A*STAR scientists from the Institute of Molecular and Cell Biology (IMCB) have identified what eluded yeast scientists for the past 100 years, by constructing stable haploid strains of Candida albicans, the most prevalent human fungal pathogen. This discovery, jointly made by two teams of scientists led by Prof Wang Yue of IMCB and Prof Judith Berman of the University of Minnesota, will enable scientists to effectively target and treat infections by Candida albicans. The findings, "The 'obligate diploid' Candida albicans forms mating-competent haploids", were published in the online issue of Nature on 30 January 2013.
Candida albicans ranks among the top four microbial pathogens in hospital-acquired infections of the blood, which has a mortality rate of as high as 45%. Currently, the choice of drugs for treating infections by this pathogen is limited, and drug-resistance has emerged worldwide, posing a great challenge to medicine.
Importance of the discovery
Nearly all other fungi have a haploid and a diploid phase in their life cycle, enabling the haploid cells to mate and generate genetic variations. However, up till this recent discovery, yeast scientists the world over had been unable to identify a haploid phase of this fungus.
Commenting on the significance of the discovery, Dr Mohan Balasubramanian, Senior Investigator at Temasek Lifesciences Laboratory and a leading yeast geneticist in the world, said, "The scientists show that the human pathogenic yeast Candida albicans, long thought of as always having two copies of each chromosome and no sexual reproduction in its life, in fact can and does exist as a sexually reproducing cell carrying only one copy of its genome."
Without a haploid phase, it is indeed extremely difficult for scientists to carry out genetic screens in fungi as this would require the precise targeting of both copies of a gene in a diploid organism to be able to observe a change, thus hindering the progress of the study of the virulence and delaying the development of effective treatment of fungal infections. With this discovery of the haploid phase in Candida albicans, however, scientists will now be able to easily target just one copy of the gene to observe a change, allowing for more successful screening and speeding up the discovery of targets for the development of drugs.
Prof Wang, who is a Research Director at IMCB, said, "Our discovery helps to fill a long missing gap in the life cycle of this important pathogen, greatly advancing our understanding of how it generates genetic variations for evolution and adaptation. At the same time, haploid Candida albicans also allows scientists to carry out traditional genetic screens that will certainly accelerate the identification of genes important for infection and drug targets for medical intervention."
Dr Balasubramanian said, "The paper by Wang, Berman and colleagues cuts across multiple fields, including evolutionary biology, genetics, and medical microbiology. The tools the authors have developed will help speed up the analyses of gene function in this important pathogen and might also therefore speed up our efforts to cure Candida infections".
Notes for Editor:
The research findings described in this media release can be found in the 30 January online issue of Nature, under the title, "The 'obligate diploid' Candida albicans forms mating-competent haploids", by Meleah A. Hickman1, Guisheng Zeng2, Anja Forche3, Matthew P. Hirakawa4, Darren Abbey1, Benjamin D. Harrison1, Yan-Ming Wang2, Ching-hua Su5, Richard J. Bennett4, Yue Wang2 & Judith Berman1,6
1 Department of Genetics, Cell Biology & Development, University of Minnesota, Minneapolis, Minnesota 55455, USA
2 Institute of Molecular and Cell Biology, Agency for Science, Technology & Research, Singapore 138673, Singapore
3 Bowdoin College, Brunswick, Maine 04011, USA
4 Department of Molecular Microbiology and Immunology, Brown University, Providence, Rhode Island 02912, USA
5 Department of Microbiology and Immunology, Taipei Medical University, Taipei, Taiwan
6 Department of Molecular Microbiology and Biotechnology, George Wise Faculty of Life Sciences Tel Aviv University, Ramat Aviv, 69978 Israel
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About Institute of Molecular and Cell Biology (IMCB)
The Institute of Molecular and Cell Biology (IMCB) is a member of Singapore's Agency for Science, Technology and Research (A*STAR) and is funded through A*STAR's Biomedical Research Council (BMRC). It is a world-class research institute that focuses its activities on six major fields: Cell Biology, Developmental
Biology, Genomics, Structural Biology, Infectious Diseases, Cancer Biology and Translational Research, with core strengths in cell cycling, cell signalling, cell death, cell motility and protein trafficking. Its achievements include leading an international consortium that successfully sequenced the entire pufferfish (fugu) genome. The IMCB was awarded the Nikkei Prize 2000 for Technological Innovation in recognition of its growth into a leading international research centre and its collaboration with industry and research institutes worldwide. Established in 1987, the Institute currently has 26 independent research groups, eight core facilities and 300 researchers.
For more information about IMCB, please visit 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 the lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based and innovation-driven Singapore. A*STAR oversees 14 biomedical sciences and physical sciences and engineering research institutes, and six consortia & centres, located in Biopolis and Fusionopolis as well as their immediate vicinity.
A*STAR supports Singapore's key economic clusters by providing intellectual, human and industrial capital to its partners in industry. It also supports extramural research in the universities, and with other local and international partners.
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Journal
Nature