The fight against malaria requires deeper knowledge of the parasite's life cycle

Malaria is one of the most severe parasitic diseases and a critical global health issue. It affects millions of people every year and causes hundreds of thousands of deaths, especially among children under the age of five. The development of new drugs and effective vaccines against malaria depends on obtaining a deep understanding of the biology of the malaria parasite, a challenge to which Oliver Billker has dedicated his research career.

It turned out there is a small molecule unique to mosquitos that the parasite can perceive and respond to. Basically, you could say that the parasite smells the mosquito.

Oliver Billker’s fascination with parasites began when he studied biology in Berlin. Trained in classical zoology, he became curious of the lifecycle of parasites; how they navigate through their hosts and how such complex interactions could have evolved.

“Malaria parasites are very well adapted to different tissues in their human hosts and in the mosquitoes that transmit them. They are guided through their life cycle by communicating with these environments. It is this complexity in the interplay between the parasite, the host and its immune response that I have always found interesting,” says Oliver Billker.

Knowledge of molecular events

During his PhD at Imperial College London he was given the task to determine how the parasites recognise that they have been taken up by a blood-feeding mosquito.

“It turned out there is a small molecule unique to mosquitos that the parasite can perceive and respond to. Basically, you could say that the parasite smells the mosquito, and that triggers all the developmental processes that we are now studying in the lab. Since my PhD, where I worked out what that basic first interaction is, we’ve really obtained a much more detailed picture of many of the molecular events that happen within the parasite to turn recognition of the mosquito into a developmental response,” he says.

Oliver Billker has been doing research at Umeå University since 2018. He was attracted by the strong and collaborative research environment in infection research and microbiology, as well as its international connections through The Laboratory for Molecular Infection Medicine Sweden (MIMS) of which he is now the director.

In the laboratory, Oliver Billker’s research team uses a rodent model of the malaria parasite that infects mice instead of humans, allowing them to safely transmit the parasite to mosquitos and study it efficiently. Thanks to genetic tools they have developed, they can now systematically discover the functions of the parasite’s approximately 5000 genes during its life cycle. This has been a major breakthrough in malaria research.

“We no longer study one gene at a time. Instead, we take a biological question, like ‘How does the parasite prepare to be transmitted to the mosquito?’, and get an answer that includes most genes involved in that process.”

Planning new collaborations

Using these tools, Oliver Billker is beginning to ask more and more challenging questions. He plans to collaborate with insect researchers to delve deeper into the interaction between the parasite and the mosquito, aiming to understand what affects a mosquito’s ability to transmit malaria parasites and which aspects of the parasite's biology determine the mosquito species capable of transmitting malaria.

“The life cycle stages that we are now interested in have two copies of each gene. We have just worked out a way to disrupt not just one but both copies.  This opens up new ways to find out what these genes do,” says Oliver Billker.

Recently, Oliver Billker was awarded the Axel Hirsch prize from the Karolinska Institute and was admitted to the prestigious Wallenberg Scholars programme.

“I was delighted. The Wallenberg Scholars programme provides long term funding at a generous level that is very flexible. I feel very encouraged to use this funding to move in what I think is the best and most important direction for our research.”

What are the main challenges in your research field right now?

“There is clearly a need for better vaccines and drugs that can achieve certain things, like curing an infected person with a single dose or blocking transmission. Another challenge is insecticide resistance in mosquitos that is now spreading. In terms of basic research, there remain enormous challenges for many of the human parasites of culturing certain life cycle stages to find new drugs and having genetic systems to investigate them effectively.

Where will you be 10 years from now?

“I very much hope that we will have put together an international group of collaborating laboratories with malaria geneticists, entomologists, modelers, and mathematicians that together will better understand what factors determine the reproductive rate of malaria. Hopefully we can use this knowledge to come up with new intervention strategies and predict how changing mosquito populations, possibly as a result of climate change, will affect malaria transmission in different regions. I also expect that some of the insights we generate will help us understand how mosquitoes spread other pathogens, including viruses, which are spreading beyond the tropics.

Our research could lead to vaccines and drugs that target the transmission of the parasites.

How far away is a vaccine that could stop this disease for good?

“I think we will have to be prepared to make progress in small steps. We now have two licensed vaccines as part of our armory to control malaria together with insecticides, bed nets and drugs, but they are not a silver bullet. Their efficiency is 60 to 70 percent within a season after a number of doses. But there are other concepts to come up with vaccines that could be very efficient. Our research could lead to vaccines and drugs that target the transmission of the parasites. They don’t help the infected individual but prevent them from passing the infection on to mosquitos.

What are your driving forces? What keeps you going when you struggle with your research?

“There are two answers. First, I just love new data. I love to look at them and try to understand the biology of the system. I also get a big kick out of seeing scientists in my lab ask bright questions and advance their careers. I find the team approach to science incredibly satisfying, extending beyond my own team. I love when progress comes from a group that is more than the sum of its part, distilling insights none of us could achieve alone.