Sensing and responding to the environment is critical for all living beings. Most sensory system utilizes cilia to sense stimuli and convert into physiological response. Cilia are microtubule-based motile and sensory organelles that extending from the cell surfaces of virtually all eukaryotic organisms. Although identified nearly 100 years ago, the cilia were overlooked for a long time. Recently, researches from C. elegans and other model organisms implied a surprising connection between the defects in normal cilium sensory function and a wide spectrum of mammalian pathologies. Strikingly, in nematode C. elegans, many genes encoding ciliary components involved in cilia biogenesis and cilia function have mammalian counterparts that when mutated cause cilia diseases with renal cyst pathologies, such as Autosomal Dominant Polycystic Kidney Disease (ADPKD), Autosomal Recessive PKD (ARPKD), Nephronophthisis (NPHP), Bardet-Biedl syndrome (BBS) and Meckel-Gruber Syndrome (MKS). The evolutionarily conserved cilia pathological genes, ciliary localization, and sensory function make the nematode an attractive model to study cilia biogenesis, cilia function, and cilia-related human renal diseases.
The long-term goal of our lab is to understand how cilia form and function, and to relate these findings to human cilia diseases. Given that it is prohibitively difficult in humans to study the connection between ciliary formation, cilia function and disease, alternative experimental systems are necessary. In C. elegans we can explore all these questions in living animal. Such understanding is essential in order to identify the functions of the polycystins and many other cilia diseases genes, their role in disease processes, and their potential as therapeutic targets. Results of our proposed studies will provide new insight into the molecular basis of PKD disease and broaden our understanding of how cilia develop and function in normal and pathological states.