Dr Katerina Artavanis-Tsakonas

Our group studies ubiquitin and ubiquitin-like pathways in parasites with a particular focus on the malaria parasite, Plasmodium falciparum. Eukaryotes require ubiquitin for their own survival. Although this pathway is, to date, poorly characterized in eukaryotic parasites, it is axiomatic that Plasmodium uses ubiquitin and other ubiquitin-like (UBL) modifiers to regulate its physiology. Therefore, members of these parasitic pathways present interesting candidates for biological manipulation. We are using a combination of functional proteomics, genetics and crystallography to study ubiquitin and UBL-pathway components. Characterization of these pathways will shed light on ubiquitin processing in non-mammalian organisms and potentially uncover important targets to prevent Plasmodium infection and replication in humans.

As a parallel focus, we also study Trichinella spiralis. This parasitic nematode, selectively infects terminally differentiated skeletal muscle cells. This parasite does not destroy its host cell, but rather reprograms it to support its presence. Remarkably, through targeted protein secretions (ES), it is able to de-differentiate myotubes, initiating their re-entry into the cell cycle and subsequent re-arrest at the G2/M interface. Consequently, angiogenesis and collagen production are upregulated and host inflammatory responses are modulated. We aim to characterize these secretions to identify how individual parasite factors are capable of transforming terminally differentiated cells. Furthermore, we are interested in harnessing these parasite factors to not only better understand mammalian cell biology, but also to intentionally manipulate the fate of specific tissues.

• Exploring DUBs as novel antimalarial targets
• Defining the role of Cullin RING ligases in Plasmodium replication and differentiation
• Elucidating the Nedd8 pathway in Plasmodium
• Harnessing Trichinella effectors to regenerate muscle