Developing Project

We focused on the hottest issue in recent society. Based on Google Trends and our interests, we choose medical care as the field of our research. Cancer, the most concerned area in medical field, attracted our attention. It is estimated that in 2014, the number of new cases of malignant tumors in the country was 3.804 million (2.11 million males and 1.69 million females), and an average of 7 people per minute was diagnosed with cancer (data from the National Cancer Center). According to the latest data released by the American Cancer Society in the "CA: A Cancer Journal for Clinicians" magazine, there will be 1,688,780 new cancer cases and 600,920 cancer deaths in the United States in 2017. Cancer is a global disease that threatens human health and is the second leading cause of death in the United States. Statistics show that there were 1,688,780 new cases in the United States in 2017, which means that 4,600 new cancer patients were added every day.

CAR-T full name Chimeric Antigen Receptor T-cell Immunotherapy, embedded and antigen receptor T cell immunotherapy, which combines antibodies against specific tumor antigens with CD3ζ, FcεRIγ in T cells and expresses them on patient T cells in vitro. Amplify, screen, and return to the patient in large quantities. The basic principle is to use the patient's own immune cells to clear cancer cells, which is a cell therapy, not a drug. CARs consist of intracellular signaling regions (such as CD3ζ and CD28), transmembrane regions, and extracellular antigen-binding regions of the T cell receptor (TCR). Recombinant CARs rely on the antigen but do not rely on the presentation of MHC, effectively avoiding the immune escape mechanism of MHC down-regulation

Cytokine storm refers to a variety of cytokines in body fluids such as TNF-α, IL-1, IL-6, IL-12, IFN-α, IFN-β, IFN-γ, MCP. The rapid and massive occurrence of -1 and IL-8 is an important cause of acute respiratory distress syndrome and multiple organ failure. It is a side effect of CAR-T immunotherapy. In order to relief cytokine storm, we develop a kind of engineered T cell, which can monitor and relief cytokine storm automatically

Improving Project

With the progress of our research projects, some experimental problems have come out. For solving these problems, we came to Shanghai Institute of Biological Sciences, Chinese Academy of Sciences with these questions. This activity is also playing an important role in our education & public engagement work.

In order to conduct an interview better, we have done a lot of preliminary work.

First, we browsed the website of the Shanghai Institute of Life Sciences of the Chinese Academy of Sciences to determine the list of researchers interviewed. Considering the theme of the event, we selected several researchers who have made great achievements in the field of cancer treatment.

Prof. Wang Hongyan: Immunocytes regulate new mechanisms of inflammation and inflammation-related diseases

Prof. Meng Feilong: How to suppress the occurrence of immune system tumors and important factors in various immunodeficiency diseases

Prof. Yang Chenghua: Using biochemical, molecular and cellular biology methods, combined with animal models and clinical specimens to study malignancy Molecular mechanism of tumorigenesis and development and research on the development and mechanism of targeted therapy for small molecule drugs

Prof. Ji Hongbin: molecular mechanism of lung cancer

Prof. Chen Jianfeng: Functional regulation of cell adhesion molecules in inflammation and cancer

In mid-July, we explained our interview intentions by mail and these researchers, and they agreed on the interview time.

Secondly, we thoroughly reviewed the relevant works and scientific research results of these researchers, and prepared the interviews in a targeted manner, and asked them questions about their research directions. In doing so, we can not only understand the most complete and authoritative information but also bring us closer to the respondents and make the interviews go successfully.

During the interview, we asked in detail about the respondents' questions about cancer, cancer treatment, new therapies, immunotherapy, and the rationality of the pricing of cancer treatments in the current market. The researchers made detailed answers. We have changed background of our project from weakening cytokine storm to monitoring EFGR targeted cancer by following recommendations came from interviewing of principal investigators working in Chinese Academy of Sciences. The reason why we change application field is that Synnotch cannot be used in the solution environment. Therefore, we change the target from different kinds of cytokines to EGFR, a kind of protein on the surface of the cell membrane, which can be bind with synthetic extracellular recognition domain of Synnotch effectively.

EGFR (epidermal growth factor receptor) is a protein that exists on the surface of both normal cells and cancer cells. EGFR is very important for cell growth and differentiation. When a cell's ligand binds to EGFR, EGFR will be activated, which will send a signal to the inside of the cell to control cell growth through the cell pathway.

However, compared with normal cells, many cancer cells have mutations that overexpress EGFR. When the ligand is attached to the mutated EGFR, this signal will remain “sent" all the time, resulting in uncontrolled cell growth and response. Different EGFR mutations lead to different kinds of cancers, such as non-small cell lung cancer, pancreatic cancer.

If we replace the upstream extracellular domain of our subject with EGFR antibodies, our design can accurately identify EGFR with different densities on the cell membrane surface, and judge whether the cells change according to the density of EGFR, thus realizing the recognition of cancer cells. Moreover, we can adjust the immune strength of the engineered immune cells and the threshold value of EGFR recognition by adjusting the promoter strength and the type of recombinase, so as to accurately distinguish normal cells with low density EGFR from cancerous cells with high density EGFR, protect normal cells to the maximum extent, and recognize and kill cancerous cells.

More project application details are shown in application page.

Application Research: Bigger Picture

As the work progresses, the understanding of the subject continues to deepen, we recognize that our system can convert the external fluctuation signals into simple 0 and 1 signals to realize the function of the analog-to-digital converter. Our system is very suitable for information processing. If we can convert the expression signals into electrical signals through light sensing elements in the future, we can realize the image displayed on our LOGO ——converting biological information into electronic information, make the machine biological and make biology engineering.

We have broadened our thinking, and the application of the topic is far more than the therapeutic field.

By replacing the identification object of the upstream system, the measurement of a certain substance can be realized. By adjusting the types of downstream promoters and recombinases, the system threshold can be adjusted. Then the system can not only detect the presence or absence of substances but also dynamically detect the concentration of the detected substances.

In the process of industrial production and environmental monitoring, by modifying the upstream channel, cells can identify their own products, metabolic wastes or miscellaneous bacteria, etc., and realize automatic adjustment of production according to external conditions or remind people to deal with corresponding situations.

We met with relevant practitioners in the above fields and showed them our project. We came to the Department of Oncology of the Third People's Hospital of Luoyang City, Luoyang City, Henan Province, and gave a simple interview with Dr. Guo Jianfeng, director of the Oncology Department. Dr. Guo first had a certain understanding of the iGEM topic, and then answered several questions about EGFR (record of this interview see attachments). We also interviewed several practitioners working in environmental protection related fields. They also gave us a detailed explanation of the current problem-solving solutions in related fields. In the future, we can replace T cells with any kind of cells, engineer them, and solve a series of social problems.