Dr Samantha Emery - Population Health and Immunity division

Dr Samantha Emery - Population Health and Immunity division

Location: 
Davis Auditorium
Start Time: 
Wed, 12/06/2019 - 1:00pm
End Time: 
Wed, 12/06/2019 - 2:00pm

​Use it or lose it – first insights into protein methylation and transferases in Giardia parasites

Wednesday seminar

Protein methylation coordinates epigenetic gene expression and drives cell development. Methyltransferase enzymes methylating lysine and arginine and represent prime drug targets to interfere with life cycle progression in Giardia— the most common gastrointestinal parasite of humans. Resistance to limited drug classes is a pressing problem in Giardia control, and new avenues for inhibiting the parasite’s life cycle are required.

To understand the methylation system in Giardia, Dr Samantha Emery has combined detailed bioinformatic curation with high-content drug screening and deep untargeted proteomics. This has revealed a reduced methyltransferase cohort in the parasite, and the presence of a conserved lysine-methylation network. Dr Emery bioinformatically curated the complement of Giardia’s methyltransferases to identify a reduced cohort in number, as well as structural and functional classes. In particular this highlighted the striking absence of arginine methylation enzymes, substrate motifs and methylarginine residues in the parasite, both bioinformatically and experimentally in vitro.

In contrast, the minimized cohort of lysine methyltransferases identified by Dr Emery manage and coordinate methylation at over 300 sites, revealed via high-resolution MS and novel database searching strategies. Excitingly, Dr Emery’s high-content screening assays identified several lysine methyltransferase inhibitors that disrupt models of parasite transmission and virulence, and she has explored these models using quantitative proteomics. Together these data demonstrate the intricacies of protein methylation networks in this basal eukaryote, and provide intriguing clues to the evolution of these post-translational signalling networks in humans and higher eukaryotes.