The role of actin dynamics in organizing cilium structure and function
Kae Whiting (ESR2)
Kae grew up in Utah in the United States, and obtained their Bachelor of Science in Biology from Saint Mary’s College of California. While there, they had the opportunity to spend a summer performing independent research on the role of microRNAs on dendritic growth in sympathetic neurons which cemented their interest in research and cell biology. Kae then continued their studies at the University of Edinburgh, where they earned their Masters of Science in Integrative Neuroscience. During their time in Scotland, Kae completed two research projects under the supervision of Dr. Thomas Theil: the first used cerebral organoids as a model system to study the role of sonic hedgehog signalling through the primary cilium during human cortical development; the second used bioinformatic analyses to determine roles of primary cilia in cortical development. These projects let them to pursue their PhD in the Department of Genetics at Radboud University Medical Center, where they will be studying the role of actin dynamics in organizing photoreceptor connecting cilium structure and function.
Prospective defence date: Summer/Autumn of 2025
Currently I am working hard to finalize my PhD. After that is complete I look forward to continuing researching as a postdoc in the cilia field.
What does Kae say about our program?
Being part of the SCilS consortium has given me a truly unique PhD experience that exceeded all expectations. The program fostered a highly collaborative environment, promoting information exchange and networking opportunities that not only supported my PhD research but will continue to benefit my career beyond graduation. Additionally, the opportunity to visit other labs and work at different institutions during secondments allowed me to expand my research skills and fostered my growth as an independent scientist. Most importantly, sharing the journey with the 13 other brilliant ESRs provided invaluable support through the typical ups and downs of a PhD program. We laughed, cried, and celebrated together, forming lasting friendships that will extend beyond the consortium. This experience has been incredibly enriching on both a professional and personal level, and I cannot thank the entire consortium enough for the opportunity SCilS provided.
Abstract
The relationship between actin and the cilium is a complex one. F-actin depolymerization can promote ciliogenesis and cilium elongation, but also results in cilia shortening or deciliation. We discovered that a WASF3-ARP2/3 axis drives ciliary membrane evaginations in photoreceptor sensory cilia, initiating the formation of the stacked, opsin-filled membrane discs that allow phototransduction, but the details of which are not known. Defects in this process leads to inherited retinal degeneration (IRD). This project will use optimized CRISPR/Cas9- based genome editing of isogenic hiPSC lines to tag endogenous retinal ciliopathy-associated proteins suspected to participate in this process (SPATA7/RPGRIP1, INPP5E/TULP3, BBS4/6), with epitopes optimized for STORM superresolution localization (mNeonGreen and mScarlet), live cell proteomics by proximity labelling (TurboID/MS, in collaboration with P7-EKUT), and live cell imaging (mNeonGreen- Lifeact). These procedures will be deployed at different timepoints of differentiation into photoreceptor precursors and organoids to establish the dynamics of the actin assembly process during the first stages of photoreceptor cilium development, and its loss in IRD by evaluating isogenic patient vs control lines.
We want you to understand!
Layman abstract
Using mini-eyes to shed light on inherited blindness
Photoreceptors are specialized cells in the retina of the eye that sense light, allowing us to see. To work properly, photoreceptors need to be constantly renewed with the help of a protein known as actin. Changes in genes that control actin can lead to inherited blindness.
In my project I am interested in studying the role of these genes in photoreceptor development and disease. To do this, we use adult stem cells to make miniature retinas, allowing us to study the development of human photoreceptors. We hope that by understanding how these proteins function in the photoreceptor we can develop treatments for people with inherited blindness.
