London School of Hygiene and Tropical Medicine, United Kingdom
Apical membrane antigen-1 (AMA1) is a protein from the surface of invasive forms of the malaria parasite and it is required for parasitic invasion of red blood cells (RBCs). AMA1 spans the parasite cell membrane and a part of it – the cytoplasmic domain (CD) – is inside the cell. The AMA1 CD has an essential role in invasion and is modified through a process called phosphorylation, typically associated with the transduction of signals within cells. I hypothesise that when the external portion of AMA1 contacts an RBC, the CD transmits a signal to the parasite. I want to understand how this signal is produced and how the parasite responds to the signal.
I will modify the AMA1 CD to examine how this affects signalling to the parasite, and to identify other parasite proteins that interact with it. These parasite proteins will then be studied for their importance when invading a host cell.
A greater understanding of the mechanism behind host cell invasion will help identify novel therapeutic targets for the prevention of malaria.