Last Updated: 07/10/2025
Epigenetics of adaptation in the malaria parasite Plasmodium falciparum
Objectives
The objective of this project is to unravel the epigenetic basis of parasite plasticity and develop new tools and model systems to study and block adaptation in the malaria parasite.
The specific objectives are:
- regulatory plasticity in the parasite will be assessed throughout different stages of the mosquito life cycle using single-cell transcriptomics and epigenomics;
- the regulators involved in parasite adaptation and survival in the mosquito will be functionally validated using a novel temperature-dependent CRISPR-CAS gene editing tool; and
- to develop an ex vivo mosquito midgut culture model using a cell-tracking system that will improve tissue viability and support malaria infections.
Plasmodium’s ability to rapidly and reversibly change phenotypes is seriously compromising the effectiveness of malaria control strategies and is of utmost importance in the context of climate change and globalization. Understanding the mechanisms of rapid adaptation can block transmission, but our understanding is currently insufficient. Furthermore, progress in malaria research is hampered by a lack of appropriate experimental systems that recreate the natural transmission environment, as well as new tools to defeat this deadly pathogen. The project is highly inter- and multidisciplinary. It integrates knowledge from multiple fields, including parasitology, genomics, molecular and cell biology, and developmental biology. It also combines expertise in areas such as epigenetics, malaria transmission, single-cell multi-omic analysis, gene editing, mosquito transgenesis, and intestinal homeostasis in insects. Taken together, the project is poised to expand the boundaries of our current understanding of rapid pathogen adaptation mechanisms and bring us closer to finding new, more effective tools and strategies to control and eradicate malaria.
Jan 2023
$378,696
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