First person – Yongli Zhang and Xuecheng Li Free

Yongli Zhang

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

Y.Z. and X.L.: Cilia are prominent organelles that extend from the cell surface, resembling antennas. Their structural core is composed of microtubules, which are exceptionally stable. In contrast, cytoplasmic microtubules are characterized by dynamic instability. What underlies this fundamental difference? We propose that microtubule-associated proteins within the lumen, known as SAXO proteins, play a crucial role in regulating microtubule stability. This concept can be compared to the Canton Tower, which stands over 600 m tall – a structure that relies not only on its outer frame but also on a complex internal network for support. Similarly, our research shows that the loss of multiple SAXO proteins disrupts the stability of the ciliary axoneme. This highlights the functional redundancy of SAXO proteins; while the loss of individual components might not immediately compromise structural integrity, cumulative loss can lead to significant destabilization. As for a tower building, the gradual accumulation of deficits could ultimately have catastrophic effects on the overall structure.

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

Y.Z.: One major challenge in this project was the lack of efficient gene-editing tools in Chlamydomonas, which initially prevented our ability to systematic investigate SAXO proteins, microtubule-stabilizing proteins that had long been of interest to us. Early studies relied on random mutagenesis to occasional obtain SAXO mutants, limiting our ability to analyze their functions comprehensively. Realizing this bottleneck, we developed an optimized gene-editing method for Chlamydomonas, which we published in The Plant Journal in 2024. With this tool in hand, we resumed the SAXO project and successfully generated a series of single and multiple mutants, ultimately revealing their roles in microtubule stabilization.

X.L.: The other major challenge we faced was the phenotypic analysis of various SAXO protein knockout mutants. Initially, when we obtained single mutants for four genes, we found that the singular deletion of each of them did not affect ciliary length, which was a significant setback to our confidence. However, after conducting a thorough literature review and discussing with Prof. Pan, we hypothesized that these proteins might exhibit functional redundancy. As a result, we began constructing double mutants, yet the results still showed no apparent changes. Fortunately, we persevered and proceeded to generate triple and quadruple mutants, which ultimately revealed the crucial role of SAXO proteins in maintaining ciliary length stability.

Xuecheng Li

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

Y.Z. and X.L.: We selected Journal of Cell Science because our study aligns with its focus on basic and mechanistic insights into cell structure and function. Our research investigates the roles of SAXO proteins in cilia, which are microtubule-based organelles essential for cell motility and signaling, using Chlamydomonas as a model. By integrating genetic, biochemical and proteomic approaches, we reveal the redundant functions of SAXO proteins in regulating ciliary length, assembly and axonemal microtubule stability, as well as their role in tubulin turnover. These findings fill a key gap in understanding the physiological roles of SAXO proteins and offer novel insights into ciliary biology, making JCS an appropriate and impactful venue for presenting our work.

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

Y.Z.: Professor Junmin Pan has been a profoundly influential mentor in my life, far beyond his role as a laboratory supervisor. In addition to offering rigorous scientific training, he often shared thoughtful advice on life, character, and how to navigate challenges – lessons I didn't fully grasp at the time but have come to deeply appreciate since graduation. What made his guidance especially meaningful was his genuine passion for science and his ability to connect with students. He celebrated my successes with sincere excitement, and during times of repeated failure, he never hesitated to offer encouragement and practical suggestions. One of his unique qualities was his talent for explaining complex scientific concepts through vivid, everyday analogies. This not only helped me understand difficult ideas but also shaped the way I perceive and approach science. His mentorship has left a lasting impact on both my scientific thinking and personal growth.

X.L.: I would like to express my heartfelt gratitude to my Ph.D. advisor, Prof. Junmin Pan, who is also the corresponding author of this paper on SAXO research. He has provided invaluable support and guidance throughout my research journey, fostering academic thinking, cultivating good habits, designing research projects, conducting literature reviews and encouraging us to attend academic conferences and engage in scholarly exchanges. Moreover, he has shown genuine concern for our personal development, consistently motivating us to achieve greater success in scientific research. This is one of the key reasons I chose to pursue my postdoctoral research under his mentorship.

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?

Y.Z.: What drew me to science was the thrill of exploring the unknown. Research creates new knowledge and pushes the limits of human understanding – a challenging but deeply fulfilling pursuit. Although my journey has been marked by failures and moments of doubt, even the smallest successes bring joy that keeps me going. One unforgettable moment occurred during the SAXO project, when we treated mutants with sucrose and observed cilia shedding. The whole lab was thrilled – we even joked that it was ‘so sweet it made the cilia fall off’. Though it turned out to be a false positive, that moment perfectly captured the joy and unpredictability that make science so captivating.

X.L.: Since childhood, I have been deeply curious about scientific research and always thought that becoming a scientist was a fascinating pursuit. I have had a particular interest in biology, especially in understanding how life is formed and evolves. Let me share an interesting story: when I was filling out my university application, I chose only biology-related majors, such as Biological Science and Biotechnology. I even applied for a wine brewing program, believing it was related to biological fermentation. Once I entered the field of research, I realized that it was full of challenges and difficulties, with experimental results often diverging significantly from my expectations. However, this only intensified my curiosity, because to me, ‘impossible’ means ‘I am possible’. I firmly believe that with persistent effort, success will eventually follow, and I thoroughly enjoy the satisfaction that comes from overcoming tough challenges.