Clusters of malaria parasites growing inside human red blood cells.

Mike Blackman : cGMP-mediated signalling in regulation of malarial egress

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Relatively recent work from this laboratory, in collaboration with David Baker's laboratory at the London School of Hygiene & Tropical Medicine, has shown that discharge of SUB1 into the parasitophorous vacuole is regulated by the cyclic nucleotide second messenger cyclic GMP (cGMP), through its activation of a single parasite protein kinase called PKG (Collins et al., 2013a). Selective inhibitors of PKG reversibly block egress, whilst pharmacological agents that artificially upregulate cGMP levels in the parasite can induce premature egress (Collins et al., 2013a; Taylor et al.,2010).

We are currently working with David Baker to further dissect the regulation of the cGMP pathway that controls egress using conditional gene disruption (Collins et al., 2013b), new pharmacological tools, metabolomics and heterologous protein expression.

 PKG regulates release of SUB1 and egress

Figure 1: PKG regulates release of SUB1 and egress