Supervisor: Roseline Godbout
Project: Understanding how DDX1 gene levels in neuroblastoma affect resistance to treatment
Bachelor of Science with Honors in Cell Biology
Why did you choose this program?
Cell biology is one of the most versatile yet holistic programs at the University of Alberta! A background in cell biology equips you with the fundamentals for numerous biomedical disciplines, because cells are the core building blocks of life.
What did you get to work on throughout your studentship?
My favourite technique that I learned over the course of my studentship was the soft agar colony formation assay—a technique used to evaluate cellular transformation. This assay is unique in that the cells grow in suspension, and serves as a way of selecting for growth of cancer cells. I was also involved with tissue culture, treatment of cells with chemotherapy drugs and scanning microscopy.
What's been the best part of your experience so far?
The most rewarding part of doing research comes from taking a step back and looking at the big picture. Realizing that you are contributing to findings that can have a positive impact on the medical community is what makes the summer studentship worthwhile. On a lighter note, the Godbout Lab potlucks are amazing!
What interested you in the summer studentship program?
I am a two-time recipient of the WCHRI Summer Studentship. Last summer I had the experience of performing my own personal project in a field of interest to me. As I uncovered more findings over the course of my project, my curiosity was piqued and I wanted to keep asking questions and discovering using the scientific method.
What has the support from WCHRI and the Stollery Children's Hospital Foundation meant to you?
I am extremely grateful to the Stollery Children's Hospital Foundation for supporting my project over the last two years. As someone who is relatively new to research, this support gave me confidence that my project had the potential to make a significant impact upon the medical community.
Neuroblastoma (NB) is responsible for 15% of pediatric cancer deaths. While patient survival is high for low and intermediate-risk patients, over 60% of children diagnosed with high-risk NB do not survive past the age of five. High-risk in NB is often associated with amplification (increased copies) of a cancer-causing gene called MYCN. DEAD box proteins are involved in all cellular functions related to RNA, and hence play a significant role in cell survival.
Previous research undertaken by the Godbout lab indicates that the DEAD Box 1 (DDX1) gene is amplified along with the MYCN gene in about 50% of high-risk NB. The goal of this research project is to investigate the relationship between DDX1 expression levels and NB cell survival. Over the past year, we have compared the survival of NB cells treated with two chemotherapy drugs used in the clinic for the treatment of NB patients: doxorubicin and vincristine. We used NB cells that have MYCN amplification, and NB cells that have both MYCN and DDX1 amplification to examine the effect of DDX1 overexpression on NB cell survival. We also used an experimental approach called RNA-interference to investigate if knockdown of DDX1 (resulting in reduced levels of DDX1) played a role in NB cell survival. DDX1-knockdown in MYCN-amplified cell lines reduced NB cell survival in cells treated with doxorubicin, but no effect was observed with vincristine treatment. We will be continuing these experiments by examining the effects of DDX1-knockdown on NB cell survival in DDX1 and MYCN-amplified cell lines. I will examine additional chemotherapy drugs, such as etoposide and bleomycin.
As part of my summer research, I will also examine the effects of DDX1 expression level on DNA double-stranded break repair via immunostaining with markers used to detect these breaks and their repair mechanism. Through this research, we will gain an understanding of how NB cells become resistant to treatment, which is critical for the development of more effective treatments for children with high-risk NB.