Sigala Lab


Malaria is an ancient scourge of humanity and one of the deadliest infectious diseases worldwide. High-throughput genomics has greatly improved our knowledge of the malaria parasite, Plasmodium falciparum, but functional and mechanistic understanding of the proteins and metabolic pathways encoded by the parasite’s highly divergent genome has lagged far behind. All clinical symptoms of malaria arise during parasite infection of erythrocytes, and this developmental stage can be readily cultured in vitro to enable in-depth study of the molecular factors and cellular features that equip Plasmodium parasites to survive and proliferate within host erythrocytes.

Our research has two general goals:

1) To develop and apply diverse cellular, genetic, and biochemical tools to uncover general metabolic principles and adaptations governing the unique biology of P. falciparum parasites during infection of human red blood cells.

2) To apply this knowledge to develop novel strategies to target this virulent pathogen.

Our work is highly interdisciplinary and spans multiple areas of cell biology, genetics, chemical biology, protein biochemistry, and biophysics. We use CRISPR/Cas9-based genome editing to tag endogenous parasite proteins for localization and trafficking studies and for conditional regulation of protein expression in blood-stage parasites. We exploit the power of in vitro biochemistry to interrogate the functional properties of purified proteins and reconstituted biochemical pathways. As appropriate, we also carry out parallel studies in bacteria and yeast or mammalian cells to develop tools and to compare and contrast general metabolic principles in discrete prokaryotic and eukaryotic organisms. (Continued on the Research page...)