Miao Gui

Ciliopathies are a heterogeneous group of genetic diseases involving infertility, recurrent respiratory infections, situs inversus, and other systemic abnormalities caused by ciliary dysfunction. The molecular diagnosis and treatment of these conditions have always been challenging. Traditional methods have identified some pathogenic genes while more remain to be uncovered, and the mechanisms by which gene mutations cause defects in ciliary assembly and motility remain unclear. The key obstacle behind these difficulties is the unknown molecular composition and assembly mechanisms of these large organelles​.

To tackle this problem, Miao Gui took a structural biology approach, shifting the traditional research focus to proteins, deeply analyzing the complex molecular composition and assembly mechanisms of cilia. He established a rapid and accurate protein identification and atomic model building method based on cryo-EM structure and AI-based structural prediction. This led to the near-complete atomic model of the ciliary axoneme containing 4 million atoms and over 200 ciliary proteins, greatly expanding the candidate gene library for ciliopathies​.These studies answered fundamental cell biological questions about the assembly and motility of cilia at the atomic level, while also proposing new diagnostic approaches for primary ciliary dyskinesia and other cilia-related genetic diseases. After establishing an independent lab, he continued to focus on the structural differences of cilia across different cells and species, identifying various sperm-specific microtubule inner proteins, and defining a new subtype of asthenozoospermia through clinical analysis​.

This work established a new paradigm for the study of ciliopathies (structure-based identification of pathogenic genes) and also holds promise for future research into other diseases​.