Last Updated: 07/10/2025
A genome on the move: gene regulatory networks and epigenetics of the malaria parasite in the mosquito
Objectives
The objective of this project is to determine how chromatin structure and epigenetics control development and transcriptional variation in P. falciparum, and how alterations in this non-coding part of the parasite genome can contribute to the eradication of malaria, with a pioneering approach based on the mosquito biological model and combining epigenomics, the study of 3D chromatin conformation and CRISPR-based regulatory element editing.
Human malaria is a devastating disease and one of the leading causes of poverty in developing countries. Throughout their life cycle, malaria parasites move between different hosts (humans and mosquitoes), organs, and tissues, where they are subjected to heterogeneous environments and strong selective pressures. In order to multiply, survive, and transmit, the parasite has developed mechanisms to rapidly vary its phenotype throughout development and in response to specific stimuli within the host. Changes in chromatin structure play a critical role in regulating transcriptional variation in Plasmodium falciparum; however, the mechanisms and regulatory elements involved are poorly understood. The developmental stages of the parasite in the mosquito are of enormous interest for investigating how phenotypic variability is generated during cell differentiation and adaptation to new conditions in the host in vivo. To fill this gap, this project builds on previous research from our group showing that mosquito passage affects the expression of malaria parasite virulence genes, and that transcription factors and long non-coding RNAs appear to play crucial roles in regulating variant clonal expression.
Jun 2020 — May 2023
$370,145
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