful anti- cancer drug.
Additional Information
Biomarkers: AFP in liver cancer, PSA in prostate cancer, and pathways like EGFR and TROP2 were mentioned.
Intertumoral Injection: Three patients died from cytokine storms in the case of brain gliomas.
Conclusion
The integrated oncology report highlights the importance of safety, efficacy, cost, and market prospects in the development of a novel anti-cancer drug. The symposium emphasized the need to address challenges in the tumor microenvironment and optimize treatment plans for enhanced patient outcomes.
Interaction with BNU-China Team
Symposium Details
Date: 2024/07/18
Attendees: BNU-CHINA, Westlake-CHINA
BNU Project
Background
Soft Robots: The new generation of robots, which are safer, more flexible, streamlined, and energy-efficient compared to traditional rigid robots.
Marine Exploration Applications: Discusses the application of soft robots in deep-sea exploration, featuring jellyfish and octopus robots.
Market Analysis: Presents the market distribution of soft robots across North America, Europe, and the Asia-Pacific region.
Potential Damage To Soft Robots In Marine Environments: Discusses the challenges soft robots may face in marine environments, such as limited lifespan, suboptimal recyclability, and unsustainability.
Existing Methods: Introduces current self-healing polymer methods, which have issues like high energy input and long repair times.
Design
Mussel Adhesive Protein: Studies the characteristics and bonding mechanism of mussel adhesive proteins, selecting Mfp5 protein with 30% DOPA content.
Co-expression System: Designs a co-expression system, including TyrVs (tyrosinase) , Mfp5 and Mfp6 proteins, and TRn (squid ring teeth protein).
Improvement of Circular RNA: Improves circular RNA by adding a downstream box (DB), ensuring the optimal length of the td exon, and adding a strong promoter (RBS).
Folding Prediction And Molecular Dynamics Simulation : Predicts and validates the stability and rationality of the designed sequences through a molecular modeling workflow.
Expectations
Production Process: Describes the production process from collection, purification to freeze-drying of protein powder.
Application: Discusses how to use freeze-dried protein powder and hexafluoroisopropanol (HFIP) to cast models and create soft layers.
Folding Prediction: Validates the designed sequences through molecular dynamics and free energy docking.
Model and Human Practices (HP)
HP Structure Overview: Introduces iGEM BTI's interactive learning, personal growth, and community building.
Current Achievements: Includes projects like seed art, straw hat design, herbal exploration, and children's medicine kit production.
Social Media Education: Promotes education through WeChat and Instagram.
Collaboration: Participates in the Yangtze River Conference and Synthetic Biology Conference.
Future Plans: Includes connecting with NAU-CHINA through email, city walk videos, and posters.
Goals
To connect NAU-CHINA with a broader world and promote exchange.
To engage more people in synthetic biology and promote educational equality.
To enhance public understanding of self-healing materials for soft robots.
Interaction with Fudan Team
Symposium Details
Date: 2024/08/27
Attendees: Fudan Team, Westlake-CHINA
Fudan Project
Three-Dimensional Gene Research and Applications
Addressed water pollution caused by divalent nickel ions.
Project is divided into three parts: enhancing absorption, expulsion, and transformation of internal accumulation.
In E. coli, the increased expression of NixA, a membrane protein, and introduction of metallothionein adsorbs and coordinates metal ions which mitigates cellular toxicity.
Models of E. coli and cyanobacteria were established, and MSD analysis was used to study the transport efficiency of divalent ions.
Discussed potential applications, aiming to purify wastewater during discharge.
Wastewater Treatment and Gene Repeat Sequence Research
Explored the functionality of repeat sequence engineering and studied how genomic repeat sequences aid in structural replication using imaging techniques.
Mentioned that cyanobacteria's photosynthesis can produce hydrogen, a well-established biohydrogen production technique.
Also discussed issues related to wastewater treatment and recycling.
Westlake Project
Progress in Targeted Cancer Therapy
Salmonella, a facultative anaerobic bacterium with potential for cancer therapy, was highlighted for its strong penetration of tumors and low inflammatory risk.
Developed a Salmonella strain carrying the BAX gene to induce apoptosis in cancer cells through the following steps:
Expression of HER2 antibody on the surface of Salmonella for recognition and attachment to cancer cells.
Transfer of a plasmid containing the BAX gene into Salmonella, which is expressed within cancer cells to induce apoptosis.
Designed a plasmid with PsseJ promoter and φx174E gene to ensure transcription only within cancer cells, inducing Salmonella lysis and release of the BAX gene-carrying plasmidS.
For safety, a self-lysis circuit was introduced to trigger autolysis when bacterial density is too high.
Laboratory Life and Project Progress Sharing
Discussed training models and data outcomes in the laboratory, as well as professional choices and issues related to studying abroad.
Mentioned a project from Zhejiang University with a different focus.
Addressed issues with P2 laboratory, and the safety phone and fire- retardant flags.
Also discussed the application and preparation for on stage talk and the method of presenting projects at venues.
Team Collaboration
Both parties became partners, took a group photo, and exchanged cultural and creative gifts as a memento.
Interaction with Shanghai Jiao Tong Team
Symposium Details
Date: 2024/08/27
Attendees: Shanghai Jiao Tong Team, Westlake-CHINA
Shanghai Jiao Tong Project
Humanitarian Care for Xeroderma Pigmentosum (XP)
Discussed a project on Xeroderma Pigmentosum, a genetic disorder where patients, like the protagonist in a popular film, can only be active at night due to extreme sensitivity to sunlight. The story highlights the need for awareness and care for XP patients, who typically show symptoms between six months to three years of age and often develop cancer by the age of 20. Currently, there is no cure for this condition.
