Bardet-Biedl syndrome (BBS), a rare condition that occurs in about 1 in 150,000 live births, is characterized by delays in mental development, early onset of blindness, short stature, extra digits on the hands and feet as well as kidney abnormalities and obesity. A new study by researchers at the University of California, San Francisco published online in the open-access journal PLoS Biology, has shed new light on the genetic disease Bardet-Biedl syndrome (BBS).

Even though the occurrence of BBS is rare, researchers hope to gain insight into molecular processes that control various functions, such as development, vision, kidney function and obesity by understanding the mechanisms of function of BBS genes and their protein products.

Once researchers discovered the mutations that cause BBS, they found a set of these genes encode for a protein complex required for the proper functioning of cilia. Cilia are found on the surfaces of many cells and consist of structures that resemble an antenna. Similar to antennae, cilia are significant for communication between cells given that many proteins containing cell-cell communication signals are located to these structures.

The UCSF researchers led by Dr. Kaveh Ashrafi report that their findings show that in addition to controlling incoming communication via the antenna-like cilia the mutations in BBS genes also control outgoing communication via the release of hormones. Dr. Kaveh Ashrafi, associate professor in the UCSF Department of Physiology who is also a member of the UCSF Cardiovascular Research Institute and the Diabetes Center, noted that counterparts of BBS genes are also found in the small roundworm Caenorhabditis elegans.

Irrespective of the obvious differences between humans and these microscopic worms, Ashrafi recognized that the way in which these evolutionary distant organisms work is similar to many basic mechanisms in cellular and animal physiology. Mutations in C. elegans genes remind of the symptoms in BBS patients, as they lead to abnormal feeding behavior and metabolism, smaller size and sensory defects. During their examination of bbs mutant C. elegans, the researchers unexpectedly discovered abnormally high levels of hormonal release in these mutant animals. They established that they could restore the worm’s normal feeding, body size and metabolism by blocking the bbs worms excess release without correcting defects in the cilia.

Dr. Ashrafi explained:

“Good communication is key to any relationship, and cells are no exception. This work expands understanding of molecular roles of BBS proteins and suggests that excessive hormonal release could underlie some of the symptoms seen in BBS patients, and thus opens up therapeutic avenues. Of course, we are a long way from knowing that for sure in human. While it is natural to consider all of the complexities of human physiology, it is precisely the simplicity of C. elegans and its amenability to experimentation that is helping us to learn the basic functions of some human disease genes.”

Funding: B.H.L. is supported by NIH Institutional NRSA #5T32HL007731. This work was supported by grants from the Kinship Foundation Searle Scholar’s Award, The Burroughs Welcome Career Award, The PBBR program at UCSF, and NIH R01 (DK070149) awards to K.A. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Written by Petra Rattue