Worming Out Answers About Cilia and Disease

 

Posted: 05 October 2012

What can a tiny worm tell us about human disease? Plenty, if you know what questions to ask and how to wriggle out the answers. And Dr Oliver Blacque does. He is looking to a roundworm to find out more about tiny structures called primary cilia, because it’s now emerging that when something goes wrong with such cilia in humans, disease can follow. Primary cilia are tiny, non-moving appendages that stick out of various cells in the body, and they crop up all through the animal kingdom.

Until recently they were thought to be ‘vestigial’ structures. But recently the field of cilia biology has blown open, and primary cilia are now thought to play roles in sensory processes, including vision, taste, smell and development explains Dr Blacque, who studied biochemistry at UCD and is now a Principal Investigator and College Lecturer at the UCD School of Biomedical and Biomolecular Science.

“Probably the biggest interest in the field is how cilia sense chemical signals and co-ordinate processes in our bodies,” he says. Cilia dysfunction has been linked to several medical disorders in humans, many of which are rare, but cilia problems are also behind a more common genetic disorder called autosomal dominant polycystic kidney disease, which damages the kidneys over time.

While working as a post-doctoral researcher at Simon Fraser University in Canada, Dr Blacque made a major breakthrough that linked another condition called Bardet-Biedl syndrome (BBS) with primary cilia problems. The list of symptoms in BBS is long - blindness, infertility, mucus in the lungs, organs on the wrong side of the body, kidney defects, bone abnormalities, protruding features on face, fluid build-up in brain, obesity, muscle movement problems and diabetes rank among them - but this just shows how widespread the effects of cilia are, he says.

“We realised the genes behind BBS were also important for maintaining normal cilia function, and that led me into the cilia field.” Dr Blacque returned to UCD and through a Science Foundation Ireland President of Ireland Young Researcher Award he established a lab to look at cilia disease using worms. But these are not just any worms. He is using a tiny roundworm called Caenorhabditis elegans, which is a workhorse of scientific studies: the tiny worms are easy to grow and they share many of the same genes as humans.

“We know that most biological processes share great overlap between simpler and more complex systems,” he says. “We wanted to know about the basic properties of cilia-disease genes, and by looking in the worm we have experimental advantages to answer that question a lot faster.”

A key approach he takes is to knock out the genes in question in the worm. Then by looking at what happens when a particular gene is no longer functioning, he can get insight into what that gene normally does.

“If you were an alien from outer space and you didn’t know how a car worked, you might take out the engine first and see that it didn’t move, so you know the engine is involved in movement - we do the same thing genetically,” he explains.

Dr Blacque is particularly interested in how cilia-disease genes affect the movement of molecules in cilia. By labelling proteins in the worm and watching under the microscope in real time he can see what happens to trafficking in and out of the cilia when genes of interest are missing. His work - on which he collaborates with colleagues in Canada and Europe - has already identified important genes for controlling entry and exit of molecules into the cilium at its base, and the hope is that the findings will help to shed light on disease processes: “We feel that by teasing out the transport function of the cilia-associated genes we will get a better understanding of how disorders can arise when cilia are not functioning.”

Dr Oliver Blacque is funded primarily by Science Foundation Ireland. He was interviewed by freelance journalist Dr Claire O'Connell.