Project Design and Implementation Strategy
The project aims to restore gene function to UV switches as a treatment. It involves combining UVR8 and VP64 genes, and COP1 with GAL4 genes, followed by linking XPC and RUP2 genes to a modified CMV promoter. The use of a P2A linker allows for independent translation of XPC and RUP2 genes. UVR8 forms a cytoplasmic homodimer in the absence of UV-B signals, but upon exposure, it forms an active monomer that enters the nucleus.
Human Practice
Developed a flowchart from patient symptoms to diagnosis and treatment progression based on interviews with doctors and patients. Analyzed local treatment structures, created a relationship map, and assessed the project's strengths and challenges. Focused on high- impact groups such as medical researchers and healthcare personnel, as well as low-impact groups like the World Health Organization and the Red Cross. Designed the project to meet safety and innovation standards, with specific measures outlined.
Westlake Project
Medical Ethics and Exploration of Genetic Disease Treatment
Discussed the requirement for ethical committee approval before pharmaceutical companies can go public, along with regulations from drug administrations and health commissions. Also addressed issues in genetic disease therapies, such as methods of drug administration and maintaining drug concentration. Introduced a new integrated track this year focusing on treatments for breast and melanoma cancer, planning to use Salmonella to deliver plasmids to cancer cells, inducing them to express the plasmid and self-destruct.
New Strategies for Targeted Tumor Treatment
Salmonella, as a facultative anaerobic bacterium, shows unique potential in anti-tumor therapy with its ability to penetrate deep into tumors and induce apoptosis without causing inflammation. We innovatively designed a therapy using Salmonella carrying the BAX gene: Salmonella is engineered to express HER2 antibodies on its surface for precise recognition and attachment to cancer cells; the introduced BAX gene plasmid is expressed within the bacteria, prompting cancer cell apoptosis. The PsseJ promoter and φx174E gene work in synergy to ensure bacterial lysis and release of the plasmids carrying BAX gene only within cancer cells, further promoting the apoptotic process. Additionally, a self-lysis circuit is designed to automatically lyse bacteria when their density is too high, controlling the risk of infection. This comprehensive strategy not only enhances the targeting and efficiency of treatment but also ensures the safety of the treatment process, opening new avenues for anti-tumor therapy.
Open Discussion
Discussed the differences between cancer cells and normal cells and how to distinguish them. Also mentioned some experimental details and a project animation that has an established script and is currently in production. Finally, discussed funding and equipment issues.
Meeting with Tongji University
Symposium Details
Date: 2024/08/28
Attendees: Tongji-CHINA, Westlake-CHINA
Tongji Project
Introduction
The project aims to develop an eco-friendly and sustainable wet adhesive for bio-nail art using composite hydrogels.
Key Focus Areas
Environmental Nail Art: Development of a novel bio-nail art product utilizing environmentally friendly materials to reduce the use of harmful chemicals in traditional nail products.
Health and Safety Concerns: Examination of the safety of nail products, including the detection of harmful chemicals in gel samples, the risks of UV exposure, and damage caused by nail gel removal processes.
Environmental Impact: Investigation of the environmental effects of nail product manufacturing, such as the release of harmful chemicals, soil and water contamination, and the disposal of chemical waste.
Sustainable Materials: Development of a sustainable adhesive layer using mussel foot protein and hydrogel, which exhibits excellent adhesion in wet environments and is safe and non-toxic.
Technical Research: Exploration of yeast in engineering as a model organism and the concept of compartmentalized production.
Algorithms and Software: Development of an assisted directed evolution model and a graph deep learning-based directed evolution support model to optimize protein targeting efficiency.
Human Practices: Conduct of background investigations, surveys, technical consultations, bio- art consultations, and exploration of commercialization.
Education and Publicity: Organization of educational activities, finger dances, university communications, cross-boundary exchanges, and gene music projects in the "Nonsense Lab."
Urban Applications: Discussion on the potential application of wet adhesives in urban settings as a sustainable biomaterial.
Conclusion
The project focuses on developing eco-friendly nail art products while addressing health, safety, environmental impact, sustainable materials, technical research, algorithm development, human practices, and educational outreach, aiming to promote environmental and health product innovation.
Interaction with ShanghaiTech Team
Symposium Details
Date: 2024/08/28
Attendees: ShanghaiTech-CHINA, Westlake-CHINA
ShanghaiTech Project
Background
Pruritus (Itching Issue): Itching is a widespread problem, and persistent itching can cause significant discomfort to people.
Staphylococcus aureus (S. Aureus): This is a common bacterium and a key topic in the field of skin health.
S. Aureus and Itching: Studies have shown that S. Aureus can directly activate itch-sensing neurons, thereby causing itching.
Project Design
Functional Validation: The project designed a natural compound detection method that translates itching into fluorescence.
V8 Protease Kinetics: Investigated the structure and dynamics of the V8 protease from S. Aureus.
E. coli Itch Sensor: Designed an E. coli-based itch sensor.
V8 Plasmid and Flip System: Utilized the Flip system and fluorescent protein reporter genes to detect protease activity.
FlipGFP System: Designed a FlipGFP-based system for detecting protease activity.
Anti-Itching Substances: Explored substances that can alleviate itching.
Wet Lab Design
Molecular Dynamics Simulation: Conducted molecular dynamics simulations of Flip GFP and Flip mCherry.
Computer-Aided Drug Screening: Performed computer-based drug screening.
E. coli Metabolic Analysis: Conducted a metabolic analysis of E. coli.
Human Practices and Education
Card Game: Designed an educational card game.
Minecraft Creation: Created educational content in Minecraft.