Investigating the role of SCF ubiquitin ligases during sexual development of Plasmodium falciparum

泛素和Nedd8参与基本的细胞过程，对所有真核生物都是必不可少的。因此，调节其动态附着和从底物上移除的酶为慢性和传染性疾病的治疗干预提供了有吸引力的靶点。尽管这些途径在进化上是保守的，但在高等和低等真核生物中，这些途径的控制方式确实存在差异，并有可能被利用来产生病原体特异性抑制物。因此，有必要了解这些途径背后的细胞生物学机制。SCF复合体由一组多亚单位酶组成，催化泛素连接到底物蛋白上。这些连接酶在真核生物中控制细胞周期进程的作用是众所周知的，然而它们的组成和功能在疟疾寄生虫疟疾中还没有被研究过。我们的目标是在恶性疟原虫发育的关键转变过程中表征SCF复合体，并评估它们的活性是否可以被选择性地抑制以阻断传播。通过这项工作，我们希望为制定控制战略确定新的目标，旨在减少感染者的临床病理和人口层面的疟疾病例数量。

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. We aim to characterize the SCF complex during critical transitions of Plasmodium falciparum parasite development and assess whether their activity can be selectively inhibited to block transmission. Through this work, we hope to 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.