ABSTRACT

First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Dominika Agnieszka Rudzka is first author on ‘Migration through physical constraints is enabled by MAPK-induced cell softening via actin cytoskeleton re-organization’, published in JCS. Dominika conducted the research described in this article while a PhD student in Professor Michael Olson's lab at the Cancer Research UK Beatson Institute, Glasgow, UK. She is now a Senior Scientific Officer in the lab of Dr Heather McKinnon at the same institute, investigating cancer cell invasion and migration, and related drug discovery and protein translation.

Dominika Agnieszka Rudzka

How would you explain the main findings of your paper in lay terms?

Cancer cells are softer than the normal cells from which they are derived. Such a feature allows them to migrate/invade much more easily through the dense extracellular matrix surrounding them, and to subsequently reside and colonize distant organs. To identify factors contributing to increased cancer cell plasticity, we selected cells, from established cell lines, that were more efficient at migrating through narrow membrane micropores. What we found was that these pore-selected cells had reduced cell stiffness, had more disorganized actin cytoskeletons and reduced focal adhesion density. To reveal the underlying mechanism responsible for such features, we performed a transcriptomic analysis and found that the pore-selected cells had increased Ras/MAPK signaling output. We then blocked signaling through this pathway (by using a MEK inhibitor), and determined that the inhibitor treatment reversed the elasticity, cytoskeleton, focal adhesion and transcriptional changes.

Were there any specific challenges associated with this project? If so, how did you overcome them?

If I had to choose one specific challenge during my project, I would say it was the use of different microscopes and microscopic methods; for example, FRAP to measure membrane fluidity or TIRF to visualize actin organization. Before my PhD, I hadn't had much experience in this topic; therefore I found it occasionally difficult. To perform the experiments and the analysis correctly required lots of discussion with other scientists and experts in a particular field.

When doing the research, did you have a particular result or ‘Eureka’ moment that has stuck with you?

The eureka moment during my research occurred when I was looking at my pore-selected cells through the microscope after MEK inhibitor treatment to find out whether it had any impact on the actin cytoskeleton and focal density organization. That was a very striking moment when I noticed that the disorganized actin cytoskeleton in pore-selected cells reversed into organized actin filaments upon treatment. I think that was the most wonderful moment during my PhD research.

Why did you choose Journal of Cell Science for your paper?

We chose the Journal of Cell Science as it has got a very good reputation. Moreover, it allows us to reach a broad audience in the cell biology field. Therefore, we decided that it is a great place where we could publish our study.

Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?

During my research, my biggest mentor was my supervisor Professor Michael Olson. He always had time to discuss the obtained results and always gave me good suggestions on how to take the project forward. Moreover, he is a very collaborative scientist. Therefore, we were able to perform some experiments that were out of our area of expertise. Besides my supervisor, I could always count on other scientists within the group and PIs within the institute. They were always very happy to share their thoughts and ideas on my project.

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?

Since high school, I have always been interested in biological science, especially molecular biology. The idea that a single cell – the most basic micro unit of life – is able to perform processes that are extremely complicated, and that scientists are able to witness the world inside a single cell and study the causes of different diseases, such as cancer, has always been very fascinating for me and pushed me to study the cell ‘micro universe’ in more detail.

TIRF images of filamentous actin structure of pore-selected MDA MB 231 human breast cancer cells. Cells were treated with DMSO (A) or MEK inhibitor (B).

TIRF images of filamentous actin structure of pore-selected MDA MB 231 human breast cancer cells. Cells were treated with DMSO (A) or MEK inhibitor (B).

Who are your role models in science? Why?

I think that my role models in science are all women who juggle two different and very demanding jobs – family/home and academic research. I find it very inspiring.

What's next for you?

After finishing my PhD, I started working in the Drug Discovery Unit at the Beatson Institute. Working in the Drug Discovery Unit allows me to combine an industry-standard drug discovery job with high-quality academic research. The research in drug discovery is very multidisciplinary, allowing me to get to know topics and techniques from different areas of research. Moreover, it provides a more applied science opportunity compared to the more basic scientific work in academia.

Tell us something interesting about yourself that wouldn't be on your CV

I am very interested in healthy lifestyle and well-being and how to approach health difficulties in a more natural way. Also, I love salsa dancing.

Dominika Agnieszka Rudzka's contact details: Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK.

E-mail: d.rudzka@beatson.gla.ac.uk

Reference

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D. A.
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(
2019
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Migration through physical constraints is enabled by MAPK-induced cell softening via actin cytoskeleton re-organization
.
J. Cell Sci.
132
,
jcs224071
.