ABSTRACT
First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping researchers promote themselves alongside their papers. Marina Bleiler is first author on ‘ Incorporation of 53BP1 into phase-separated bodies in cancer cells during aberrant mitosis’, published in JCS. Marina is a PhD student in the lab of Charles Giardina at Department of Molecular and Cell Biology, University of Connecticut, USA, investigating molecular mechanisms impacting survival of mitotically stressed cancer cells.
Marina Bleiler
How would you explain the main findings of your paper in lay terms?
Normal cells have multiple mechanisms for maintaining DNA integrity to ensure that they divide with intact DNA. Defects in cancer cells allow them to bypass this surveillance and proceed into mitosis with broken DNA. However, repairing DNA during mitosis can result in spurious chromosome end-joining, which would jeopardize cancer cell survival. We find that cancer cells sequester a critical DNA repair protein, 53BP1, away from DNA during mitosis to prevent random chromosome end-joining and cell death. This finding suggests that cancer cells have a peculiar requirement to suppress DNA repair during mitosis. This may be a potential weakness of cancer cells amenable for therapeutic targeting.
Were there any specific challenges associated with this project? If so, how did you overcome them?
Timing was sometimes challenging. Cells do not always agree on your schedule. You treat cells with a drug or some other agent in the morning and expect them to be ready for the following procedure the next afternoon. But they grow a little slower and their density is still lower than expected. So, you must push the next step into evening or maybe night. What did I do? I planned for a ‘rainy day’, kept my eye on cells, and complied with cell requirements when necessary.
When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?
We were trying to determine whether 53BP1 bodies in mitotically stressed colon cancer cells colocalize with other types of bodies. We co-stained cells for 53BP1 and coilin, a protein scaffolding Cajal bodies. Looking through the microscope, I thought that both 53BP1 bodies and Cajal bodies were just like polka dots, beautifully round. Then I recalled that a spherical appearance is a characteristic of phase separation, and that Cajal bodies are thought to be a liquid–liquid phase separated (LLPS) compartment. I then realized that 53BP1 mitotic stress bodies might also be formed through LLPS. We were able to support this suggestion with additional experiments.
Why did you choose Journal of Cell Science for your paper?
It was not a difficult choice. The Journal of Cell Science is a highly reputable peer-reviewed journal with established scientific standards. I have read many helpful papers in the Journal of Cell Science and found them professional, innovative and very clearly presented. We are excited about the possibility to share our findings with other scientists and are honored to become a part of the journal's long and influential history.
STED image shows 53BP1 mitotic stress bodies (grey) on mitotic chromatin (red) in a colon cancer cell.
Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?
My major adviser Dr Charles Giardina is a terrific mentor. Not all my experiments worked at first. His message was always, “stay positive; at the least, do not be negative”. The friendly atmosphere and collaborative environment that he maintains in our lab helped enormously.
What motivated you to pursue a career in science, and what have been the most interesting moments on the path that led you to where you are now?
I think it all started when I was a child at my first aquarium. I was fascinated by the different world. I made scrap books about different fish species and their habitats. I tried to breed fish. I dug through our local library for books on fish genetics, which were still rare in Soviet Russia after the long period of the suppression of genetic science. Though my career started with geochemistry, and included working in accounting, I wanted to come back to life sciences. Studying Biology here in the USA has opened for me new horizons.
What's next for you?
My Dissertation defense is coming soon. I will stay open for any kind of job related to my field.
Tell us something interesting about yourself that wouldn't be on your CV
Gardening sounds boring to some people, but I believe there are plenty of gardening enthusiasts who share my passion. Gardening here in north-eastern Connecticut is challenging due to cold winters, spring frosts and rocky soils. Indeed, over the years my husband, who is also an avid gardener, and I removed so many rocks from our garden that there is now a rock pile on the side of our yard that is taller than us. On the rewarding side, we have an established garden with many kinds of vegetables, berries and fruits. Quinces and fresh carrots taste delicious in winter!
Marina Bleiler's contact details: Department of Molecular and Cell Biology, University of Connecticut, 91 North Eagleville Road, U-3125, Storrs, CT 06269, USA.
E-mail: marina.bleiler@uconn.edu
