Embargoed until 18.00 GMT 21 December 2005
GENOME DISCOVERY WILL HELP COMBAT DISEASE AND LEAD TO NEW DRUGS |
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An international consortium of researchers led by the University of Manchester has cracked the gene code behind a key family of fungi, which includes both the leading cause of death in leukaemia and bone marrow transplant patients and an essential ingredient of soy sauce.
The ‘genome sequences’ or genetic maps for the fungi Aspergillus fumigatus, Aspergillus nidulans and Aspergillus oryzae are published on 22 December in Nature magazine. Despite being from the same fungal family, they have been found to be as genetically different as fish and man.
Aspergillus is a very common air-borne fungus, carried all over the world as spores. Although usually harmless, the species Aspergillus fumigatus was identified as a cause of infection as long ago as 1848 and is now the leading infectious cause of death in vulnerable leukaemia and bone marrow transplant patients. Aspergillus nidulans has been a leading experimental system helping to unravel many fundamental cellular processes for the last 50 years, whilst Aspergillus oryzae has been used in the Far East for 2000 years to produce sake (rice wine), miso (soybean paste) and shoyu (soy sauce).
The researchers have found that the three species only display around 68% of the same proteins, a similar percentage to that shared by mammals and fish which diverged 450 million years ago. They also differ considerably in genome size, with Aspergillus oryzae being 31% bigger than Aspergillus fumigatus and 24% bigger than Aspergillus nidulans. Intriguingly, over 30% of the 9,500-14,000 genes identified are new to science and of unknown function and structure.
These results are being reported in three different papers in Nature, and reflect the efforts of an international collaboration of scientists and sequencing centres. The University’s Professor David Denning, who coordinated the project, said: “Fungi (including Aspergillus) play a critical role in the earth’s ecosystem, being responsible for almost all degradation of plant material as well as recycling nitrogen. Aspergillus fumigatus is a major constituent of compost, and mould fungi have been important sources of drugs including penicillin and ciclosporin (for transplantation).
“However, they are something of a Jekyll and Hyde and also produce toxins known as mycotoxins, such as aflatoxin which can cause liver cancer. Aspergillus causes a life-threatening infection for transplant and leukaemic patients, as well as being a major allergen for asthmatics.
“Identifying these genome sequences will transform scientific understanding of why this group of fungi is so lethal and allergenic. The importance of the project in helping develop new drugs and diagnostic tests, and understand and prevent allergies and diseases like pneumonia and sinusitis, cannot be overestimated. The information revealed will also develop our understanding of the biology of composting and mycotoxin production, and provide benefits for many other areas of science and medicine.”
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Notes for Editors
Movies and images to accompany this release are available at www.aspergillus.man.ac.uk/pressimages.htm. Professor David Denning will be available for filming/photography on 21 and 22 December or 23 December pm, as well as for interview by telephone.
Collaborators and Funding
A fungal genome workshop in the US in 1999, organised by the Burroughs Wellcome Fund, first supported the idea of identifying the genome sequence of Aspergillus fumigatus, and discussions within the National Institute of Allergy and Infectious Disease led to the funding of this project in September 2000. Half of the genome sequencing was undertaken at The Institute for Genome Research (TIGR) in Rockville, USA, where the genome for Aspergillus fumigatus was produced, whilst the other half was carried out at the Sanger Institute in Hinxton, UK, in association with the University of Manchester. This was funded by the Wellcome Trust, following initial funding from the Fungal Research Trust.
The sequencing of Aspergillus oryzae gene products originated in 1996 at the National Institute of Advanced Industrial Science & Technolology (AIST) in Tsukuba, Japan, and was extended from 1998 - 2001 by the collaboration of three national institutes, four universities, seven companies and two associations associated with Aspergillus oryzae in Japan. Genome sequencing of Aspergillus oryzae was undertaken by the public sequencing centre the National Institute of Technology and Evaluation (NITE), operated by Ministry of Economy, Trade and Industry (METI) which covered the cost supported by the companies in the consortium.
Aspergillus nidulans was sequenced by the Broad Institute of the Massachusetts Institute of Technology and Harvard University in Cambridge Massachusetts, which led the comparative analysis of the three species.
The Fungi
Aspergillus fumigatus is the most common Aspergillus species to cause disease, and is almost unique in causing infection at both extremes of the body’s immune function. Aspergillosis (the diseases caused by Aspergillus) mainly invade the lungs and sinuses, but can spread to other organs such as the brain. As well as leukaemia and bone marrow transplant patients, ‘invasive aspergillosis’ is increasingly affecting other hospital patient groups and is very difficult to treat. Up to half of sufferers die of the condition, and as many as 1 in 25 patients who die in modern European teaching hospitals are now suffering from it.
Other immuno-compromised patients (transplantation, AIDS, steroid treatment etc) are increasingly being affected with life-threatening Aspergillus pneumonia and sinusitis. Aspergillus can worsen asthma and cause allergic sinusitis in patients with allergic tendencies, and can also get into lung cavities created by tuberculosis (which affects a third of the world’s population) causing general ill-health and bleeding in the lung. The fungus also causes plant and animal diseases.
Common sources of Aspergillus include cellars, household plant pots, composting facilities, computers (including those in hospitals) and ground pepper and spices. Hospital construction projects have also been implicated in outbreaks.
Aspergillus nidulans, a classical genetic model for understanding basic genetics and fundamental cellular processes used since the 1940s, is central to efforts to understand and manipulate all the Aspergilli. It has provided a backbone of knowledge about the Aspergilli family and garnered the tools, knowledge and expertise to help understand their biology, including how their cells grow and undergo complex division patterns to generate new structures. In turn, this work has aided the development of other species into commercial powerhouses for the production of foodstuffs, industrially helpful enzymes and pharmaceuticals.
Now that the fungus’ genome has been determined researchers will be able to greatly expand and accelerate future research efforts, and new and exciting discoveries on basic cellular functions in general and the Aspergilli in particular are expected.
Aspergillus oryzae is widely used in traditional Japanese food fermentation which originated approximately 2,000 years ago in China, as well as for enzyme production by biotechnology companies, and the sales volume of industries with some relation to the fungus is believed to have reached 1% of the total Japanese GDP (approximately $50 billion per year). Its importance has led to it being known in Japan as ’kokkin’, which means ‘the national micro-organism’.
Aspergillus oryzae breaks starches down into sugars and proteins into peptide and amino acids by producing vast amounts of ‘hydrolytic enzymes,’ and recent developments have facilitated its use for the production of diverse proteins for industrial applications.
The University of Manchester (www.manchester.ac.uk) is the largest higher education institution in the country, with 24 academic schools and over 36 000 students in 2005/6. Its Faculty of Medical & Human Sciences (www.mhs.manchester.ac.uk) is one of the largest faculties of clinical and health sciences in Europe, with a research income of around £51 million, and the School of Medicine (www.medicine.manchester.ac.uk) is the largest of the its five Schools. It encompasses five teaching hospitals, and is closely linked to general hospitals and community practices across the North West of England.
For more information please contact:
· The Media Relations Office at The University of Manchester: o Jo Nightingale on 0161 275 8156/07717 881572/ jo.nightingale@manchester.ac.uk o Jon Keighren on 0161 275 8384 o Mikaela Sitford on 0161 275 2111/mikaela.sitford@manchester.ac.uk · Professor David Denning on 0161 291 5811/07802 482193 · Professor Geoffrey Turner of the University of Sheffield, an analyst of the sequencing information relating to mycotoxins, on 0114 222 6211/2000. · Dr Arnab Pain or Matt Berriman of the Wellcome Trust Sanger Institute on 01223 834244 |
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