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. Lucie Wolf is first author on ‘ EVI/WLS function is regulated by ubiquitylation and linked to ER-associated degradation by ERLIN2’, published in JCS. Lucie works in the lab of Michael Boutros at German Cancer Research Center (DKFZ), Heidelberg, Germany, investigating the many regulatory layers of cellular communication. She is now a postdoctoral researcher, but was a PhD student when the manuscript was submitted.
How would you explain the main findings of your paper in lay terms?
I like to think of the endoplasmic reticulum (ER) as the post office or packaging center in a cell. It prepares all kinds of cargo to be sent to its respective locations, which can be inside or outside the cell. We analysed the protein EVI (also known as WLS; here denoted EVI/WLS), which can be seen as a box that is available in the ER to be packed with so-called WNTs, proteins that are important for cell–cell communication. WNTs can only be sent with the help of EVI/WLS, and the two proteins are very important during embryonal development and also for tissue maintenance in adults. It seems as if cells like to have a good amount of EVI/WLS in stock, in case WNTs need to be send out rapidly. However, if there are no WNTs to be sent, EVI/WLS is recycled, and its parts can be used to build other cellular components (as an unused cardboard box might be recycled). How does the cell know which protein to recycle? In our study, we investigated the molecular stickers, and the labelling machine cells use to mark EVI/WLS within the ER for recycling. In this way, we could add a lot of molecular details and novel interaction partners to this little understood mechanism. Surprisingly, EVI/WLS carries a lot of different marks, which makes us think that they might be functionally even more important than ‘just’ for initiating recycling.
Were there any specific challenges associated with this project? If so, how did you overcome them?
I started this project very late during my PhD, because my initial project did not advance as expected. I had never worked on post-translational modifications before and suddenly there was a completely new field of research for me to explore, which was both challenging and exciting. Luckily, colleagues and collaborators helped us to get an overview of the ubiquitin research, the available tools and the relevant questions in the field.
When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?
In our paper, we analysed how certain enzymes modify our target protein EVI/WLS with ubiquitin. However, when we first tried to validate the candidates we had discovered in a screen, none of them had an effect. The bands on our western blots that showed ubiquitylation on EVI/WLS all looked more or less the same. Other treatments that should remove ubiquitylation from EVI/WLS also did not show any effects in our assays, which was worrying and confusing. One day while explaining the method to a student, I suddenly noticed that the data did make sense, if we assumed that EVI/WLS could be ubiquitylated at several sites. In this case, smaller effects of a single missing type of modification are masked by other remaining modifications on the target protein. We then used more refined techniques looking specifically at the modifications we were interested in and lo and behold – there was the phenotype!
Why did you choose Journal of Cell Science for your paper?
We felt that JCS would be best suited to reach researchers from both areas of research that the manuscript combines (Wnt signalling and the ubiquitin-proteasome system). It was also important to us that the journal has a strong focus on research integrity and the adherence to scientific standards.
Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?
Post-translational modifications in general, and ubiquitylation in particular, are not the main focus of our lab. Therefore, I am thankful to the many extremely supportive researchers in the ubiquitin field that I met at conferences or other meetings who took the time to discuss my findings with me (I would like to mention Thomas Sommer and Ron Kopito in particular, but the list goes on and on). This really advanced the project significantly and helped me to settle into this new area of research.
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 loved biology and chemistry in school, and I was always curious to solve riddles. My parents are not academics and some people might perceive this as a disadvantage for going to university or when pursuing a career in science. I personally never felt this way, both because of the continuous support from my family but also because of the many inspiring and helpful people I have met in school, during my studies and later as a PhD candidate.
Who are your role models in science? Why?
The postdoc who supervised my master's thesis, Dr Frédéric Chevessier-Tünnesen. He taught me a lot about the scientific process in general but also the importance of collaborations and scientific integrity. Now, I try to be as inspiring and supportive as he was towards me towards the people I supervise.
What's next for you?
I am now a ‘bridging postdoc’ in the lab of my PhD supervisor and have started to apply for postdoc positions in academia.
Tell us something interesting about yourself that wouldn't be on your CV
I love to craft presents for friends. Currently I am working on a ‘Hitchhiker's Guide to the Galaxy’ themed towel dispenser box (to be used in case of unexpected interstellar travel).
Lucie Wolf's contact details: German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany