BVRA generates bilirubin from biliverdin. It also moonlights as a kinase and transcription factor.
To isolate its enzymatic role, we made two mutant lines: BlvraG17A (~95% activity loss) and BlvraE97A (~80-90% loss), targeting the NAD(P)H-binding and reductase motifs.
Bilirubin exerts major protective effects on the host, beyond its direct anti-plasmodial activity (science.org/doi/10.1126/science.adq6741).
Big plans ahead for the yellow guardian against malaria. If interested, send an email to: [email protected]
Infected with Plasmodium chabaudi, both mutant strains succumbed. Wild-type controls survived.
The critical observation: mutants failed to reach circulating bilirubin levels of ~20-30 μM (~1-2 mg/dL). Below that threshold, no parasite control, no resolution.
This defines a quantitative bilirubin threshold for malaria protection, with direct implications for therapeutic development and biomarker-guided strategies.
🙏 Thanks @gimmfoundation.bsky.social, @miguelmmesquita.bsky.social for TWO knock-ins, Moisés Mallo for mouse genetics wizardry, Ana Nóvoa for golden hands, Ana Figueiredo for discovering bilirubin's antimalarial effect & support.
🧬 New findings from our lab @gimminstitute.bsky.social, out in iScience, led by PhD student Miguel Mesquita who defends his thesis very soon!
We define a bilirubin threshold for malaria protection using catalytically deficient BVRA mouse mutants.
🔗 doi.org/10.1016/j.isci.2026.115958
Applications are open for the Master in Biomedical Research (MIB)! Hands-on training at GIMM & FMUL. Cancer Biology, Neurosciences, Cardiovascular, Infection & Immunity. English-taught. Deadline: May 31. (@gimminstitute.bsky.social)
Please share!
medicina.ulisboa.pt/en/biomedical-research
Miguel Soares
Miguel Soares
Miguel Soares
Miguel Soares
Miguel Soares
🎟️Do you want to be part of a dynamic platform for dialogue and discovery?
Register your Early Bird acess for GIMM Festival 2026, taking place 17–19 September in Lisbon, and hear from Charles Rice, Yasmine Belkaid and many others speakers.
🔗Register now: linktr.ee/gimm_institute
Miguel Soares
Miguel Soares
GIMM Institute
An American leader who believes in science.
Christopher Hale
Red blood cells don't always make their own heme - under stress, they scavange it from neighbors. Our new paper in @ScienceMagazine reveals a cell-nonautonomous heme acquisition pathway essential for erythroid hemoglobinization. #heme #erythropoiesis #anemia
www.science.org/doi/10.1126/...
www.science.org
Heme, an iron-containing cofactor, is synthesized in mitochondria by an eight-enzyme pathway. Although cells were thought to manage heme autonomously, more than 1000 proteins contribute to its product...
