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Last Updated: 27/02/2023
Defining the functional role of a novel Plasmodium falciparum protein domain involved in liquid-liquid phase separation
Objectives
To uncover the functional role for a unique, previously uncharacterized P. falciparum protein domain.
Specific objectives:
- To characterize this domain by studying LLPS in vivo using a fluorescent reporter assay and directly in P. falciparum parasites.
- To determine in vitro protein interaction partners via protein pulldown assays and mass spectrometry leading to creation of transgenic parasites.
- To study the in vivo effect of modifications to this domain using CRISPR/Cas9.
Principal Institution
Principal Investigators / Focal Persons
Rationale and Abstract
Malaria constitutes an enormous global health burden, and there is an urgent need to identify new targets for antimalarial therapy to eradicate this parasitic disease. In the malaria parasite, P. falciparum, transcriptional regulation is fundamental to parasite development. Apicomplexan Apetala 2 (ApiAP2) proteins are the main group of transcription factors regulating the malaria parasite lifecycle, acting as developmental switches between parasite life stages. Nine ApiAP2 proteins contain a highly conserved Apicomplexan-specific domain of unknown function, the ACDC domain. We have found that this novel domain may act in oligomerization to drive the formation of cellular liquid condensates by Liquid-Liquid phase separation (LLPS). These studies will provide the first mechanistic explanation for LLPS in malaria parasites.
External reference
Thematic Categories
Date
Jan 2021 — Dec 2023
Total Project Funding
$346,000
Funding Details
Swedish Research Council (SRC), Sweden
Grant number: 2020-06500_VR
SEK 3.15 Million
Project Site
Related Resources
