Team:Worldshaper-Wuhan/Human Practices

Collaborations

Hp

IHP

Human Practice

Background story

Breast is one of the specific gifts to the women, playing the functions in feeding the offspring and depicting the graceful curve of their bodies. However, as the “first killer” to women, breast cancer threats the health of the women greatly. We are so sorry about that fact when we bethink of the passing of whose mother or daughter occurs every day (the fact that mothers and daughters passing away every day is devastating). From here, we derived our first inspiration. Recently, the news of Dr. Beth Levine’s passing carried a great weight of sorrow to us. Ms Li, our team PI, worked with Dr. Levine at the Autophagy Center of UT southwestern Medical center. Ms. Li told us a lot about Dr. Levine. Her outstanding contribution to the field of autophagy, her dedication and hard work to scientific research have deeply infected us. Moreover, her struggle with breast cancer inspires us to a greater extent. Therefore, we decided to focus on breast cancer. We developed our understanding of the public's awareness of breast cancer through questionnaires and street interviews, the current situation of breast cancer treatment through expert interviews and the latest technology through visits to relevant enterprise.

Questionnaire

Objective

Firstly, the questionnaire was released to find out general public’s understanding of breast cancer. Respondents were required to mark their degree of understanding about breast cancer themselves and answer questions about common knowledge of breast cancer, such as the age of high incidence of breast cancer and potential factors that lead to breast cancer. In addition, this questionnaire was designed to popularize essential knowledge about breast cancer. This objective is achieved by providing correct answers to the questions. Facts about breast cancer that needed attention were directly listed in the questions, and participants only need to check whether they know about the knowledge instead of providing an answer. By doing so, participants were able to absorb the knowledge that they previously lacked. Last but not least, we would like to evoke (bring) people’s attention to breast cancer. We informed every participant the importance of semiannual health examination for breast cancer early diagnose and treatment, and encourage them to have a healthy lifestyle to prevent breast cancer.

Result analysis

The first question, “how much do you know about breast cancer”, at the beginning of the questionnaire intends to mark the degree of public awareness about breast cancer by “know well” “have heard of” and “no idea”. Among the 761 respondents, about 84% of them marked their degree of understanding as “have heard of”. Only 13% of respondents answered “know well”, and 2% answered “no idea”. It indicates that the majority of the society relatively lacks the knowledge about breast cancer. (It indicates that the public awareness on breast cancer is limited) This conclusion also accords (aligns) with the following results. For example, 46.5% of respondents did not know that early-stage breast cancer patients show no typical symptoms, and 55.9% of them is unaware that women between ages 50 and 54 are highly risky for breast cancer.

Fig.1.1 Q: How familiar are you with breast cancer? A:Blue: no idea 2.1%; Yellow: know well 13.93%; Green: have heard of 83.97%

Fig.1.2 Q: Do you know that early-stage breast cancer patients show no typical symptoms? Blue: yes, I do 53.63%; Green: no, I do not 46.65%.

Fig.1.3 Q: Do you know that women between 50 and 54 years old are highly risky for breast cancer? Blue: yes, I do 44.15%; Green: no I do not 55.85%

The target audiences were divided into groups by age and gender. According to the survey result, females tend to be more concerned with breast cancer. Only 0.86% of the female respondents replied that they had never heard of breast cancer, while that number for male is 6.1%. In addition, teenagers (age 13 to 17) are less willing to go to the hospital if they show breast cancer symptoms than people from other age groups. An average of 85% of respondents from other age groups (over 69; 45-69; 18-45) are willing to go to the hospital, while that number for teenagers is only 67%. There are multiple reasons behind this result. According to our survey, one of the main reasons is that teenagers are afraid to tell their parents about their physical abnormalities. Other reasons include parents’ indifference, intense study life and the lack of financial support. Furthermore, in terms of public support for our project, 63% of respondents opted for “support”, others expressed their concerns since they lack understanding of synthetic biology.

Fig.1.4 Q:What do you think of the practice of using synthetic biology to improve the accuracy of breast cancer treatment?Support 63.6%; No confidence, but hope for progress 8.41%; Do not support 0.26%; Have no idea about synthetic biology 26.4%; Don not care 0.79%.

Conclusion

From the survey result, we conclude that public education about breast cancer is greatly needed since the majority of the general public lack common knowledge about breast cancer and synthetic biology. This provided support for our public education implementation. The support rate of 63.6% of our project indicates that our project is meaningful for the general public.

Street interview

In August 2020, our team conducted a street reasearch activities in Wuhan. On August 12, 2020, we conducted a Street interview on Chuhe Han Street in Wuhan. People were asked simple questions about breast cancer and their views on using synthetic biology to diagnose and treat breast cancer. During the interview, we also happened to interview one patient with breast hyperplasia, she told us about her experience and gave us encouragement. Through street interview, we realized that people generally lack common knowledge about breast cancer and synthetic biology. So we gave them information about breast cancer and our plan to use synthetic biology to diagnose and treat breast cancer, which was supported and encouraged by most of them.

