"in silico" subtractive screen

To identify the repertoire of specialized proteins needed for the formation and function of cilia, we developed a novel "in silico" subtractive screen¹. This screen led to the identification of a large, diverse group of ciliary genes, many of which, we have shown to be expressed only in ciliated cells and to be required for cilium formation. Using Drosophila as a model system we are studying the role of these genes, employing a multifaceted approach including: genetics, physiology, behavior, bioinformatics, biochemistry, fluorescent and electron microscopy.

We are particularly interested in the role of a family of six ciliary proteins collectively referred to as OSEGs, which are structurally related to transport proteins ¹. They are found only in organisms with cilia, and are expressed exclusively in ciliated cells. We have shown that OSEGs play a critical role in transporting the sensory machinery from the base of the cilium into its distal part. In addition we identified two other proteins through the in silico bioinformatics screen, that are related to small GTPase proteins that regulate other cellular transport events. Our results are starting to delineate a common foundation for the organization of intracellular transport systems, which: mediate internalization of surface proteins, transferring cargo between organelles, or delivery of components from the cell body to distal ciliary compartments.

¹ Avidor-Reiss T, Maer AM, Koundakjian E, Polyanovsky A, Keil T, Subramaniam S, Zuker CS (2004). Decoding cilia function: defining specialized genes required for compartmentalized cilia biogenesis. Cell , 117, 527-39. For abstract and PubMed link click here