Hugo Belda

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The essential host genome for Cryptosporidium survival exposes metabolic dependencies that can be leveraged for treatment An arrayed microscopy-based CRISPR screen revealed host genes affecting multiple infection phenotypes of the intracellular parasite Cryptosporidium. Hits in the host cholesterol biosynthesis pathway a...

Our paper has finally graduated from pre-print to peer-reviewed, pretty much unscathed, and is out now! www.cell.com/cell/fulltex...

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!

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

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

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!

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

The fast-evolving FIKK kinase family of Plasmodium falciparum can be inhibited by a single compound - Nature Microbiology FIKK effector kinases underwent rapid evolutionary expansion and are a druggable target in Plasmodium falciparum.

Better late than never, but I am thrilled to share our newest research from the Treeck lab!!! www.nature.com/articles/s41...