Abstract
Malaria kills over 400,000 people every year and is caused by single-cell parasites of the genus Plasmodium. Our understanding of malaria parasite biology is relatively poor; with the majority of the parasites genes uncharacterised. Our group focuses on understanding how an intracellular signalling pathway utilising cyclic nucleotides controls progression of the parasite lifecycle, with the aim of developing new antimalarial drugs targeting this pathway [1]. This project will study cyclic nucleotide-regulated parasite egress and invasion processes by conditional gene deletion utilisng CRISPR Cas9 mutagenesis, combined with biochemical, cell biological and imaging approaches.
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] Balestra AC, Koussis K, et al., [19 authors] Baker DA, Blackman MJ, Brochet M. [2021]
Ca2+ signals critical for egress and gametogenesis in malaria parasites depend on a multipass membrane protein that interacts with PKG. Sci Adv. 2021 Mar 24;7[13]:eabe5396.
[5] 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.
[6] 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.