Host immune and metabolic determinants of sexual conversion in Plasmodium parasites

Project Details

Description

Understanding the sexual conversion of the malaria parasite is essential to interrupt malaria transmission. At each replicating cycle within erythrocytes, a proportion of asexual parasites converts into non-replicative sexual stages, which are the only forms able to infect mosquitos. The rate at which sexual stages are produced, is known as basal sexual conversion rate. Changes in the host immune and metabolic environment associated with the development of malaria disease, such as depletion of lysophosphatidylcholine in plasma, have been associated with increased sexual conversion rates in vitro.
We hypothesise that immune and metabolite factors that are altered during malaria infection induce sexual conversion in Plasmodium falciparum parasites. In this project, we will develop a new tool that based on expression analysis of sexual stage biomarkers will estimate sexual conversion rates in natural infections. We aim to identify immune factors and metabolites that induce sexual conversion using in-house developed sexual conversion assays, and experimental mosquito infections. Finally, we will explore transcriptional mechanisms driving parasite sexual conversion in the host environment during disease using single cell RNA-sequencing approaches. This research will provide essential knowledge on the factors that affect sexual conversion in the host and potentially inform novel strategies to interrupt transmission.

Description

Understanding the sexual conversion of the malaria parasite is essential to interrupt malaria transmission. At each replicating cycle within erythrocytes, a proportion of asexual parasites converts into non-replicative sexual stages, which are the only forms able to infect mosquitos. The rate at which sexual stages are produced, is known as basal sexual conversion rate. Changes in the host immune and metabolic environment associated with the development of malaria disease, such as depletion of lysophosphatidylcholine in plasma, have been associated with increased sexual conversion rates in vitro.
We hypothesise that immune and metabolite factors that are altered during malaria infection induce sexual conversion in Plasmodium falciparum parasites. In this project, we will develop a new tool that based on expression analysis of sexual stage biomarkers will estimate sexual conversion rates in natural infections. We aim to identify immune factors and metabolites that induce sexual conversion using in-house developed sexual conversion assays, and experimental mosquito infections. Finally, we will explore transcriptional mechanisms driving parasite sexual conversion in the host environment during disease using single cell RNA-sequencing approaches. This research will provide essential knowledge on the factors that affect sexual conversion in the host and potentially inform novel strategies to interrupt transmission.
AcronymIMMETASEX
StatusActive
Effective start/end date1/01/2331/12/26

Funding

  • Research Fund - Flanders: €564,091.20

Flemish disciplinelist

  • Infectious diseases
  • Parasitology
  • Tropical medicine