Functional analysis of the downstream mediators of cyclic nucleotide signalling in malaria parasites

This research programme will deliver mechanistic understanding of how cyclic nucleotide signalling controls the development of two key phases of the malaria parasite lifecycle: the asexual blood stage that causes pathology, and gametogenesis that is required for transmission to the mosquito vector. The researchers at LSHTM have previously shown that there is a temporal switch from cyclic GMP (cGMP) signalling to cAMP signalling as the asexual parasite progresses from egress (escape from its host erythrocyte) to invasion. Cyclic GMP signalling also controls egress of sexual stage parasites to enable fertilisation in the mosquito. In both lifecycle phases, egress requires cGMP-dependent calcium flux. Researchers have recently identified a unique, essential membrane-bound binding partner of the cGMP-dependent protein kinase (PKG). They have also identified a set of high confidence targets of cAMP signalling required for invasion and subsequent parasite development, and have obtained exciting new insights into how cGMP production is governed.

Wellcome Trust awarded grant details

Basic Science

Jul 2021 — Jun 2025

$958,437

United Kingdom