Functional analysis of the cGMP signalling pathway in malaria parasites: a master regulator of life cycle progression

This study will focus primarily on the role of cGMP signalling in blood-stage merozoite egress and erythrocyte invasion, but will also investigate the role of this pathway in gametocyte activation and gamete egress. The researchers will address questions ranging from what signals first activate the cGMP signalling pathway in the blood  stages and how these signals act to modulate cGMP levels, through to which cellular processes the pathway regulates and how this is achieved through interaction with other signalling pathways.With this study, researchers want to answer the following central questions: 1) What is the signal that activates the cGMP signalling pathway that leads to merozoite egress? How does the merozoite egress signal modulate cGMP levels and how does it differ from the known environmental signals required for gametocyte act ivation? 2) How is the parasite cGMP-dependent protein kinase (PKG) regulated, and how does this interact with the enzymes (guanylyl cyclases and phosphodiesterases) responsible for cGMP homeostasis? 3) Is the unique N-terminal P-type ATPase domain of the parasite guanylyl cyclase a functional aminophospholipid-transporting flippase and how does it regulate cGMP signalling? 4) How does cGMP signalling interact with cAMP signalling during parasite development? Does cGMP play an additional rol e in merozoite invasion of erythrocytes?

Wellcome Trust awarded grant details

Genetics and Genomics

Jul 2015 — Jun 2021

$989,437

United Kingdom