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The molecular mechanisms of sex determination in a malaria parasite

Project description

Sexual reproduction of the malaria parasite

Transmission of the Plasmodium parasite, the causative agent of malaria, to a new host requires sexual reproduction in the mosquito. Recent evidence indicates that sexual development involves a small panel of genes that regulate the sex ratio, an adaptive trait paramount for transmission success in response to different conditions. The EU-funded MalariaSex project will investigate the function of these genes and their underlying mechanisms. The identification of the molecular mechanisms responsible for Plasmodium sexual development will shed light on the regulation of life cycle decisions and facilitate the design of interventions that block transmission.


Sexual reproduction is an obligate stage in the complex life cycle of Plasmodium parasites, the causative agent of malaria. While cyclic asexual replication of the parasite in the vertebrate host is associated with all clinical symptoms of malaria, transmission of the disease to a new host relies on sexual reproduction of the parasite in the mosquito. Transmission and reproductive success depend on the ability of malaria parasites to produce fertile male and female gametes at an optimal ratio. Haploid malaria parasites lack sex chromosomes, and sex-ratio is an adaptive and changeable trait to optimize transmission success in response to varying conditions, including multiplicity of infection and immune status of the host. The molecular mechanisms of sexual development hold the key to new transmission blocking interventions and to a broader understanding of how life cycle decisions in an important group of parasites can be regulated. Recent breakthroughs have identified a master regulator for commitment to sexual development, but how one transcription factor can give rise to the completely different gene expression programs of male and female gametocytes has remained elusive. Successful reprogramming experiments and genetic screens in a rodent model have now led to the identification of a small panel of genes, mostly encoding putative nucleic acid binding proteins which I propose here will unlock the question of how sex ratio is determined. By applying a combination of targeted biochemical, cell biological and genetic techniques I aim to characterize the function of three strongly supported, male-determining candidate genes. The obtained results will provide insights into the molecular mechanisms facilitating sex, and thus transmission, of malaria parasites. Moreover, this study will elucidate the fascinating biology of sex determination in an ancient and divergent eukaryote lacking sex chromosomes.


Net EU contribution
€ 191 852,16
901 87 Umea

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Norra Sverige Övre Norrland Västerbottens län
Activity type
Higher or Secondary Education Establishments
Other funding
€ 0,00