Photo1/2: Street interview on Han street in Wuhan

Interview with experts

Potential assessment----Application universality of our project

Experts who engaged in our interview provided great support for our project. Our project can be easily covered in health screening, therefore increasing the possibility for breast cancer early diagnosis and treatment. From the interview with Dr. Li Rong, Director of Thyroid and Breast Surgery in Wuhan No. 6Hospital, Member of Breast Cancer Expert Committee of Hubei Clinical Oncology Society (ESCO), who has been engaging in clinical and research work of breast diseases for more than 20 years., we learned that even if the detection methods for breast cancer are already mature enough, for most of the time, breast cancer patients examined and confirmed by the hospital are already in the middle or advanced stage. There are multiple reasons behind this phenomenon. First of all, early-stage patients show no typical symptoms. Without the ability of self-examination, it is hard for patients to identify early-stage breast cancer and visit hospital for comprehensive examination. Furthermore, some health screening process does not include breast cancer detection. According to Dr Song (oncology) and professor Pei (breast surgery) from......, the early diagnosis methods include molybdenum target X-ray and color Doppler ultrasound. These methods are usually combined with nuclear inspection, since any of them is unable to ensure 100% accuracy. However, taking into consider the cost and complexity of color ultrasound and X-ray examination, these methods may not be included in some health screening process. However, according to our proposed implementation (CTC/Cell-Free Protein Synthesis System), breast cancer detection can be done by simple blood test, a process that is involved in nearly all health examination packages. “If this project can be applied, the rate of breast cancer early diagnosis can greatly increase.” said Dr Li.

Photo3/4: Interview with experts

Generality of basic mechanism

According to the interview with Dr Song (oncology) and professor pei (breast surgery), causes of breast cancer have something in common with the causes of other malignancies, as well as some common problems of genetic changes at the molecular level. From the communication with professor Sarah Chavez, the Senior Scientist in Community Outreach and Engagement for the Division of Public Health Sciences and Siteman Cancer Center, we learned that ncRNA XIST plays a vital role in many kinds of malignant tumors, and the regulation function of miRNA can be decisive in all kinds of tumors. Professor Chavez also recognized some similarities of our project and some projects related to miRNAs in her lab. These similarities include the basic idea of identifying and visualizing miRNAs. Our basic mechanism of visualizing and identifying miRNAs is transfecting them into cells where they previously didn’t exist is a generic method that may be applied to other cancer biology research projects. In addition, our study of XIST may also provide some inspirations for future research.

Field Reasearch in Kindstar Global Company

During the August, our team members visited Kindstar Global Company, a high-end biomedical diagnosis company. With the guidance of the professor Zhou, we visited the staff's work and some high-end instruments, and learned about the achievements and partners of Kindstar around the world. Through this visit, we learned that our project may develop into one of the most high-end scientific research fields in the future, and could help more people to understand breast cancer better and get access to medical resources, so as to establish further protection of people's health.

Photo 5/6: visit to Kindstar Global Company

Summary

Through questionnaires and street interviews, we learned that: the majority of the general public lacks some common knowledge about breast cancer and synthetic biology, so public education is greatly needed; most people, including one patient we interviewed, expressed support for our research design. Through expert interviews and our visits to biomedical diagnosis company, we learned about the necessity of our project and we are also proud to receive affirmation and support from several experts in related fields. Through our human practice, we are confident that our project is of great significance to the public.

Safety in Human Practices

In year 2020, the coronavirus outbreak has influenced many aspects of our life: Schools are closing, sports leagues have been canceled, and many people have been asked to work from home. The COVID-19 pandemic is also an unprecedented challenge for iGEM competition this year, especially when we carried out human practice work. A large part of our public engagement program was done by interviewing passers-by on the street. Similarly, we had face-to-face conversations with several experts working in the field of breast cancer or synthetic Biology. In both cases, wearing a mask was undoubtedly indispensable for safety concerns. We were also careful to maintain distance with one another and avoid direct contact with door handles and elevator handrails. We also obtained the consent of the interviewees before taking photos and videos.

1. Breast is one of the specific gifts to women, but breast cancer kills around 42690 people this year (2020), and 99% of them are women. 2. The news that Dr. Beth Levine, a famous American microbiologist and our beloved role model, passed away carried a great weight of sorrow to us because of the breast cancer. Her long struggle with breast cancer inspired us to study breast cancer. 3. Cancer patients’ struggles during the Covid-19 also concerned us deeply. As the situation improved, we want to make our contribution to the cancer community.

Therefore, we decided to focus on breast cancer.

