ABSTRACT
First Person is a series of interviews with the first authors of a selection of papers published in Biology Open, helping researchers promote themselves alongside their papers. Yuka Terada is first author on ‘ Intracellular dynamics of ubiquitin-like 3 visualized using an inducible fluorescent timer expression system’, published in BiO. Yuka is a Master's student in the lab of Natsumi Ageta-Ishihara at Toho University, Japan, investigating a novel post-translational modification factor, ubiquitin-like 3 (UBL3)'s physiological function.
Yuka Terada
Describe your scientific journey and your current research focus
I have been interested in science since childhood, and when I studied neurodegenerative diseases as an undergraduate at Toho University, I became interested in the principles of brain homeostasis and neuroplasticity. As an undergraduate, I conducted spatiotemporal analysis of the transport pathway of the novel post-translational modifier UBL3 and its substrates to multivesicular bodies (MVBs)/late endosomes using super-resolution live imaging. Currently, I am focusing on the brain, where UBL3 is highly expressed, and exploring its physiological function.
How would you explain the main finding of your paper?
Small extracellular vesicles (sEVs) are nano-sized vesicles secreted by almost all cell types, including cancer cells and nerve cells. sEVs contain proteins and mediate cell-to-cell communication. Additionally, the transmission of malignant proteins via sEVs is known to be involved in cancer metastasis and neurodegenerative diseases.
In a previous report, our research group discovered a novel post-translational modification factor UBL3, and found that UBL3 is localised to MVBs. Furthermore, we found that approximately 60% of all proteins transported to sEVs are UBL3-dependent, and that targets of UBL3 modification include proteins involved in cancer metastasis and neurodegenerative diseases. However, it was completely unknown when and where UBL3 associates with its target protein and is transported to MVBs within cells.
In this study, we constructed a system in which UBL3 was fused with a timer fluorescent protein that changes color from blue to red over time. We found that UBL3 is diffused in the cytoplasm after synthesis, accumulates on the plasma membrane and MVBs over time, and eventually predominates in MVBs. Furthermore, by super-resolution microscopy, UBL3 was found to be associated with one of its substrates, α-tubulin cytoskeleton, in the cytosol, and this complex was subsequently transported to MVBs.
What are the potential implications of this finding for your field of research?
In the future, new therapeutic strategies based on intracellular dynamics can be developed by visualising when and where proteins involved in cancer metastasis and neurodegenerative diseases, which are targets of UBL3 modification, associate with UBL3 and are incorporated into MVBs.
Association of a post-translational modification factor, UBL3 and α-tubulin, its substrate, in the cytosol and transport to MVBs. Super-resolution time-lapse images to track the bright spot of α-tubulin (blue) colocalised with UBL3 (green) and CD63 (a marker for MVBs, magenta).
Association of a post-translational modification factor, UBL3 and α-tubulin, its substrate, in the cytosol and transport to MVBs. Super-resolution time-lapse images to track the bright spot of α-tubulin (blue) colocalised with UBL3 (green) and CD63 (a marker for MVBs, magenta).
Which part of this research project was the most rewarding?
The most rewarding part of this research project was visualising UBL3 and one of its substrates, α-tubulin (the target of UBL3 modification), using super-resolution live imaging, and clarifying their intracellular dynamics. Before starting this research, I lacked the skills to operate a super-resolution microscope. However, I was determined to observe the movements of UBL3 and its substrates, and through repeated trial and error, I was finally able to capture their dynamics within seconds.
…I feel like I am constantly learning and growing as a person.
What do you enjoy most about being an early-career researcher?
I enjoy taking on the challenge of acquiring new knowledge and technology, and breaking into unknown fields. By working on unexplored fields and unsolved problems, I feel that my discoveries and insights may have a major impact on the future of science. Another big attraction is that I can try out flexible ideas and novel approaches, and I feel like I am constantly learning and growing as a person.
What piece of advice would you give to the next generation of researchers?
Don't be afraid of failure; take on the challenge! In the research process, there are many unexpected results and things that don't go as planned. I believe that learning from failure is the driving force behind generating new ideas and perspectives.
What's next for you?
I would like to continue my research into the physiological functions of UBL3. Regardless of the career path I choose in the future, I hope to maintain my interest in biomolecular science and continue making discoveries that contribute to society.
Yuka Terada's contact details: Department of Biomolecular Science, Faculty of Science, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
E-mail: [email protected]
