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The molecular mechanisms of sex determination in a malaria parasite

Description du projet

La reproduction sexuée du parasite responsable du paludisme

La reproduction sexuée du moustique est nécessaire pour que le parasite Plasmodium, agent responsable du paludisme, se transmette à un nouvel hôte. Des preuves récentes indiquent que le développement sexuel implique un groupe réduit de gènes qui régulent le rapport des sexes, un trait adaptatif primordial pour réussir la transmission en réponse à différentes conditions. Le projet MalariaSex, financé par l’UE, étudiera la fonction de ces gènes et leurs mécanismes sous-jacents. L’identification des mécanismes moléculaires à l’origine du développement sexuel de Plasmodium fera la lumière sur la régulation des décisions concernant le cycle de vie et permettra la conception d’interventions bloquant la transmission.

Objectif

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.

Coordinateur

UMEA UNIVERSITET
Contribution nette de l'UE
€ 191 852,16
Adresse
UNIVERSITETOMRADET
901 87 Umea
Suède

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Région
Norra Sverige Övre Norrland Västerbottens län
Type d’activité
Higher or Secondary Education Establishments
Liens
Coût total
€ 191 852,16