Investigating the role of SCF ubiquitin ligases during sexual development of Plasmodium falciparum
To characterize the Skp, Cullin, F-box containing complex (SCF) complex during critical transitions of Plasmodium falciparum parasite development and assess whether their activity can be selectively inhibited to block transmission.
Ubiquitin and Nedd8 are involved in fundamental cellular processes and are essential to all eukaryotes. As such, enzymes mediating their dynamic attachment and removal from substrates present attractive targets for therapeutic intervention for both chronic and communicable diseases. Despite being evolutionarily conserved, differences in how these pathways are controlled in higher and lower eukaryotes do exist and could potentially be exploited to generate pathogen-specific inhibitors. It is, therefore, necessary to understand the cell biological mechanisms behind how these pathways are regulated. The SCF complex comprises a group of multi-subunit enzymes that catalyse ligation of ubiquitin onto substrate proteins. The role of these ligases in controlling cell-cycle progression in eukaryotes is well-established, however neither their composition nor function have been studied in the malaria parasite, Plasmodium. This work will help define novel targets for the development of control strategies aimed at reducing both the clinical pathology of infected individuals and the number of malaria cases at the population level.