Project description DEENESFRITPL 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. Show the project objective Hide the project objective Objective 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. Fields of science medical and health scienceshealth sciencesinfectious diseasesmalarianatural sciencesbiological sciencesbiochemistrybiomoleculesnucleic acidsnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesgeneticschromosomesnatural sciencesbiological scienceszoologyinvertebrate zoology Keywords Sex determination Plasmodium Gametocytogenesis Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2019 - Individual Fellowships Call for proposal H2020-MSCA-IF-2019 See other projects for this call Funding Scheme MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinator UMEA UNIVERSITET Net EU contribution € 191 852,16 Address Universitetomradet 901 87 Umea Sweden See on map Region Norra Sverige Övre Norrland Västerbottens län Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
