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Scrutinizing Organelles
March 29, 2012   
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The disrupted functioning of cilia, the inconspicuous organelles present on the surface of cells of nearly all organisms, is the source of many diseases in humans.

The Nencki Institute of Experimental Biology in Warsaw has launched research under a grant that aims to help scientists better understand the structure and functioning of cilia, in both protozoa and mammalian cells.

Apart from fungi and higher plants, almost all cells—from the protozoa to human cells—are equipped with short projections called cilia. Cilia receive stimuli from the environment, move the entire cell or transport fluids and particles in its immediate vicinity. Even though these organelles are common, surprisingly little is known about their structure and functioning. At the same time, their disordered functioning in humans underlies many diseases, so-called ciliopathies. Scientists from the Nencki Institute of Experimental Biology are hoping to uncover some of the secrets of the cilia using the prestigious EMBO Installation Grant.

“Cilia are very interesting organelles,” says Dorota Włoga, Ph.D., who is putting together a research team to study organelles at the Laboratory of Physiology of Cell Movements at the Nencki Institute. “They usually range in length from a few to a dozen or more micrometers; the latter are called flagella. Their skeleton is made of microtubules, which are tiny tubes built out of a protein called tubulin.”

Depending on certain differences in their ultrastructure, the cilia are either immobile or able to move. Individual immobile cilia (primary cilia) play important sensory functions: they receive stimuli from the environment and transfer them into the cell. For humans as well as other organisms, this is of fundamental importance. The lack of or defective functioning of these cilia may lead to cyst formation within the kidneys, polydactyly (additional fingers or toes) or obesity. Highly transformed cilia are found, for example, in the rods in the retina of the eye and damage to these is responsible for sight disorders.

Mobile cilia enable spermatozoons and certain types of unicellular organisms to move, but some may also have sensory functions. Synchronized beating of the cilia of epithelial cells moves mucus (e.g. within the airways) or is responsible for transporting particles (e.g. ovum in the fallopian tube).

“Recently Japanese researchers have shown that mice with disordered functioning of cilia within the epithelium lining the airways experience problems with getting rid of mucus and make sounds resembling sneezing and coughing,” says Włoga.

The existence of cilia has been known for a long time. But researchers still know little about the details of their structure and functioning.

“According to current estimates, even 500-600 proteins may be involved in the assembly and function of a single cilium,” says Włoga.

The researchers at the Nencki Institute of Experimental Biology aim to find new, potentially cilia-related proteins and investigate whether they are located in the cilia and how they impact the structure and functioning of the cilia. Research is being conducted on a protozoan called Tetrahymena thermophila, a model organism allowing scientists to conduct analyses at the ultrastructural, biochemical and molecular level.

In the second phase of their research, the scientists will investigate whether the proteins identified in protozoa as cilia-related have similar functions in mammalian cells.

“The evolutionary distance between protozoa and humans is immense,” says Włoga. “Therefore we will investigate if the function of the cilia-related proteins has been preserved during evolution. If yes, then the identified proteins will help us better understand the molecular basis of ciliopathy and in the future they may be used in medical therapy.”

The research on the cilia is being conducted under the five-year EMBO Installation Grant given to scientists by the European Molecular Biology Organization (EMBO), an independent foundation established to support the development of molecular biology in Europe. This grant allows scientists returning from abroad to establish and develop their own research groups and start collaborating with other scientists as part of EMBO.
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