UC Riverside nematologist receives NIH award for studying parasite-host interactions

UC Riverside nematologist receives NIH award for studying parasite-host interactions

To study how parasites evolve to break through their hosts' defenses, the National Institutes of Health awarded UC Riverside nematologist Simon "Niels" Groen a $1.9 million Outstanding Investigator Award.

Roundworm parasites infect people, livestock and crops. Insights into why certain worms can evade host immune protection could help prevent a ticking time bomb: the declining effectiveness of pesticides and antibiotics against infections.

The resistance of bacteria, fungi and parasites to drugs and pesticides makes it more difficult and sometimes impossible to treat common infections such as pneumonia and tuberculosis in humans, as well as pest infestations in crops. International health authorities warn that without urgent action, we are heading towards a future where minor injuries and infections can be fatal. Plant and animal production will also face increasing hurdles.

When roundworms infect humans, animals, or plants, they begin injecting proteins from their saliva into host cells to suppress the immune response. These processes are quite similar across hosts, allowing us to study coevolutionary arms races between plants and parasitic worms and draw conclusions about the evolution of worm infections in humans.”

Simon “Niels” Groen, a nematologist at UC Riverside

Over the next five years, Groen will use the funds to conduct a study in two parts. The first part of the project will study hundreds of tomato and rice plants, both those grown on farms and those growing in the wild. These are not plants artificially bred to achieve immunity. However, Groen assumes that many of them have developed defenses against infectious roundworms, also known as nematodes.

“These plants are a natural laboratory in which we can link their genes and chemical properties of their roots to their resistance to worm infections,” Groen said.

"We will learn about the molecular mechanisms by which plants defend themselves. This includes the production of defense chemicals, some of which could be used as novel drugs or antibiotics in humans and livestock," said Groen. “We can then share this information with biomedical researchers and plant breeders.”

This aspect of the project will also help increase food security, particularly in parts of Africa and Asia where nematodes are a problem for farmers. Much research has been done on above-ground insect pests, but less research has been conducted below ground, where nematode infections affect economically important crops.

"Nematodes are the most devastating threat to soybeans. In rice and tomatoes, nematodes can cause yield losses of up to 20%. That's a lot of people going without food," Groen said.

In the second part of the project, the research team will address the nematode side of the equation. “How do they evolve to break the plants’ resistance?” Groen asked.

In tomatoes, there is a gene, Mi-1, that monitors the inside of plant cells for incoming attacks. In a way that is not yet fully understood, this gene senses something about impending nematode infections that triggers an effective immune response.

Mi-1 was discovered in wild tomatoes in the 1940s and has since been bred in California tomato processing plants to keep away nematodes. Groen explained that this breeding scheme subjects root-knot nematodes to enormous natural selection pressure to overcome the resistance conferred by the gene.

But more and more farmers are finding nematodes in their supposedly resistant tomato crops. "We don't understand how they broke the resistance. Is there one way or multiple ways they were able to do this? We're going to try to figure out how many ways there are to skin a cat from a nematode's perspective," Groen said.

Thanks to UC Extension specialists, Groen's team will be able to compare the genes of worms collected before resistance became more common, as well as the genes of worms that managed to overcome the plant's immune barriers.

One hypothesis is that when the nematode penetrates the plant, it uses its saliva to inject proteins that have different targets in the host cell. When Mi-1, which is floating around in the cell, encounters one of these nematode proteins, it triggers an immune response that kills the worm. However, when the worm stops injecting this protein, Mi-1 does not know that the invader has arrived.

There are receptor proteins such as Mi-1 that have evolved similarly in humans and monitor cells for incoming attacks, as well as additional molecular processes that are similar to each other in humans and plants. However, from an ethical and logistical perspective when studying human infections, it makes sense to begin this research with plants and nematodes.

"The worms are just a model system to study the elimination of resistance. But they could still help us find new solutions to pesticide and antibiotic resistance," said Groen.

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