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. Anna Dowbaj is co-first author on ‘ An optogenetic method for interrogating YAP1 and TAZ nuclear–cytoplasmic shuttling’, published in JCS. Anna conducted the work described in this article while a PhD student in the lab of Erik Sahai at the Francis Crick Institute, London, UK. She is now a postdoc in the lab of Meritxell Huch at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Dresden, Germany, investigating the role of the stem cell niche in liver regeneration.
Anna Dowbaj
How would you explain the main findings of your paper in lay terms?
In our paper we report the development of a tool that allows us to control nucleocytoplasmic shuttling using light. We couple microscopy to mathematical modelling with an easy-to-use graphical user interface app, and using this we can derive the rates of protein shuttling in and out of the nucleus. In other words, we can influence the amount of protein available to shuttle between the cellular compartments with light, and by tagging your favorite protein with fluorescent probes and coupling the outcome to mathematical equations, we can watch where it goes in quantitative terms. We demonstrate proof of principle using our favorite proteins, YAP1 and TAZ, which are downstream effectors of the Hippo signaling pathway, but we hope the cell biology community can use this tool for other shuttling proteins. Importantly, this tool allows visualization of two proteins at the same time, which might be quite interesting when comparing different components of the same signaling pathway.
Were there any specific challenges associated with this project? If so, how did you overcome them?
Originally, we expected this tool to allow us to control YAP1-driven transcription. However, as we went along with development of the tool, we realized it is much more suited to investigating nucleocytoplasmic shuttling, which was both unexpected and exciting, as this is broadly applicable to other proteins.
When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?
I guess there have been a couple of eureka moments. The first moment that really stood out for me was when I first saw the optogenetic tool ‘working’ on a confocal microscope, which was still quite early in my PhD. I saw the dissociation of my fluorescent fusion protein from the mitochondria upon blue light illumination, and then it returned after I stopped the illumination – that was very rewarding and exciting. The second moment was at Janelia Research Campus at the end of my PhD when I saw our tool working in 3D. The increase in resolution and the detail we could see was incredible.
The optogenetic tool in 3D – as imaged using a lattice light-sheet microscope. Blue, nuclei; magenta, mitochondria; green, YAP1 optogenetic tool.
Why did you choose Journal of Cell Science for your paper?
We chose JCS because of its high-quality cell biology publications and commitment to data integrity. I personally also really enjoy the beautiful pictures in many of the publications.
Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?
Professor Erik Sahai, who was my PhD supervisor, has been the biggest influence on my scientific career to date. In addition to excellent scientific guidance throughout my time in his lab, he also taught me how to be calm when things don't go as planned.
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 attended a high school with a strong focus on biology and chemistry. The majority of my classmates went on to pursue medicine, but I felt that medicine was not for me – I was always more curious about how all biology works. After completing an undergraduate degree in molecular genetics at the University of Edinburgh and working in a lab, I was sure that science was the path for me – you can never be bored, as there is always something new and each day in the lab is different. Each biological question is like a problem waiting to be solved.
“…you can never be bored [with science], as there is always something new and each day in the lab is different.”
Who are your role models in science? Why?
Being Polish, Marie Skłodowska-Curie has always inspired me. I find it incredible that she mastered both chemistry and physics, a true interdisciplinarian, while being a woman during a challenging time in history.
What's next for you?
I would like to continue on the academic career track – fingers crossed it works out!
Tell us something interesting about yourself that wouldn't be on your CV
I love animals, and if I could afford it, I would open a rescue farm or stables. For the moment, I've just got a cat – she is very funny and cute. I like spending time with her and looking up new fun toys to get for her.
