Hyperactive Protein Responses and Functional Residuomics of Cilia

I address how a cell governs hyperactive ciliary proteins. We found that RNA editing restricts hyperactive ciliary kinases by editing the kinase’s own message RNAs, reducing kinase translation (Li et al., Science, 2021). We find that sensory neurons dispose of a hyperactive intraflagellar transport (IFT) kinesin into the surrounding glia for clearance. We show that the kinesin conformation and activity are responsible for its fate. These results indicate that a living cell responds to hyperactive proteins through multiple unexpected pathways and that changing distinct residues trigger different cellular responses. We are using chemical mutagenesis and bioinformatics to systematically define functional residues essential for cilium assembly and performance.

Guangshuo Ou is a Professor and the Associate Dean at the School of Life Sciences, Tsinghua University, Beijing, China. The Ou laboratory studies the molecular and cellular regulations of neural development and has recently focused on how sensory neurons build up olfactory cilia. Guangshuo received his Ph.D. in Cell and Developmental Biology under the guidance of Dr. Jon Scholey at the University of California, Davis (2006). Afterward, Guangshuo was a Damon Runyon Postdoctoral Fellow with Dr. Ron Vale at the University of California, San Francisco (UCSF, 2007~2011). Guangshuo’s graduate and postdoctoral work were published in journals such as Nature and Science. Guangshuo started his first independent position as an awardee of the Junior 1000 Talents Program at the Institute of Biophysics, Chinese Academy of Science, in February 2011. The Ou lab was relocated to Tsinghua University in August 2013. The research findings from my group have been published in Science, Nature Biotechnology, EMBO Journal, Developmental Cell, Journal of Cell Biology, Current Biology, PNAS, and other journals. The Chinese National Science Foundation awarded Guangshuo the National Outstanding Young Scholarship in 2016. Guangshuo received the Newton Advanced Fellowship from the Royal Society and started his collaboration with Prof. Jordan Raff since 2015.