Fighting Fungi

Fungi live inside each and every one of us: they can appear on our skin, our mucous  membranes, our nails and even in our guts. Fungi are harmless – in fact, they even form part of our body’s natural flora. But if our immune system is severely compromised, fungi can cause serious diseases. And it’s precisely these life-threatening, invasive fungal infections that the Transregional Collaborative Research Center, FungiNet, is looking into.

Dr. Axel Brakhage in front of one of the ZEISS microscopes in his lab. Image Courtesy: HKI

“Every year, two million people across the world contract an invasive fungal infection, which causes as many deaths as malaria or tuberculosis annually,” says Dr. Axel Brakhage, Director of the Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute (HKI) and Chair of Microbiology and Molecular Biology at Jena University.

He estimates that the disease has affected four times as many people over the past 20 years. Cancer patients, those suffering from HIV and AIDS, and people who have received transplants are particularly at risk – in more than 50% of cases, a fungal infection will end in death. It’s still very diffcult to diagnose, and diseases are often detected either too late or not at all.

“Fungi manifest in ways we still know very little about,” says Brakhage.

That’s why, in October 2013, more than 60 scientists from the HKI, the Friedrich Schiller University of Jena and the University Hospital in Jena joined forces with staff at the University of Würzburg and its hospital to develop new diagnostic and treatment strategies as an interdisciplinary team. Brakhage and his team have specialized in the mold fungus Aspergillus fumigatus and the yeast fungus Candida albicans.

A colony of the yeast fungus Candida albicans. Image Courtesy: HKI

“We want to find out why these fungi are so aggressive and how they overpower the immune system,” explains the microbiologist. To this end, they are examining clinical samples and using ZEISS microscope systems to observe how the body’s own immune cells and the pathogens interact with one another. The biologists are using microscopy techniques capable of imaging living cells. This is known as live cell imaging.

“By observing the cells, we can see what they’ve experienced,” says Brakhage.

Cells with a fighting spirit

As the different immune cells act like the body’s police, doing battle with pathogens and storing this information for future attacks, they are particularly interesting for scientists: one team of researchers has been able to determine which immune cells in patients’ blood react to a fungal infection. For the group, this phenomenon even gave rise to a preclinical study. What’s more, the discovery of the first fungicide for Candida albicans caused quite a stir last year: the scientists were able to identify the poison that makes the yeast fungus so dangerous. This is another major move that will help us better understand how the disease manifests.

The mold fungus Aspergillus fumigatus as seen under the microscope. Image Courtesy: HKI

The studies in the lab and those performed using the microscope have generated enormous amounts of data. The bioinformaticians and system biologists at FungiNet can use them to quantify cellular processes on a computer and simulate bio-chemical processes, or even diseases themselves. “We want to create a virtual infection model that we hope will provide us
with many new theories and, ultimately, new findings, too,” says Brakhage, who was included in the internationally renowned American Academy of Microbiology this year for his outstanding scientific achievements. For the second funding phase, in May 2017, the German Research Foundation made 9.5 million euros available to FungiNet until 2021. For Brakhage, this is a symbol of the excellent work that the researchers have done in the fight to eliminate
fungal infections.

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