Hairy discovery could yield genetic disease therapies
development of hair-like structures on cells - called cilia - that
when defective are involved in a range of diseases. They hope the
finding could lead to new drug targets in human infertility,
blindness, kidney disease and respiratory problems.
The team of biologists at the University of California, San Diego, in the US report in the 14 May issue of the journal Cell, identify six genes that are required for a cell to develop functional cilia.
UCSD's Charles Zuker and Tomer Avidor-Reiss said that the discovery of these genes provides medical researchers with a critical new tool to help in diagnosing genetic diseases where cilia do not work correctly and possibly in developing drugs that can minimise the health effects of such dysfunctions.
Avidor-Reiss said that recently scientists have begun to realise that there are links between cilia dysfunction and a wide range of human genetic diseases.
For example, in humans, sperm navigate toward the egg by propelling themselves with a type of cilia known as flagella. Defects in these whip-like cilia, result in non-motile sperm and male infertility, and are probably the most commonly known type of cilia dysfunctions.
Other widely known human cilia disorders include the pulmonary diseases caused by defective respiratory cilia, which cleanse the lungs by sweeping mucous and trapped particles into the throat, and the vision problems or blindness due to defective cilia in the eye's photoreceptors.
Several human genetic ailments affecting multiple organs have their origin in the absence and dysfunction of cilia, as well, according to the scientists. These include polycystic kidney disease, the most common genetic cause of kidney failure; embryonic problems in the body's right-left symmetry that cause organs to develop on the wrong side of the body; and Bardet-Biedel syndrome, a rare genetic disorder characterised by obesity, learning disabilities and eye and kidney problems.
Zuker's team conducted genome-wide analyses of a wide range of organisms - ranging from the single-celled parasite responsible for malaria to humans - in their search for the genetic machinery of cilia formation. From a total of around 150,000 genes, they identified 200 used by a number of species to make cilia.
The researchers then homed in on 40 genes important for a type of cilia found in human, mouse, fruit fly and roundworm cells, then demonstrated, in a series of experiments in fruit flies (Drosophila melanogaster), that six of those genes were integral for the formation of cilia. This was done by attaching a fluorescent protein to the proteins produced by the candidate genes that end up at the base of the fly's back bristles, a form of sensory cilia used by flies to sense their position in space and steer as they fly.The next stage in the research is to assign specific functions to the genes, to determine their specific role in cilia assembly.
