dentify relevant interacting proteins and novel candidates in signal transduction cascades. Acknowledgements This work was supported by the Netherlands Organization for Scientific Research, Grant No. 014-80-008. We thank R. Barstead for kindly providing the cDNA library, P. Sengupta for kindly providing the nhr-22 mutant strain, and the Caenorhabditis Genetics Stock Center for providing some of the strains used in this study. Recent reviews have concluded that in order to have a sustainable impact on the global burden of malaria, it is essential that we knowingly reduce the global incidence of infected persons. To achieve this we must reduce the basic reproductive rate of the parasites to < 1 in diverse epidemiological settings. This can be achieved by impacting Received 8 October, 2014; revised 12 December, 2014; accepted 24 December, 2014. For correspondence. E-mail r.sinden@ imperial.ac.uk; Tel. 617619; Fax 617608. 2014 The Author. Cellular Microbiology published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. cellular microbiology 452 R. E. Sinden Human Mosquito Zygote Ookinete Oocyst I II III IV Gametocyte development V Infectious Gamete formation Fertilization Fig. 1. Some of the earlier and significant steps in the analysis of the cell biology of sexual development of Plasmodium spp. I Light microscopy 1881Induction mechanisms 1926II III IV V Gamete formation Fertilization Ookinete Oocyst Electron microscopy 1965Nuclear organization 1973Transcriptome 2000Translation repression 1990Proteins first identified 1974Proteome 2005Metabolome 2014- Vermeulen et al., 1985) the red blood cell infected by the elongated immature P. falciparum gametocyte, and surfin expression on the infected RBC, might correlate with retention of the immature gametocyte in the complex extravascular environment of the bone marrow. The former attribute is unlikely to apply to the spherical parasites of the subgenus Plasmodium that lack the elongate sub-pellicular cytoskeleton of Laverania. When considering induction of gametocytogenesis in the peripheral blood, current in vitro evidence suggests that in P. falciparum induction occurs in the trophozoite of the asexual generation preceding gametocyte formation, and that the merozoites from any one committed schizont are predetermined to be either male or female . A marker of this commitment has recently been described as Pf10_0164 PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19822663 . In the rodent malaria parasite P. berghei gametocyte determination possibly occurs following invasion by the merozoite. Myriad potential external inducers of gametocytogenesis have been described, all of which may be broadly classified as `stress related’, but molecular characterization of any consensus induction pathway still eludes us. order LOXO 101 Future 
experiments to understand sexual/asexual differentiation should at least entertain the hypothesis that sexual development is the ancestral and therefore default pathway. Not knowing the molecular properties of the inducers, it is unsurprising that we do not know the receptors initiating the signalling pathways for gametocytogenesis. Things we do know however are that the down-regulation of the histone deacetylase gene pfHda2, the heterochromatin 2014 The Author. Cellular Microbiology published by John Wiley & Sons