Functional analysis of key targets of cyclic AMP signalling in malaria parasite invasion

David Baker (primary)
Infection Biology
London School of Hygiene & Tropical Medicine
Mike Blackman (secondary)
Malaria Biochemistry Laboratory
The Francis Crick Institute

Abstract

Malaria, caused by single-cell parasites of the genus Plasmodium, kills over 400,000 people each year. Despite intensive research, there remain many gaps in our understanding of malaria parasite biology. Our group focuses on understanding how signalling by a set of small molecules called cyclic nucleotides controls progression of the parasite life cycle, with the aim of developing new types of antimalarial drugs targeting this signalling pathway [1]. This project will use conditional mutagenesis combined with biochemical and cell biological approaches to dissect and further our understanding of the fascinating biology underpinning the complex life cycle of this important pathogen.


References

[1] Baker DA, Stewart LB, Large JM, Bowyer PW et al., (29 authors) (2017) A potent series targeting the malarial cGMP-dependent protein kinase clears infection and blocks transmission. Nat Commun. 8:430.

[2] Baker DA, Drought LG, Flueck C, Nofal SD, Patel A, Penzo M, Walker EM. (2017) Cyclic nucleotide signalling in malaria parasites. Open Biol. 7:170213. Review.

[3] Alam MM, Solyakov L, Bottrill AR, Flueck C, et al., (17 authors), Holder AA, Baker DA*, Tobin AB*. (2015) Phosphoproteomics reveals malaria parasite Protein Kinase G as a signalling hub regulating egress and invasion. Nat Commun. 6:7285.

[4] Flueck C, Drought LG, Jones A, Patel A, Perrin AJ, Walker EM, Nofal SD, Snijders AP, Blackman MJ, Baker DA. (2019)Phosphodiesterase beta is the master regulator of cAMP signalling during malaria parasite invasion.
PLoS Biology 17(2):e3000154.

[5] Patel A / Perrin AJ, Flynn HR, Bisson C, Withers Martinez C, Treeck M, Flueck C, Nicastro G, Martin SR, Ramos A, Gilberger TW, Snijders AP, Blackman MJ*, Baker DA*. (2019) Cyclic AMP signalling controls key components of malaria parasite host cell invasion machinery. PLoS Biology 17(5):e3000264.


BBSRC Area
Genes, development and STEM* approaches to biology
Area of Biology
Cell BiologyMicrobiology
Techniques & Approaches
BiochemistryBioinformaticsMicroscopy / ElectrophysiologyMolecular Biology