1. Through talking with our advisor Dr. Zhou Rui, professor at School of Medicine, Wuhan University. We have acquired some relevant knowledge: IncRNA is closely related to the diagnosis and treatment of breast cancer.

As a result, we had the idea of using IncRNA to detect breast cancer.

1. From the survey result, we conclude that public education about breast cancer and synthetic biology is greatly needed since the majority of the general public lack common knowledge about breast cancer and synthetic biology.

We decided to take common knowledge of breast cancer and synthetic biology together as our public education content.

1. According to previous studies, several lncRNAs, including XIST, NEAT1, GAS5, MAL1-AS, SNHG16, were selected for further investigation.

After our modeling analysis, both XIST and NEAT met our requirement.

1. After getting a preliminary idea on the selection of IncRNAs, we decided to ask experts for advice on its feasibility. Disappointingly, the first expert we interviewed, Dr. Chen from the Department of Urology, Peking University School of Medicine, told us that the current diagnosis of breast cancer is very mature. It is of little significance to study ordinary breast cancer diagnosis. It is recommended that we narrow the scope, such as the metastasis of breast cancer or a certain type of patients, such as breast cancer patients during pregnancy.

After the interview we decided to refine our direction to breast cancer metastasis, because one of our two candidate lncRNA, XIST, is related to breast cancer metastasis.

1. Disappointingly, during the virtual meetup with our friend teams, we noticed that the XIST expression level had decreased before breast cancer metastasis occurred. As a result, we were unable to detect breast cancer metastasis using XIST.

Soon, we got rid of the sad mood. We decided to interview more experts and look for new directions.

1. Dr. Song and Pei: According to Dr. Song (oncology) and Professor Pei (breast surgery) from the First Affiliated Hospital of Zhengzhou University, the early diagnosis methods include molybdenum target X-ray and color Doppler ultrasound. These methods are usually combined with nuclear inspection since any of them is unable to ensure 100% accuracy. However, taking into consideration that the cost and complexity of color ultrasound and X-ray examination, these methods may not be included in some health screening process. 2. Dr Li: Director of Thyroid and Breast Surgery in Wuhan No. 6 Hospital, Member of Breast Cancer Expert Committee of Hubei Clinical Oncology Society (ESCO), who has been engaging in clinical and research work of breast diseases for more than 20 years. we learned that even if the detection methods for breast cancer are already mature enough, for most of the time, breast cancer patients examined and confirmed by the hospital are already in the middle or advanced stage of cancer. There are multiple reasons for this phenomenon. The primary reason is that early-stage patients show no typical symptoms. Without the ability of self-examination, it is hard for patients to identify early-stage breast cancer and visit the hospital for a comprehensive examination. Furthermore, some health screening process does not include breast cancer detection. 3. Advisor Dr. Zhou:lncRNAs could act as sponges to complete miRNAs, participating in various biological processes. miRNA Sponges contain complementary binding sites to a miRNA of interest, which inhibits miRNA activity. miR-155 is one of the miRNAs of XIST, and a growing number of studies highlights its role in drug resistance development. According to previous studies, miR-155 is closely related to the proliferation, invasion and metastasis of breast cancer. Therefore, it may be used to detect breast cancer or evaluate the effects of radiotherapy and chemotherapy.

The interview with the experts from oncology and breast surgery reinvigorated our interest in breast cancer diagnosis. After the discussion, we have reached the following conclusions: 1. We decided to shift the focus of our project features to personalized treatment. Given the fact that lncRNA could act as a miRNA sponge, we designed the sequence that could bind tomiR-155 based on XIST sequence. 2.The goal of our proposed implementation is to develop a new method that breast cancer detection can be done by a simple blood test, which could be included in nearly all health examination packages.

1. Dr. Sarah Chavez is a Senior Scientist in Community Outreach and Engagement for the Division of Public Health Sciences and Siteman Cancer Center, who has a family history of breast cancer. Thanks to our advisor, Huang Yiming, for helping us contact her. We were very honored to be able to show her the results of our project, and engaged in an in-depth discussion with her. She suggested some future research plans for our project. Firstly, we learned about a new kind of microprobe. It can be used to quantify the expression of miRNAs, improving the accuracy of our experiment. In addition, if the experiment conditions permit, we can conduct a mice experiment in which we knocked down the mi-RNAs of mice. Then, comparing to the control group condition, we would be able to determine and explore the relationship between the patient’s resistance and mi-RNA 155. 2. In addition, NJU-China (Nanjing University team) suggested us during the virtual meetup that we can look at more than one microRNA to improve the accuracy of breast cancer diagnosis.

Following the suggestion of Dr. Chavez, our future work will emphasize on the patients’ drug resistance with miRNA 155. NJU-China also pointed to a new direction for us: exploration of more microRNA options for better breast cancer diagnosis.