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Fighting pathogens with mini-pores and AI

Dr. Lara Urban is a scientist at the Pioneer Campus of Helmholtz Munich. Photo: Helmholtz Munich

At the Helmholtz Center in Munich Lara Urban is developing a rapid genetic laboratory for your pocket. Combined with artificial intelligence, she wants to use it to detect pathogens in the environment before they become a threat to endangered animals, and to us. 

Covid-19 was a wake-up call for the world. A global pandemic that would kill at least 20 million people caused by a virus from the animal kingdom (SARS-CoV-2) that was most likely fueled by the destruction of natural forest habitats in Southeast Asia. It has become clear since Corona the topic of health must in future be understood in a broader and more global context. “This is exactly what the One Health approach describes,” explains bioinformatician Lara Urban. “This concept, also known as ‘planetary health’, states that the health of all living beings - humans, plants, animals, microorganisms - and ecosystems on our planet are closely interrelated and must therefore always be considered together.”

One of the consequences of One Health is that zoonoses – infectious diseases that are transmitted between animals and humans – are much less common when ecosystems are intact and diverse. On the other hand, when natural habitats such as forests are encroached upon or destroyed by human activities, the result is monotonous habitats with low biodiversity. “Pathogens such as SARS-CoV-2 can evolve much faster and spread more easily in these uniform populations with low genetic diversity,” says Lara Urban. “By destroying the environment, we are not only contributing to the extinction of species, but also harming our own health. That’s why its so important to understand One Health better and to use modern technologies to do so.”

Lara Urban uses genomic technologies such as nanopore sequencing and combines them with artificial intelligence. Since 2022, she has led the Helmholtz Young Investigator Group “One Health”, which is based at Helmholtz AI and the Helmholtz Pioneer Campus in Munich. In 2023, she was honored for her research at the German Science Gala as Young Scientist of the Year 2022. In early 2024, the Federal Ministry for Economic Cooperation and Development (BMZ) appointed her to the German One Health Advisory Board.

“One goal of our work is the mobile and rapid detection of pathogens in nature,” Lara Urban explains. “To do this, we need to identify their genetic material in environmental samples.” This is currently only possible with nanopore sequencing in real time. A sequencing device the size of a USB stick contains a polymer membrane with tiny protein pores embedded in it. A voltage applied across the membrane creates a constant flow of ions through the nanopore. Special enzymes (helicases) then separate the double helix of the sample DNA. Finally, the single strand slides through the pore, disrupting the ion flow in a characteristic and measurable way, depending on the sequence of bases. “The result is a relatively noisy signal from which we can then use AI models and powerful processors to derive the real DNA sequence in real time and compare it immediately with reference data,” says the scientist. “This is a huge advantage over traditional sequencing, where you have to send samples to remote labs and wait several days for the results. We generate the data right on site in two hours.”

The portable mini-laboratory consists of a sequencing machine (top) and a computer (bottom) that can process and analyze data on the spot. Photo: Lara Urban

After studying bioinformatics and ecology at the Julius-Maximilian University of Würzburg and completing her PhD at the University of Cambridge, Lara Urban was awarded a Humboldt Fellowship to conduct postdoctoral research in New Zealand. There, she worked intensively on monitoring endangered species, such as the flightless Kakapo parrot, of which only 248 individuals remain on some of New Zealand's offshore islands. “As a result of inbreeding, the kakapo has very little genetic diversity, even in immune genes. It is therefore at high risk of extinction due to infectious diseases,” explains the bioinformatician. “Probably due to climate change, newly hatched chicks are currently suffering from aspergillosis, an infection caused by the fungus Aspergillus.”

Lara Urban developed her mini-laboratory in New Zealand to study a disease in kakapo parrots. Photo: New Zealand Department of Conservation

Together with the gamekeepers, Lara Urban developed a fully portable analysis system consisting of a sequencing device, a battery, a box-shaped AI machine, a solar panel and a laptop. Using the system, they were able to test saliva samples from chicks in the wild and identify the pathogens they contained in two to three hours. “The gamekeepers can now detect particularly dangerous and highly virulent Aspergillus variants directly in the field and react in time,” says the scientist. “This example shows the great potential of the method: Endangered species can be monitored and protected against pathogens, and zoonoses that are dangerous to humans can also be detected at an early stage.”

Lara Urban with her team on the Helmholtz Pioneer Campus. Photo: Helmholtz Munich

In Munich, Lara Urban and her team are significantly expanding the range of applications for AI-assisted nanopore sequencing and want to test new approaches. For example, a promising study is already underway to monitor urban air quality and the impact of airborne pathogens on our health. Another project has already successfully demonstrated that nanopore sequencing can also be of great help in hospitals. Lara Urban's team was able to detect specific resistance genes in blood samples from patients with bacterial blood infections. In the future, hospital staff will be able to create a resistance profile in just a few hours and predict which antibiotics will help the patient and which will not. By contrast, the conventional method typically takes days and is often too slow for effective treatment.

“Our research shows that nanopore sequencing can massively improve the health of the planet,” explains Lara Urban. “The system is fast, portable, versatile and relatively inexpensive. That’s why – and this is particularly important to us – it can also contribute greatly to the democratization of science. Researchers in developing countries can also use the technology, making them less dependent on wealthy countries.”

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