Megan Konrath ’20
"Inter-strand Crosslinking of DNA by Novel Rhodium Complexes"
Major: Biochemistry
Hometown: Allentown, PA
Project Advisor: Dr. Shari Dunham
Briefly describe your project.
DNA, in biological processes such as cell division, transcription, and translation, needs to “unzip” (or come apart) in order to be processed. Interstrand cross-links covalently bond to DNA and link the two strands together, therefore inhibiting these processes. If the DNA in a cell cannot replicate or be processed, that cell cannot divide or code for a protein or other genes, ultimately leading to apoptosis, or programmed cell death. Cisplatin is a widely used anti-cancer drug, but it has many serious side effects (such as vomiting, diarrhea, hair loss, dry mouth, dehydration, loss in ability to taste food, etc.). Another downfall to cisplatin is that tumors are able to develop a resistance to the drug, therefore inhibiting the effectiveness of cisplatin as an anti-cancer drug. Our research during SOAR focuses on exploring novel dirhodium complexes pictured here. They contain 2 rhodium atoms (metal atoms) in their core, and their bridging groups are either trifluoroacetate (TFA) or acetate (OAc). The one rhodium atom will attach itself to a part of one strand and the other will either attach itself to the other strand, the same one, or to no strand at all. Over the summer, I reacted a fluorescent 39-bp DNA probe with a variety of novel rhodium compounds, screened these reactions for formation of interstrand cross-links, and determined if there is a correlation between the nature of the 4 bridging groups around the rhodium core and the DNA interstrand crosslinking efficiency.
Describe the origin of your project.
I was interested in doing some sort of cancer research, as I am a cancer survivor, and Dr. Shari came to me with this project and asked me if I’d be interested in working on it.
What’s the best part about working with your faculty mentor? What valuable insights have they brought to your project?
I loved working with my mentor because I was able to bounce off ideas with her and she encouraged me to try new things over the course of SOAR. She helped me to realize that even though I believed experiments ‘failed’, they instead provided helpful insight that allowed us to get more accurate data and find out what did not work.
What has been your biggest obstacle so far?
Our double stranded DNA was not fully double stranded – there was some unannealed top and bottom strands in the duplex solution. We are still trying to figure this out.
What has been your biggest takeaway from this experience?
Even when the experiments do not produce the outcome you expected/wanted, they did not fail – they just taught me something else.
What was the result of your project?
We did see interstrand crosslinks with the DNA reactions with Rh 0:4 (Rh2(TFA)4), but we were unable to quantitate the percent interstrand crosslinks because we did not have full duplex in our reactions to begin with.
In your own words, how do you feel about being awarded this opportunity? Why should other students take advantage of the SOAR program at ɫɫ University?
I am so thankful to have been able to participate in SOAR and do research in the lab. This has allowed me to get more practice in the lab, become a lab TA, and come up with an Honors Project. This experience will have a lasting imprint on me as one of the best summers of my life. If I had not been sick during the Landmark Conference, I would have been able to present my work in front of students and faculty from other colleges. For the reasons I mentioned above, I would recommend SOAR to other students at ɫɫ University and urge them to take advantage of this opportunity.
Now that SOAR is over, do you plan to expand upon your research? If so, how?
Yes. I am doing an honors project with Dr T and Dr. Shari, expanding the interstrand crosslinking research to how the rhodium compound solutions enter HeLa cells and effectively kill them.
Have you, or do you plan to present this research outside the SOAR presentations?
I wanted to present at the Landmark Conference, but I was unable to. I have continued some of my SOAR project this semester as an honors project, so I will be presenting during the poster presentations in the spring semester.