Miguel Soares and his team at GIMM receive EUR 2.5 million from the European Research Council to pursue one of biology’s most counterintuitive hypotheses: that the molecule behind jaundice may be one of our oldest defences against malaria.

For 2,500 years, physicians have read jaundice as a warning sign. The yellowing of skin and eyes caused by rising bilirubin levels has been treated as evidence that something is going wrong. Miguel Soares has spent years building a case that, in certain situations, the opposite is true: that the body is not failing, but fighting.

His new project, KILLBILL (A metabolic-based defence strategy against malaria), funded by an ERC Advanced Grant worth EUR 2.5 million, will put that idea to the test over the next five years. The team will map the multiple ways bilirubin may act during malaria infection: as a weapon against the parasite, as a shield for the host’s tissues, and as a potential modulator of immune responses and vaccine efficacy. The results could reframe how we think about one of humanity’s oldest diseases.

The hypothesis is not speculative. Work from Soares’s laboratory, published in Science (see reference 1) and iScience (see reference 2), has already shown that bilirubin accumulation during malaria infection may be an adaptive response rather than a byproduct of disease. The body, it appears, may be deliberately raising its own bilirubin levels to limit the spread of the parasite and reduce collateral damage to its tissues.

“For 2,500 years, jaundice has been described as a sign of disease. What we have shown is exactly the opposite: it is protection,” says Miguel Soares. “This is a true paradigm shift.”

The European Research Council Advanced Grant is awarded exclusively to established researchers who have demonstrated the ability to produce ground-breaking science. Competition is intense: the programme funds only a small fraction of applications each year, selecting projects that reviewers judge to represent a genuine leap rather than an incremental step. For Miguel Soares, this is the second ERC Advanced Grant of his career, a distinction shared by very few scientists in Europe and a mark of sustained excellence that is rare in any field.

The grant also reflects the environment that makes such research possible. GIMM was built precisely to bring together the range of expertise that a project like KILLBILL demands: deep knowledge in immunology, parasite biology, haem metabolism, tissue injury and repair, and the translational pathways that can carry a laboratory finding toward clinical use. That combination, assembled under one roof and anchored in a culture of scientific rigour, is what makes it credible to ask questions as fundamental as these.

KILLBILL also opens a window onto the long-observed, poorly understood connection between malaria and sickle cell disease. Sickle cell trait is known to confer partial protection against malaria, a relationship previously documented by Soares’s team (see reference 3). The working hypothesis now is that bilirubin sits at the centre of both phenomena: limiting the parasite’s reach while simultaneously dampening the cellular damage it causes.

“We have strong evidence that bilirubin may be doing both things simultaneously,” says Miguel Soares. “Protecting against the parasite and protecting the organism’s tissues.”

If KILLBILL delivers on its promise, the implications extend beyond malaria. A molecule as ancient and widespread as bilirubin, deployed by the body as a front-line defence, could inspire a new class of therapies rooted not in pharmacology but in evolution itself. For sickle cell disease, for iron-related tissue damage, and for infectious diseases more broadly, the work beginning now at GIMM may prove more consequential than its starting point suggests.

References:
Reference 1 here.
Reference 2 here.
Reference 3 here.