Zebrafish genes linked to human respiratory diseases

A*STAR scientists have discovered genes in this tropical freshwater fish which may be synonymous with the genes for developing hair-like structures in the human airway

2014-09-15

(Press-News.org) Singapore, 15 September 2014—A small freshwater fish found in many tropical aquariums may hold the key to unlocking one of the leading causes of respiratory diseases in humans.

Scientists from A*STAR's Institute of Molecular and Cell Biology (IMCB) have identified hundreds of novel genes in the zebrafish that could be functionally identical to the human genes required for forming motile cilia, hair-like structures on the surface of airway cells. These are required for removing dust and pathogens from the human airway. The study showed that the loss of these genes is linked to development of defective motile cilia, which could be the cause of some respiratory diseases.

Primary Ciliary Dyskinesia (PCD) is a rare genetic disorder which results in defective motile cilia within the human airway. Defective motile cilia cannot function properly to remove dust and bacteria from the lungs, leading to a range of respiratory problems, including chronic lung infections such as bronchitis and pneumonia, and in more severe cases, causes long term damage to the airway.

Reported recently as a cover article in Development, a leading research journal in developmental biology, the IMCB research team identified hundreds of novel genes that are associated with the development of motile cilia via genetic screening in zebrafish. Out of nearly 600 genes found in the zebrafish, the researchers identified almost all of the 26 known genes responsible for PCD, implying that many more could be linked to the disorder.

Further studies on this discovery can yield useful information to pinpoint the genes associated with PCD. These genes may be valuable markers for the accurate diagnosis of PCD and other causes for defective motile cilia via genetic testing. This will in turn allow healthcare practitioners to implement mitigation strategies early.

"There is no cure for PCD. Doctors can only prescribe aggressive treatments to slow the progress of airway damage and address the respiratory issues resulting from PCD. It is therefore important to identify the genes responsible in a precise manner and diagnose the condition early," said Dr Sudipto Roy, Senior Principal Investigator at IMCB and the lead scientist for the study. "Our collection of genes will be invaluable for understanding how cilia are made and what cause them to be defective. They are important clues for understanding cilia-related diseases, and to develop future treatments," he added.

Professor Hong Wanjin, Executive Director of IMCB, said, "Developmental biology seeks to understand the basic principles governing the development of humans and how the emergence of complexities can be implicated in human diseases. This is exemplified in our study, which has uncovered the links between human diseases and the genes involved in cilia formation. Such foundational research is crucial as practical applications of research outcomes need to be grounded in fundamental science."

INFORMATION: IMAGES

Image 1: Human airway cells produce hundreds of motile cilia. Cilia are labelled in green, cell membranes in red, and nuclei in blue.

Notes to Editor:

The research findings described in this media release can be found in the Development Journal, under the title, "Systematic discovery of novel ciliary genes through functional genomics in the zebrafish" by Semil P. Choksi1, Deepak Babu1,2, Doreen Lau1, Xianwen Yu1,* and Sudipto Roy1,2,3,4

1Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673; 2NUS Graduate School of Integrative Sciences and Engineering, Centre for Life Sciences, 28 Medical Drive, Singapore 117456; 3Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543; 4Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore,1E Kent Ridge Road, Singapore 119288; *Present address: Department of Biological Sciences, Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.

Full text of the Development paper can be accessed online from: http://dev.biologists.org/content/141/17/3410.full?sid=3e92ba95-1416-4e94-97a0-1180801d81da For media queries and clarifications, please contact:

Tan Yun Yun
Senior Officer, Corporate Communications
Agency for Science, Technology and Research
Tel: +65 6826 6273
Email: tan_yun_yun@a-star.edu.sg About the Institute of Molecular and Cell Biology (IMCB) The Institute of Molecular and Cell Biology (IMCB) was launched on 23 January 1985, with its official opening ceremony held on 2 October 1987 at the National University of Singapore (NUS). It subsequently became an autonomous research institute (RI) of A*STAR, moving to Biopolis in 2004. IMCB's vision is to be a premier cell and molecular biology institute which addresses the mechanistic basis of human diseases and its mission is to conduct cutting-edge discovery research in disease pathways; to groom early career researchers to be future leaders in research; and to collaborate with medical and industry communities for research impact. IMCB plays an important role training and recruiting scientific talents, and has contributed to the development of other research entities in Singapore. Its success in fostering a biomedical research culture in Singapore has catalysed Singapore's transformation into an international hub for biomedical research, development and innovation. Funded primarily by the Biomedical Research Council (BMRC) of A*STAR, IMCB's current discovery research includes cell biology in health and disease; animal models of development & disease; cancer & stem cell genetics & genomics; and structural biology & drug discovery. IMCB's translational research includes humanised model organisms for human diseases; systems approach for disease target identification & validation; and protein engineering & antibody development for diagnostics & therapeutics. Research activities in IMCB are supported by cutting edge infrastructure and facilities including quantitative proteomics; humanised mice; mouse models of human cancer; protein crystallography X-ray; zebrafish for drug metabolism & toxicology; advanced molecular histopathology; imaging & electron microscopy; and DNA sequencing. For more information about IMCB, visit http://www.imcb.a-star.edu.sg. About the Agency for Science, Technology and Research (A*STAR) The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector agency that fosters world-class scientific research and talent to drive economic growth and transform Singapore into a vibrant knowledge-based and innovation driven economy.

In line with its mission-oriented mandate, A*STAR spearheads research and development in fields that are essential to growing Singapore's manufacturing sector and catalysing new growth industries. A*STAR supports these economic clusters by providing intellectual, human and industrial capital to its partners in industry.

A*STAR oversees 18 biomedical sciences and physical sciences and engineering research entities, located in Biopolis and Fusionopolis, as well as their vicinity. These two R&D hubs house a bustling and diverse community of local and international research scientists and engineers from A*STAR's research entities as well as a growing number of corporate laboratories.

For more information on A*STAR, please visit http://www.a-star.edu.sg

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Zebrafish genes linked to human respiratory diseases

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