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Reposted by Hugo Belda

Melissa Hart @melissa-natalie.bsky.social · 28/01/2026

Excited about parasites? Love watching movies? Come join our Wellcome-funded project! Parasitology friends, please do share far and wide.

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Hugo Belda @hbelda.bsky.social · 23/06/2025

Huge thanks to all collaborators, especially David Bradley, Evangelos Christodoulou & Dhira Joshi for their invaluable contributions. Thanks to @moritztreeck.bsky.social & @crick.ac.uk ac.uk for the support. Stay tuned—more on FIKK kinases coming from the Treeck lab at @gimmfoundation.bsky.social!

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Hugo Belda @hbelda.bsky.social · 23/06/2025

We collaborated with the Crick-GSK LinkLabs to screen for inhibitors targeting multiple FIKKs via their conserved domains. Several pan-FIKK inhibitors were found, one shown to block FIKK activity in malaria-infected cells. We now aim to optimise these compounds

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Hugo Belda @hbelda.bsky.social · 23/06/2025

Using an FIKK13 crystal structure and AlphaFold2 models, we identified two residues that determine substrate specificity. Mutating these residues in FIKK12 switched its motif from acidophilic to basophilic. Their location in fast-evolving loops may explain FIKK substrate diversity

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Hugo Belda @hbelda.bsky.social · 23/06/2025

We expressed most FIKK kinase domains and used random peptide libraries to define their phosphorylation motifs. Most were serine/threonine kinases with distinct preferences, highlighting specificity. Strikingly, FIKK13 evolved into a tyrosine kinase, an unusual feature in unicellular parasites!

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Hugo Belda @hbelda.bsky.social · 23/06/2025

P. falciparum, the parasite behind malaria’s deadliest form, expresses an expanded FIKK kinase family. Despite conserved domains and some overlapping expression and localisation, analysis of field isolates showed 18 out of 21 lack inactivating mutations, indicating distinct and essential functions

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