The following post contains a reflection on my year-long project.
To Recap...
I am investigating how the addition of the antibiotic Novobiocin Sodium Salt to a PARP inhibitor treatment of RIN-m Rat Beta Cells with Insulinoma impacts the health of the cell culture. PARP inhibitors causing fatal oxidative stress in a subset of tumor cells with deficiencies in DNA repair. PARP inhibitor resistance in tumor cells is an emerging problem, and the inhibition of the DNA repair by Novobiocin Sodium Salt is a potential pathway for reversing resistance. This research will contribute to the academic conversation around increasing PARP inhibitor efficacy in tumorigenic cells, in order to improve their cancer treatment potential.
Content Reflection
I have learned so much about the microbiological pathways behind DNA repair and mutation through this project. My research was not limited to the PARP1 and theta-mediated microhomology-mediated end joining pathways—PI3K/Akt/mTOR, RAS, and other signaling proteins were defined and explained along the way. These pathways (cellular signaling pathways, called signal cascades) are being heavily investigated in relation to cancer. One researcher that I spoke with at a research symposium, Ian Fleming, told me about his group's work with the RAS pathway and P13K signaling in relation to the cause of cancer. These pathways are the next step to targeted cancer treatment, and I will be able to take the knowledge I acquired this year and take it to the Cancer Institute at University of Wisconsin-Madison. Additionally, my research has opened up the opportunity for a position in the CU Anschutz Cancer Institute next summer, where I should be able to continue my PARP inhibitor research.
Picture 1: This picture shows the inside of the CO2 incubator mid-experiment.
Picture 2: This picture details the researcher sleeping on the job ;).
Picture 3: This image depicts the researcher running hemocytometer assays during data collection.
Picture 4: This image depicts the researcher (far left) presenting a portion of his work at the DCSD School Board meeting.
Product Reflection
The process of writing my academic paper was incredibly productive, as it caused me to reinvestigate the literature surrounding PARP inhibitors and Novobiocin that was published during my project. The news article that I based my initial inspiration (July, 2021) for my project off of, published by the National Cancer Institute about an ongoing study at the Dana-Farber Cancer Institute, really undersold the scope of the ongoing research. The team at the Dana-Farber Cancer Institute published their final paper about their work with Olaparib, Novobiocin, and PARP-inhibitor-resistant ovarian cancer in late 2021, right about the time I began my experimental process. Reading through their paper was fascinating, because their section on in-vitro tissue culture and treatment had very similar methodology to my study. Their results were also significant, and they went a step further. They grew a patient-derived xenograft (PDX) of ovarian cancer in a mouse model and observed complete tumor reduction within 28 days of implementing the Olaparib and Novobiocin treatment schedule. This was very significant in comparison to Olaparib on its own, and suggests the efficacy of Olaparib and Novobiocin in certain types of ovarian cancer in addition to my demonstration on pancreatic cancer. This study was fascinating, but it also provides more context for the research I was able to achieve as a high schooler. The combination of the presentation and the paper impressed my expert mentor enough to offer me a spot at a research symposium in CU Anschutz, so I will be presenting my research to other PARP inhibitor researchers in late May, 2022. This applies to my future learning by exposing me to more current PARP inhibitor (and related) research during the symposium process.
Process Reflection
My experience in biotechnological research has not been limited to this process, and I will post a separate post reflecting on the lessons that I have learned through experience external to this class. However, from this class specifically, I learned how far I am able to go if I put my mind to something. I started with an idea—I wanted to work with cells. That gradually narrowed to cancer cells, and then even more to Olaparib and Novobiocin. Even then, however, there was so much more to understand. Literature reviews are one of the most time consuming processes I have ever encountered, due to the process of defining all of the terms in the field that you are not familiar with. However, I kept going through the process. Eventually, I put together methodology that resembled professional research design in my chosen field and achieved statistical significance with tumor cells that had previously been overlooked for PARP inhibitor research. There is no understating how important this process was for my overall career development—it increased my knowledge of targeted cancer treatment research, created connections and opportunities that were previously unavailable, and aided in the creation of my ever-expanding lab-skill repertoire. These skills will aid me in my chosen career path until I retire—it truly was a one-of-a-kind opportunity that the AP Research program sent my way.
Picture 5: This picture depicts RIN-m cells growing in a plate, the core of the project.
Sources
All factual information in this post not directly obtained through my own experiment was taken directly from my AP Research Paper, which can be accessed here.
All visuals were taken/created by the researcher.