First person – Rupalatha Maddala

Rupalatha Maddala

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

The transparent lens in the eye is crucial for focusing light onto the retina, allowing us to see clearly. This lens is composed of two main types of cells – epithelial cells and fiber cells. The fiber cells make up most of the lens and are packed with proteins that help with transporting water, ions and nutrients, maintaining cell structure and holding cells together. For the lens to work properly, fiber cells need to keep their unique hexagonal shape, stay connected and maintain well-organized proteins on their surfaces. Despite the importance of these proteins, very little is known about how they are organized within the lens. In this study, we create a specialized mouse model lacking a protein called ankyrin-B, which acts as a scaffold, or structural support, for other proteins in the lens. We find that without ankyrin-B, fiber cells lose their shape, become less organized and have weaker connections with each other. Key proteins like water channels, gap junctions and ion channels also become disorganized and unstable, affecting the flow of water and ions within the lens. This disruption leads to cataract formation, poor lens growth and decreased stiffness. Our findings highlight the essential role of ankyrin-B in keeping the lens clear and flexible, which is vital for healthy vision.

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

Our research project was initiated just before the COVID-19 pandemic, which presented significant challenges in maintaining the ankyrin-B conditional knockout mouse model developed specifically for this study. As a result, although we had planned additional mechanistic studies to explore the role of ankyrin-B in lens function more comprehensively, we had to prioritize only the most essential analyses to complete the project. Additionally, we encountered a learning curve with 3D imaging and rendering techniques, as these were new to our team. Fortunately, Dr Vann Bennett's laboratory, which discovered the ankyrins, provided invaluable support. Their proximity and support were instrumental, as Dr Bennett's lab generously shared tools, including antibodies, protocols and gene-targeted mice, which were crucial for the successful completion of this project.

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

Yes, we had a striking ‘eureka’ moment that profoundly shaped our study. During our experiments, we observed a unique lens phenotype (cataract development and reduced lens size in ankyrin-B conditional deficient mice) starting with sutural abnormalities precisely after postnatal day 14 (P14) and continuing from the P16 stage with notable disruption in fiber organisation. This pattern suggests the involvement of unique temporal and spatial mechanisms in maintaining lens cytoarchitecture, growth and clarity. This discovery was very much unanticipated and led us to investigate further, ultimately revealing crucial insights that reshaped our understanding of the molecular mechanisms regulating the development of fiber cell lateral membrane paddles, protrusions and ball-and-socket interdigitations. This moment of discovery underscored the significance of our research and reinforced our commitment to exploring the underlying biology in greater depth.

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

I always admired the quality of papers published on the cell biological aspects in the Journal of Cell Science and the expertise of its editorial board members.

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

My postdoctoral mentor, Dr Vasantha Rao, provided unwavering support, resources, and encouragement, enabling me to explore my research projects fully. During my postdoctoral training, and now as a junior investigator, I have been fortunate to learn from our collaborators both within and beyond our department, whose insights have also greatly enriched my development.

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?

After I finished my Master's degree in Life Sciences, I joined the National Institute of Nutrition, Hyderabad, India as a research scientist to participate in an international collaborative research project focused on the nutritional benefits of different plant-based oils. At this federal institute, there were several graduate students and I regularly attended various scientific seminars. This environment encouraged and motivated me to pursue a graduate degree in biomedical research. After obtaining my PhD, I moved to Duke University Medical Center for postdoctoral training in the Department of Ophthalmology. In Dr Vasantha Rao's laboratory, I worked on projects related to the lens and trabecular meshwork, focusing on cytoskeletal biology and its role in lens growth, development and function, as well as homeostasis of aqueous humor outflow and intraocular pressure. Our lab was focused on basic science, disease mechanisms and finding the molecular targets to treat cataract and glaucoma. I was very productive in these different projects, participated in other postdoctoral and student research projects and I was involved in training and mentoring several students. This background and experience have been highly satisfying and encouraged me to continue my career in biomedical research.

Who are your role models in science? Why?

Certainly, my postdoctoral mentor is one of my primary role models, continuously inspiring me to pursue my career in biomedical research. My younger sister, who is just two years younger than me, is a chemistry professor. She has trained several graduate students and has become a college principal. I greatly admire her accomplishments, and we are currently exploring collaborative projects related to cytoskeletal-targeting drugs for lowering eye pressure. Additionally, I deeply admire the pioneering work of leading scientists who have contributed to our understanding of the regulatory mechanisms of the cytoskeleton and cell adhesion.

What's next for you?

I am deeply committed to continuing my academic career, focusing on the biology of ocular tissues, their function and the treatment of ocular diseases. I have recently submitted an NIH grant application and am hopeful to secure independent funding to advance my research in this area.

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

I have a passion for gardening, where I enjoy growing a variety of flowers and vegetables. Cooking is also one of my hobbies, allowing me to make the most of what I grow. In addition to these personal interests, I actively participate in social activities, raising funds for non-profit organizations, including the Association for India's Development.