Team:ASIJ TOKYO/Results
RESULTS TEMPLATE
What is CRC?
Colorectal cancer (CRC), or colon/bowel cancer, is a common form of cancer that most frequently develops starting with polyps. In 2014, an estimated 1.3 million people lived with colon and rectum cancer in the United States. In fact, about 1 in 20 men and women are expected to have colon cancer at some point in their life. CRC is caused by the APC gene, or activating mutation in β-catenin, which results in the accumulation of β-catenin and subsequent complex formation with TCF/LEF transcription factors. Excessive β-catenin can interact with TCF to activate the transcription of proliferative genes, such as c-Myc and cyclin D1, in the colon.
Project Motivations
After speaking to Minako Abe, an immunologist, we became aware of the immense prevalence and impact--especially in Japan--of colorectal cancer. In Japan alone, in 2015, there were almost 50,000 deaths from colorectal cancer, marking a sudden, sharp spike in the number of young adults that were diagnosed with this cancer. Finding out that two faculty members at our school were survivors of this disease further cemented our belief in the importance of addressing it at its root. The issue is especially prevalent in Japan mostly because the younger generation is not fully aware on how common colorectal cancer is becoming and because they are not checking up on their bodies as frequently as they should be. This motivated us to not limit our project on only addressing early detection of CRC, but also raising awareness.
Figure 1: This is an inactive Wnt pathway with no mutated genes. Here, β-catenin is degraded appropriately and does not activate transcription of Wnt genes.
Figure 2: LiCl activates canonical Wnt signaling by inhibiting GSK3β-mediated phosphorylation of β-catenin. The inhibition of GSK3β activity prevents β-catenin degradation in the ubiquitin dependent proteasome pathway and leads β-catenin to enter the nucleus and interact with LEF/TCF family proteins to activate Wnt target genes. Without Wnt signalling, LKB1 serves as a binding partner for APC, recruits the APC/β-catenin destruction complex to the membrane, and inhibits Wnt signaling activity.
How did we do it?
Our goal was to create a biosensor that would be able to diagnose CRC at an earlier stage and have it fit for a home-kit where use would be accessible and convenient. To do so, we looked upstream fill in. The activation of the Wnt pathway inhibits the degradation of beta-catenin, a protein that triggers the mutation of oncogenes and tumor suppressor genes. Building off of a rapamycin induced split-luciferase system characterized by the 2015 Peking iGEM team, our construct consists of a promoter reporter system that looks at two downstream products, C-myc and COX-2. As for community outreach, we wanted to take advantage of the fact that we live in the most metropolitan area in Japan. We did so by carrying out our project mainly in Harajuku, which is one of the most popular areas in Tokyo. As ASIJ is also central to many international communities, we’ve also promoted our project at family events held at ASIJ, as well as through our virtual pre-medical club where we were able to interact with schools around the globe.
