Inspiration
[1] https://cebp.aacrjournals.org/content/28/10/1563
Schabath, M. B., & Cote, M. L. (2019, October 1). Cancer progress and priorities: Lung Cancer. Cancer Epidemiology, Biomarkers & Prevention. Retrieved October 21, 2021, from https://cebp.aacrjournals.org/content/28/10/1563.
[2] https://www.who.int/news-room/fact-sheets/detail/cancer
World Health Organization. (n.d.). Cancer. World Health Organization. Retrieved October 21, 2021, from https://www.who.int/news-room/fact-sheets/detail/cancer.
We came across the idea of using VOCs while looking through previous iGEM projects. In 2017, Team Bilkent-UNAMBG created a project called DiagNOSE Cancer in which they used VOCs (volatile organic compounds) as biosensors as a noninvasive approach for early cancer detection. The Bilkent-UNAMBG team focused their research on VOCs in the most common types of cancer: lung, breast, colorectal and prostate. We decided to further their research, focusing on lung cancer. Lung cancer is also the leading cause of cancer death with more than 150,000 fatalities each year [2]. Additionally, only 16% of lung cancer tumors are discovered when it is localized, during which time there is a 56% chance of survival. 57% of lung cancer tumors are discovered when it is distant. At this time, the survival rate is only 5% [1]. Because of the low rate of early detection and high rate of mortality during later phases of the cancer, early detection is key to survival of cancer patients. The combination of past iGEM projects and statistics of lung cancer mortality lead us to further research noninvasive techniques for the early detection of lung cancer.
Synthetic Biology Application
Our detection method for lung cancer is a useful application of synthetic biology since we’re identifying volatile organic compounds (VOCs) present in lung cancer cells. Due to the presence of VOCs in lung cancer cells, the best way for the early detection of lung cancer would be to identify those VOCs. To be able to do this, we would need to design a detection system using E. coli bacteria to detect those VOCs in a person’s breath. These E. coli detection systems would use highly specific regulatory promoters that are dependent on the presence of VOCs to then induce the gene expression of a reporter gene, which will indicate the presence of lung cancer in the patient. Since E. coli is a living organism, it’s able to induce the expression of reporter genes, which is why we’re using the K-12 strain of E. coli in our project. Each VOC induces the expression of one reporter gene and the amount of reporter gene produced by each promoter indicates whether the VOC is upregulated or downregulated, which then indicates if someone has lung cancer. Therefore, the promoter needs to be highly specific for the amount of reporter gene to accurately reflect the amount of VOCs indicative of lung cancer, which would ensure an accurate diagnosis. An example of a reporter gene, and the one that we will be using, is GFP (green fluorescent protein), which would use its fluorescence to show scientists or medical professionals the presence of a certain protein or biomarker in the body. This biological system will be accompanied by a machine learning algorithm, which will use the quantification of the reporter gene expression. This quantification will be compared against baseline VOC levels in healthy patients, indicating whether or not a person has lung cancer.
COVID-19 Impact
Due to the current state of the pandemic, our 2021 iGEM project had to be completely virtual, similar to our 2020 iGEM project.
To start off, we explored the biggest positive of a completely virtual project. Being virtual meant that we had more options to connect with a plethora of people. Through our virtual connections, we were able to find lung cancer patients and lung cancer survivors through Instagram hashtags, as well as reach out to them through the platform. Through Instagram, we were able to interview patients from across the country at the utmost convenience of both ends. We also used our virtual platform to create and send out a survey to see how much the general public knew about lung cancer. After seeing the commonly missed questions on our survey, we were able to virtually create awareness and mythbusters posts surrounding lung cancer. Finally, our virtual project allowed us to meet with professionals through Zoom, like Dr. Mark Fuster from the American Lung Association. Through meetings like these, we were able to gain more insight into the practicality of our project.
With the positives came many negatives. We did not have access to a lab this year, which prevented us from doing lab work. This also made it so our project was entirely theoretical with no lab data to back up our constructs and parts. We also did not receive any help from our school, as well had to hold our team meetings virtually.