Advances in molecular genetic systems in malaria

Abstract

Robust tools for analysing gene function in Plasmodium parasites, which are the causative agents of malaria, are being developed at an accelerating rate. Two decades after genetic technologies for use in Plasmodium spp. were first described, a range of genetic tools are now available. These include conditional systems that can regulate gene expression at the genome, transcriptional or protein level, as well as more sophisticated tools for gene editing that use piggyBac transposases, integrases, zinc-finger nucleases or the CRISPR-Cas9 system. In this Review, we discuss the molecular genetic systems that are currently available for use in Plasmodium falciparum and Plasmodium berghei, and evaluate the advantages and limitations of these tools. We examine the insights that have been gained into the function of genes that are important during the blood stages of the parasites, which may help to guide the development and improvement of drug therapies and vaccines.

Plasmodium species: master renovators of their host cells

“…more than a decade ago, research on host cell remodelling by malaria parasites has proceeded rapidly, mainly owing to advances in genetic engineering and imaging technologies 98 . Molecular insights have revealed how the exportome of Plasmodium parasites facilitates survival in erythrocytes -host cells that are both metabolically limited and under constant surveillance by the spleen.…”

Calcium Builds Strong Host-Parasite Interactions

“…Furthermore, so far, only cultured parasites have been treated with auxin, and it remains to be seen whether the system works in mice or mosquitoes, given the relatively high concentration of auxin that seems to be required. The AID system has also been developed for P. falciparum (Kreidenweiss et al, 2013) and joins an increasing range of conditional knockout or knockdown systems that are now available for apicomplexan parasites, each with its own advantages and limitations (de Koning-Ward et al, 2015). A systematic head-to-head comparison of different conditional and inducible approaches on a larger set of genes would clearly be desirable and may soon become feasible in P. berghei, where barcoded alleles now allow the massive parallel phenotyping of large numbers of mutants in the same mouse (Gomes et al, 2015).…”

Gene drives and the management of agricultural pests

“…CRISPR-Cas9-based gene editing has already provided hope in the treatment of HIV (Kaminski et al 2016), as well as promised to offer a new generation of sickle-cell anemia, hemophilia and cancer treatments (Carroll 2014;Kannan and Ventura 2015;Liu et al 2016;Tang and Shrager 2016). It has shown potential ways to diminish the human suffering caused by malaria and other vector-borne diseases (Ghorbal et al 2014;de Koning-Ward, Gilson, and Crabb 2015;Hammond et al 2016), as well as impacted animal and plant breeding (Jenko et al 2015;Weeks, Spalding, and Yang 2016). In agriculture, gene editing may significantly improve gene drives used for pest control.…”