First person – Dikaia Tsagkari Free

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. Dikaia Tsagkari is first author on ‘ NHR-85 modulates mitochondrial and lipid homeostasis to protect against α-synuclein aggregation in C. elegans’, published in JCS. Dikaia is a PhD student in the lab of Nektarios Tavernarakis at Institute of Molecular Biology and Biotechnology of the Foundation for Research and Technology Hellas (IMBB-FORTH), Crete, Greece, investigating the role of systemic metabolism in neuronal health and disease.

Dikaia Tsagkari

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

Our bodies must maintain and regulate fat and energy metabolism to function properly. These processes are also quite important for our brain, as they contribute to healthy nerve cells. A transcription factor called PPARδ plays a key role in the regulation of metabolism and protects neurons from inflammation and degeneration, but its precise mechanism of action remains unknown. Thus, we took advantage of the nematode worm Caenorhabditis elegans to characterise the functional orthologue of human PPARδ, a nuclear hormone receptor called NHR-85, and elucidate its role in a model of Parkinson's disease (PD), a neurodegenerative condition. We found that NHR-85 regulates both fat and energy metabolism by affecting lipid droplets and mitochondria. Finally, we discovered that NHR-85 prevents aggregation of α-synuclein, a pathological feature of PD, probably through its role in mitochondrial quality control.

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

I think the most challenging part was the conceptualization of the specific project. Initially, we screened various nuclear hormone receptors in lipid droplets and mitochondria. We then discovered that NHR-85 loss of function caused a similar cell phenotype to PPARδ loss of function and that, according to the Alliance of Genome Resources, NHR-85 is the putative orthologue of PPARδ in C. elegans.

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

I was initially surprised that, on day one of adulthood in worms treated with nhr-85 RNAi, there was no difference in mitophagy associated with downregulation of nhr-85, especially given that we had previously observed significant changes in mitochondrial characteristics like membrane potential, morphology and mass. However, when we later investigated the effect of NHR-85 on mitophagy during aging, we discovered remarkable differences. It was at that point that I realized not everything is as straightforward as it may seem at first, especially in biology where all the processes are complex and intertwined.

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

Journal of Cell Science is a well-regarded peer-reviewed scientific journal in the field of cell biology. It publishes high-quality research articles on a wide range of topics related to cell biology, including molecular mechanisms, so we thought that our research topic fit perfectly.

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

Professor Nektarios Tavernarakis has been an incredible mentor throughout my journey, and he is the one who gave me the opportunity to begin my PhD. He also encouraged me to explore and discover my own research interests, which has been the driving force behind my continued passion for this field. Additionally, Maria Markaki, the second author on this paper, has been an invaluable mentor, both professionally and personally. Her guidance helped me stay focused, maintain a positive mindset and channel my enthusiasm, especially during times when I was overwhelmed by a multitude of ideas.

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?

During my last year of high school, my passion for biology began to blossom thanks to my incredible biology teacher, whose enthusiasm for the subject was contagious and inspired us all. During my undergraduate and postgraduate studies, I had the privilege of meeting inspiring professors and working under the guidance of Dr Jenny Fraser, Dr Dimitris Koutsioulis and finally with Dr Oscar Kuipers and Dr Amalia Dolga. These mentors have all played a significant role in shaping my journey and I believe it is people like them − who encourage young scientists to believe in themselves and their ideas − that help keep us motivated in the competitive world of science.

Who are your role models in science? Why?

My role models are incredible women who conduct groundbreaking research with passion while advocating for diversity and equality in the field. Their dedication and commitment inspire me and drive my own journey in science.

What's next for you?

I am preparing to defend my PhD soon and after that I am eager to continue my career as a postdoc, focusing on research in neuronal lipid metabolism. I am open to opportunities worldwide, where I can connect with and learn from new experts in the field.

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

Outside of the lab, my favorite hobby is contemporary dance. Additionally, having had the opportunity to pursue my PhD on the beautiful island of Crete, I also enjoy spending time at the beach, hiking and immersing myself in nature.