Rajagopal Murugan received ERC Starting Grant to investigate the quiet saboteurs of global health

This question is especially urgent for diseases like malaria. Promising new malaria vaccines are being developed, but in many regions where malaria is common, helminths are also widespread. That overlap could reduce how well these vaccines work. In other words, the very places that need malaria vaccines most may also be the places where those vaccines are least effective. Murugan hopes to understand this problem at the molecular level, so we can design vaccines that work better for everyone.

One of the key questions Murugan will ask is: do worms lower the bar for B cell selection? In a healthy immune response, only the best-fitting B cells are chosen to make antibodies. But helminths may create a “regulatory” environment that allows weaker B cells to slip through, resulting in less effective immunity. Murugan plans to pinpoint exactly where this process breaks down: during B cell activation, selection, memory formation, or recall and find ways to restore it.

To investigate this, Murugan will combine cutting-edge lab techniques with unique clinical studies in his ERC-funded project, called B-SELECT. In one study, Dutch volunteers will be deliberately infected with the parasite Schistosoma mansoni under controlled conditions. This will allow Murugan to track how B cells respond to the parasite over time. In another study, he will compare vaccine responses in Ugandan residents who live in worm-endemic areas with those who don’t. The goal is to find out how worm infections affect the quality of antibodies produced after vaccination.

He will use a powerful “multi-omics” platform to study B cells at the single-cell level. This means he will measure not just which antigens the cells recognize, but also their genetic makeup, surface markers, and how well their antibodies bind to targets. He will also work with transgenic mice and human tonsil organoids—miniature immune systems grown in the lab—to explore the underlying mechanisms and test ways to reverse the effects of helminth-induced immune suppression.

Ultimately, Murugan hopes to build a toolkit for rescuing vaccine responses in populations affected by helminths. His ERC proposal lays the foundation for a new chapter in immunology, one that takes into account the hidden influence of parasites on global health.