Imitating nature: studying ticks for cardiovascular diseases

Inaugural lecture Ingrid Dijkgraaf

Ticks, blood-sucking moths and venomous snakes: most people think they are scary, but these animals are incredibly useful when studying cardiovascular diseases. This is exactly what Ingrid Dijkgraaf does at the Cardiovascular Research Institute Maastricht (CARIM): she investigates the substances these animals produce and what we can learn from them. Her focus is on making plaque in arteries visible. She has been appointed professor of biomimetic chemistry and delivered her inaugural lecture on March 22 2024, titled 'Chemical innovation through biological inspiration'.

During her postdoc at CARIM, Ingrid researched unstable plaques. “When your blood vessels become fatty, a layer of fat and inflammation forms in the vessel wall. This is called plaque,” she explains. “Some plaques are stable, others are dangerous. They can rupture, after which their contents come into contact with your blood. This causes an acute blood clot, which can lead to a heart attack or stroke. In our research, we investigated how we could make these unstable plaques visible in mice."

Lego bricks

Before this, Ingrid conducted research on proteins. “Plaque in the arteries is actually a type of inflammation, so various inflammatory proteins are involved,” she explains. “We recreated these by linking amino acids together like Lego bricks. The only problem was that it was difficult to make these proteins visible, because they naturally occur in your body as well. That was not ideal for this research.'"

Together with her colleague Pieter van de Vijver, she delved into the literature. “We found that ticks, the blood-sucking parasites, produce proteins that can deactivate inflammatory proteins,” she says. “These are completely different proteins which are not naturally present in the human body. We recreated these proteins and investigated how we could use them to visualise plaque.”

Ticks

The tick research then took a life of its own, according to Ingrid. “We are currently studying how ticks use their own substances to deactivate inflammatory proteins, but also how they stop blood clotting. Tick proteins bind to platelets to prevent blood clotting when they bite someone. This suppresses the activity of platelets and blood proteins. A tick can remain attached to your skin for days without causing inflammation. In Lyme disease, a ring forms, but the bite mark itself does not turn red or itch. There are fascinating substances in ticks that we can learn a great deal from. Slowly, other research groups are emerging which are looking at blood-sucking parasites. One group, for example, is researching blood-sucking moths. I did not even know those existed.”

Biomimetics

Ingrid’s inaugural lecture was titled “Chemical Innovation through biological inspiration”. She has been appointed professor of biomimetic chemistry, which is also the title of her chair. “Biomimetic chemistry, or biomimetics for short, consists of two words: ‘bios,’ meaning life, and ‘mimesis,’ meaning imitation,” Ingrid explains. “This means imitating nature. What can we use and how can we adapt it for human health?”

There are many examples of biomimetics, for example in chemistry and biomedical science, but also in construction. “The Eastgate Centre is a building in Zimbabwe without air conditioning. Yet, the temperature inside is comfortable almost all year round,” says Ingrid. “This is due to its ventilation system, which is based on the design of termite mounds. These mounds are exposed to the blazing African sun all day, but they remain relatively cool inside. Termites have created special tunnels that allow the mound to ventilate well and let the hot air go straight out. The Zimbabwean building is inspired by this, and it works incredibly well. And so there are several examples. NANO tape, a double-sided tape with strong adhesive properties, was copied from gecko feet. The Japanese high-speed train is designed to reach high speeds with minimal resistance, and its design was inspired by kingfisher beaks.”

Frog skin

Similarly, Ingrid is now looking at ticks. “When a tick bites you, your body responds immediately, sending various immune cells and inflammatory proteins to the area,” she explains. “Of course, the tick does not like that, as it wants to stay attached for as long as possible. Therefore, your body’s reaction must be suppressed. The tick secretes its own substances to stop blood clotting and prevent your inflammatory proteins from going towards it. We are trying to mimic these proteins, but also improve them. Sometimes they are very large, which is not useful to us. If we can pinpoint the active part of the protein, we can make it smaller. This is not only cheaper, but also provides other benefits. Smaller proteins get to the right place faster and do not circulate as long. We aim to optimise the proteins for our use, but we do not want to surpass nature.”

Besides ticks, Ingrid is also working with frogs and snakes. “Frog skin has certain substances on it that, similar to ticks, stop blood clotting. Snake venom contains these substances too, as it makes it easier for them to digest their prey,” Ingrid explains. “I also hope we will soon be able to do something with those blood-sucking moths.”

Vaccines

The goal of Ingrid’s research is to make unstable plaques visible earlier, leading to better diagnosis. “With MRI and CT scans, you can already see if a plaque is unstable, but that is often at a late stage,” Ingrid says. “In surgery, you can remove plaque material and look under a microscope to see how many inflammatory cells are present, but obviously that procedure is very invasive. We want to catch it earlier, so we can offer better treatment and avoid using aggressive therapies. This reduces time and suffering for the patient. For example, people often have to take blood thinners for long periods. If we can make those plaques visible earlier, people can adjust their eating habits or exercise more. Now we are investigating which inflammatory proteins we need to deactivate exactly. After all, some of these proteins are in fact useful, as they help your immune system function properly.”

Meanwhile, Ingrid is also collaborating with Lyme disease experts. “We are trying to develop anti-tick vaccines. This does not quite fit within CARIM’s scope, but with the knowledge we gain, we might be able to develop an anti-plaque vaccine in the future.”

Learning from nature

When does Ingrid consider her research successful? “When I can translate it to the clinic, and we can help patients with what we discover,” she says. “I may be demanding, but that is because of my background in nuclear medicine. During my time as a PhD student and postdoc, I created two tracers. These are radioactive molecules used in PET and SPECT scans to make diseases visible. These tracers are now being used in clinical practice. So, that ambition is certainly there.”

In addition, Ingrid hopes that people realise we can learn a lot from nature. “And that we should therefore take care of nature,” she adds. “Ticks, blood-sucking moths and snakes are scary, but also useful. We can only look to them for inspiration, as they have been here for millions of years – longer than we humans have.”

 

Text: Joëlle van Wissen
Interview: Toñita Perea y Monsuwé
Photo: Joey Roberts

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