‘Worming a way out of Joubert Syndrome’
Joubert Syndrome (JS) is a rare inherited disorder associated with serious debilitating symptoms, including blindness, kidney cysts, developmental delays and mental retardation. The quality of life for patients and their families is therefore extremely challenging. The prevalence rate for JS is estimated at approximately 1 in 100,000; consequently JS has been designated an ‘orphan’ disease by the European Commission’s Rare Diseases Task Force. Comparatively little research has been carried out to date on JS and effective treatments remain elusive. The underlying cause of JS is thought to be at least in part due to defects in cilia, small hair-like projections that enable the cell to sense its environment and respond appropriately to signals in its locality, including the brain. For example, cilia can detect growth signals external to the cell and communicate this message to the internal control centre of the cell (nucleus), which then coordinates the correct growth response.
The worm species Caenorhabditis elegans is a small multicellular organism that is easy to breed, thus proving a useful experimental tool for studying genetics, cell biology and development. Using this model, research from Dr. Oliver Blacque and colleagues has recently shed light on the function of a protein called Arl13b, which is found in a mutated form in patients with JS. This research, carried out at the Conway Institute in UCD, involved tagging the equivalent protein in the worm (ARL-13) with a brightly coloured tag called a fluorescent marker, making it possible to localize it to a specialized region of cilia. The Blacque group further revealed that worms with a mutated form of this protein have abnormal cilia structure and behaviour, a reduced ability to sense the local environment, and a defective transport system within cilia (analogous to a railway network). Together, these abnormalities are proposed to compromise how cilia, and therefore cells, respond to signals during organism growth and development. Such protein malfunctions in the worm give us clues as to the causal reasons for the severe symptoms in patients with JS. Collectively these findings support a critical role for the ARL-13 protein for healthy cilia function, and compellingly implicate the human form as a potential therapeutic target for JS.
Commenting on their discovery, which was published recently in The Journal of Cell Biology, Dr. Blacque said ‘These findings provide a greater understanding of the mechanisms of Joubert Syndrome such that research in this area is directed towards increasingly promising therapeutic targets which will hopefully be of benefit to patients in the near future.’ This work, funded through Dr. Blacque’s SFI President of Ireland Young Researcher Award, is a primary example of how fundamental research in a worm has the capacity to inform investigation into the pathology of human disease and potentially open doors to new therapies.
