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. Vaishna Vamadevan is first author on ‘ Ubiquitin-assisted phase separation of dishevelled-2 promotes Wnt signalling’, published in JCS. Vaishna is a PhD student in the lab of Dr Subbareddy Maddika at Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana, India, investigating the role of ubiquitylation in regulating various cellular events.

Vaishna Vamadevan

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

The cellular environment is like a bustling city where many activities are happening at once in several places. Cells have specialized organelles, just as cities have buildings that are designed for specific activities. Outside of those structured buildings, it's common to see outdoor organized gatherings for events. Through a process known as phase separation, molecules inside cells can also assemble into ordered structures outside of organelles to meet special requirements. Our study reveals the importance of such a phase separation event occurring in cells during Wnt signalling, a pathway that is crucial for the development of all eukaryotic organisms. The pathway is often kept in check by breaking down a protein called β-catenin, which promotes the expression of Wnt target genes. In the present study, we discovered that dishevelled-2 (Dvl2), a protein involved in Wnt signalling, undergoes phase separation and coordinates the formation of proteins into a ‘destruction complex’, which protects β-catenin from degradation. Furthermore, we have demonstrated that another protein, WWP2, facilitates this phase separation of Dvl2 by attaching small molecules called ubiquitin to Dvl2.

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

One of the most difficult challenges we faced was a lack of immunofluorescent (IF) grade Dvl2 antibody. It was critical for us to test endogenous Dvl2 condensate formation in the physiological context of Wnt signalling. We tried several commercially available Dvl2 antibodies for our IF experiments, but none of them worked. We were unable to generate an in-house antibody due to the limited solubility of Dvl2 for in vitro purification. Finally, to address this, we created a stable cell line that expresses Dvl2 at near endogenous levels that forms condensates only when stimulated with a Wnt ligand.

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

This project had several fascinating findings that I was captivated by. Instead of believing an exciting result right away, I subjected it to rigorous testing for more confirmation. Sadly, by the time it was confirmed, I had already missed the rush of a eureka moment.

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

JCS is one of the most reputable journals in cell biology. Our study demonstrates the significance of Dvl2 phase separation in promoting Wnt signalling and its regulation through WWP2-mediated ubiquitylation. The study is unique in that it elucidates the mechanism of ubiquitin-assisted phase separation of a protein inside the cell, a topic of great interest in the field. We think that by publishing in JCS, our story will reach a larger group of cell biology enthusiasts.

Dvl2 condensates (green) sequestering GSK3β (red).

Dvl2 condensates (green) sequestering GSK3β (red).

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

Dr Subbareddy Maddika, my PhD advisor, has been an unwavering source of encouragement and support throughout my academic career. He is an incredible mentor who has always pushed me to think outside the box. The endless scientific discussions with him not only helped shape the project, but also shaped the future researcher in me. His trust in me and the freedom he gives me to work, inspired me to conduct independent research with great confidence.

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?

Science has excited me since my school days. When I initially learned that DNA has a double helix structure, I just thought of it as a piece of scientific knowledge. I was left wondering, though, how they discovered the structure without being able to see it with the naked eye. This shift in my curiosity from ‘what’ to ‘how’ made me realise that, behind the glory of every scientific discovery, there is a rigorous process of investigation and infallible interpretation of evidence to arrive at the correct conclusion. It triggered a great desire in me to become a scientist by inspiring me to believe that scientific study is both intriguing and challenging. The few research projects I conducted for my bachelor's and master's programmes helped me to grow even more passionate about pursuing a career in science.

Who are your role models in science? Why?

I feel that every modest contribution made to science has its own impact. The known and unknown individuals who contributed to all of the current scientific advancements have motivated me to continue in science.

What's next for you?

I'm searching for a post-doctoral position as I approach the completion of my PhD.

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

I enjoy taking part in or listening to debates about sociopolitical issues. I love reading every review and evaluation of a film that is available after watching it.

Vaishna Vamadevan's contact details: Centre for DNA Fingerprinting and Diagnostics, Inner Ring Road, Uppal, Hyderabad, Telangana, India.


Ubiquitin-assisted phase separation of dishevelled-2 promotes Wnt signalling
J. Cell Sci.