Researchers at the Department of Biology at Maynooth University have made a significant breakthrough in the study of the human pathogenic fungus, Aspergillus fumigatus. The fungus, which severely affects some cancer patients, produces a toxic molecule, gliotoxin.
The toxin causes disease in immune-compromised patients such as cancer sufferers and is also a major issue in food safety. The researchers had previously discovered that the toxin actually damages the fungus itself, but that the production of the toxin stimulates repeat production (a positive feedback loop).
Stopping the loop
The scientists have now discovered that a new molecule (GtmA) shuts down the mechanism causing the repeat production. This type of molecular ‘off-switch’ has never been seen before in biology, and may form the basis of a therapy to treat aspergillus infection in patients.
Discussing the breakthrough, Professor Sean Doyle, Department of Biology, Maynooth University, said he believed the breakthrough could form the basis of treatment for patients in the future.
“This is a major breakthrough because if we can discover exactly how toxin production is switched off in one fungal species, this will provide insights into how we can do it in other human, animal and plant disease-causing fungi.”
“This might form the basis of a therapy to treat aspergillus infection in patients, which can have a significant impact for cancer, organ transplant, cystic fibrosis and chronic obstructive pulmonary disease (COPD) patients,” he said.
Following on from the discovery, Professor Doyle hopes that medication and food additives can be developed to combat the toxin.
“We’ve made a number of discoveries in our study of this fungus over the past few years but this is one of the most significant. It may lead to pharmaceuticals and food additives which can diminish the production of this extremely damaging toxin,” he added.
The next step
The Maynooth University team now intends to further explore the wider impact of their findings and also investigate if, and how, similar systems operate in other fungi which make gliotoxin, and related toxic molecules. The work has significant biomedical and biotechnological applications and they hope to work with pharmaceutical companies interested in anti-fungal drug development.
The research has been funded by Science Foundation Ireland and the Irish Research Council, and the breakthrough has just been published in the prestigious Cell Press journal Chemistry & Biology. The team of seven researchers at Maynooth University, led by Professor Doyle, has been pioneering investigations for several years into gliotoxin, making a number of key breakthroughs into the little understood toxic molecule which was first discovered in 1936.
The project involves a major collaborative effort between Maynooth University biologists Professor Sean Doyle, Dr. Gary Jones and Dr. David Fitzpatrick, along with PhD student Stephen Dolan, Dr. Rebecca Owens and Dr. Grainne O’Keeffe.
Biology at Maynooth University
Biology is the study of life – everything from the tiniest microbe to entire ecosystems that spread across the planet. And understanding more about life will help us to tackle major societal challenges, including human and animal health, food security and the effects of climate change.
Since its inception in 1970, the Department of Biology at Maynooth University has expanded steadily in terms of numbers of undergraduates, postgraduates, post-doctoral staff and academic and support staff, and in the range of courses offered. Current programme offerings include the BSc Biological and Biomedical Sciences and the BSc Biotechnology, the MSc Immunology and Global Health, the MSc Biology (research) and the PhD Biology.
Recent funding success has funded not only projects and researcher salaries, but has enabled the purchase of the most advanced technologies for molecular, proteomics and bioinformatics research. Biology at Maynooth University is one of the best equipped and resourced biological research departments in Ireland.
Promoting research collaboration
The research activities of the Maynooth University Department of Biology have increased significantly in scope and the Department has established an international reputation in Biological Control, Bioinformatics, Immunology, Medical Mycology, Molecular Genetics and Plant Biotechnology.
Traditionally, researchers in individual fields within Biology may not have had much interaction with each other. But by sharing technologies, working together across these disciplines and asking new questions, researchers at Maynooth University are gaining new insights into how life works.
Recent outputs from the Department include publications in high-impact journals, such as Nature Immunology, Cell, PLOS Pathogens and PNAS, and the development of two campus spin-out companies: Profector, which provides technology for genetics and biomedical research and drug delivery, and Beemune, which seeks to protect the health of bees.