ABSTRACT
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. Mohona Gupta is first author on ‘ Inpp5e is crucial for photoreceptor outer segment maintenance’, published in JCS. Mohona conducted the research described in this article while a Graduate student in Gregory J. Pazour's lab at University of Massachusetts Chan Medical School, Worcester, USA. She is now a Postdoctoral scholar in the lab of Markus Delling at University of California, San Francisco, USA, investigating how defects in primary cilia – cellular antennae essential for human health – trigger devastating multi-organ diseases, with the goal of developing new therapeutic strategies for currently incurable disorders affecting the kidneys and eyes.
Mohona Gupta
How would you explain the main findings of your paper in lay terms?
Our cells have tiny antenna-like structures called primary cilia that serve as communication hubs, helping cells receive and process important signals. When these cellular antennae don't work properly, it can lead to serious diseases affecting multiple organs, like the kidneys, brain and eyes. In our study, we focus on a protein called Inpp5e, which is essential for the proper functioning of these antenna-like structures, particularly in the light-sensing cells of the eye (photoreceptors). When we remove Inpp5e from these cells, we discover that the structures become disorganized and shorter than normal. As a result, crucial proteins are unable to reach their proper destinations and get stuck in the wrong parts of the cell. Additionally, the cellular scaffolding that maintains the shape of these antennae deteriorates. When they stop working properly, the light-sensing cells can't function and die, ultimately leading to vision loss. This discovery deepens our understanding of why mutations in the INPP5E gene cause vision problems and points us toward potential new ways to treat these conditions.
When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?
The path to discovery is rarely straightforward. We thoroughly characterized our Inpp5e-knockout mice and found clear issues with their photoreceptors, but the underlying molecular mechanism remained elusive. The breakthrough came when we discovered that actin, which is essential for forming new light-sensing discs, was missing from the base of the outer segment. This finding directed our attention to disc formation, which we confirmed to be defective using electron microscopy. This revelation provided crucial insight into how the loss of Inpp5e leads to vision problems.
Why did you choose Journal of Cell Science for your paper?
We chose Journal of Cell Science because it is highly respected in the field of cell biology, offers rapid review times and provides good visibility. The journal is particularly well-regarded for studies on cellular mechanisms and structures, making it a perfect fit for our work exploring how Inpp5e regulates photoreceptor cell biology and protein trafficking. In addition, Journal of Cell Science has published many significant papers in ciliary biology and photoreceptor research, ensuring our findings will reach the appropriate audience of cell biologists and vision researchers.
Watching cells talk – how disrupted communication in primary cilia triggers kidney disease and blindness.
Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?
An exceptional mentor like Gregory J. Pazour, my thesis advisor, taught me that science is not just about finding answers, but about asking relentless questions. He showed me that true discovery emerges through rigorous testing, challenging assumptions and exploring multiple methodological approaches to test a hypothesis. The goal is not just to gather data, but to build knowledge that stands the test of time – resilient, trustworthy and transformative.
What's next for you?
I am committed to pursuing a career in academic research, with the goal of establishing an independent research program that builds on my expertise in ciliary biology and cellular mechanisms. I want to explore fundamental questions about how cells maintain their specialized structures and how disruptions in these processes leads to disease. Academia offers the intellectual freedom to pursue these complex scientific questions while providing the opportunity to mentor the next generation of scientists. My experiences as a graduate student and postdoctoral researcher have reinforced my passion for discovery-driven research and strengthened my resolve to contribute to our understanding of cellular biology through an academic career.
Tell us something interesting about yourself that wouldn't be on your CV
Beyond my scientific work, I am passionate about Indian classical dance. The precision and grace required in dance surprisingly parallel the meticulous nature of scientific research, though in a completely different realm. This artistic pursuit not only helps me to maintain balance in my life but also keeps me connected to a rich cultural tradition.
Scientific research can be challenging, with experiments often not working as expected. What keeps you motivated during difficult periods, and what advice would you give to early-career researchers facing similar challenges?
In research, setbacks and failed experiments are part of the journey toward discovery. What keeps me motivated is recognising that each ‘failed’ experiment teaches us something – even if it's just learning how not to do something. I also find it helpful to step back and look at the bigger picture of what we're trying to accomplish. My work on cellular mechanisms has the potential to help patients with vision disorders, and that larger purpose helps me put daily frustrations into perspective. For early-career researchers, I encourage developing a support network of colleagues who understand your challenges. Celebrate small victories and make time for interests outside the lab – Indian classical dance, for me, serves as a refreshing counterbalance to research. Finally, remember that every established scientist has faced similar challenges. Persistence, combined with creativity in problem-solving is essential for moving forward.
Mohona Gupta's contact details: University of California, San Francisco, Arthur and Toni Rembe Rock Hall, 1550 4th St, San Francisco, CA 94158, USA.
E-mail: [email protected]