First person – Andria A. Lytridou

Andria A. Lytridou

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

The endoplasmic reticulum (ER) is the largest membranous organelle of eukaryotic cells and is implicated in several cellular processes. Maintenance of the ER, homeostasis (balance), is crucial for proper ER function. Disruption of ER homeostasis results in a condition known as ER stress, which leads to the activation of a cell survival mechanism known as the unfolded protein response (UPR). UPR activation influences a number of cellular processes aimed at restoring ER balance and supporting cell survival. Our study revealed that the response of skeletal muscle precursor cells (myoblasts) to ER stress involves the formation of large glycogen clusters in cells. Moreover, we have identified the protein that triggers the above ER stress-induced cellular response, the glycogen-binding protein starch binding domain-containing protein 1 (Stbd1), which is mainly found on the ER membrane. The results of our study demonstrate that activation of ER stress stimulates an increase in the protein levels of Stbd1 that is specifically required for the formation of glycogen clusters at the ER membrane. We have further addressed the biological significance of the above ER stress-induced cellular response and provide data suggesting that it supports cell survival during ER stress. Given that ER stress occurs physiologically during the process of myoblast differentiation to muscle fibres, the results of our work may have wider biological significance during myogenic differentiation.

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

In respect of the experimental part of the project, we had difficulty detecting the cleaved/activated form of caspase-3 (Casp-3) protein due to its low molecular weight and the detection of non-specific proteins with similar molecular weight by the antibody used. We solved this problem with the use of precast gradient gels, which enabled the separation of the protein band of interest (cleaved Casp-3) from the unspecific ones. However, I believe that the most difficult time during this work was when we received the comments of the reviewers on the first version of the manuscript. This was almost in parallel with the outbreak of the COVID-19 pandemic and, as in many countries in Europe, following initial movement restrictions, a nationwide lockdown was imposed a few weeks later in Cyprus. Access to the lab and facilities, as well as the purchase and dispatch of reagents required for additional experimental revisions, became a real challenge. I am very grateful to the JCS Editorial Office for granting an extension to the revision period upon our request for completing the revision of the manuscript.

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

As this project was focused on investigating the role of a largely uncharacterized protein, there were many ‘eureka’ moments during this work. But if I had to pick one, it would be the moment when we realized that expression of Stbd1 is absolutely required for the formation of the ER stress-induced glycogen-containing structures. Wow! This process must have biological significance, we thought. Then, we moved on and showed that the ability of myoblasts to respond to ER stress through this Stbd1-dependent process is associated with cell viability.

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

Journal of Cell Science is an internationally acknowledged journal publishing high-quality articles encompassing all aspects of cell biology with an Open Access option. Our work describes a cellular response of mouse myoblasts to ER stress and also uncovers molecular mechanistic details of this process that might apply to other cell types. The study therefore fits very well with the scope of the journal. Also, our team has previously published a paper in JCS, and the experience with the submission process, peer-review and communication with the Editorial Office was overall very positive. I am glad that my first published work has been professionally reviewed with transparency and accepted by JCS.

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

My PhD supervisor, Dr Petros P. Petrou, has been an essential contributor to my career, as under his supervision I have developed my critical thinking and laboratory skills to the utmost. He used the quote ‘The laboratory is no place for experimentation’, meaning that for a researcher to get the answer he looks for, he has to ask the right questions, study and design the proper experiments and interpret his results without bias. His excitement and commitment to our work were really inspiring (thank you!). In addition, my co-author Dr Anthi Demetriadou, who initiated this research project along with Dr Petros P. Petrou, played an important part in my PhD training as she was always happy to share her knowledge and expertise. Both of them encouraged me to pursue the PhD, and I am pleased that I have worked with them.

Who are your role models in science? Why?

I think it would be unfair to narrow down the list of role models in science to only the well-known researchers with a reputation. I admire scientists that have passion and commitment for their work, the ones that do not give up, even if nothing is working as expected. I appreciate my colleagues who face difficulties with courage and patience, and who start all over again to reach their goals. They are the ones who inspire me!

What's next for you?

In the near future, I will be writing up my thesis and defending my PhD work. After that, I would like to work as a postdoctoral researcher, to further develop as a scientist and use my current knowledge to address unanswered questions in my field of interest.

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

In my free time, I love going to the gym because it relieves all of my stress and boosts my confidence, especially after long, busy days in the lab. Also, I am always happy to party, dance and travel with my loved ones!