Last Updated: 01/12/2025
LAP function in apicomplexan parasite development
Objectives
The objectives of this project are to:
- Test the functional requirement of crystalloids in parasite development. Using chemical disruption of crystalloid assembly we will assess whether the LAPs function downstream of crystalloid formation;
- Define the LAP ‘interactome’ by isolating LAP complexes and determine their protein composition by high-accuracy mass spectrometry (MS);
- Define the crystalloid proteome by determining and comparing the proteomes of crystalloid-positive vs. crystalloid-negative ookinetes to identify other crystalloid components; and
- Investigate the subcellular localization, function and mode of action of new proteins identified from objectives 2 and 3.
London School of Hygiene and Tropical Medicine (LSHTM), United Kingdom
Apicomplexan parasites are widespread protozoan parasites and include major pathogens of humans, domestic animals and livestock. Many existing measures against these parasites remain insufficient for disease control, and new strategies for prophylaxis, treatment and control of transmission are urgently needed. This research proposal focuses on an Apicomplexa-specific conserved family of modular proteins (named LAPs) containing domains implicated in lipid, carbohydrate and protein interaction. In Plasmodium, the LAP family has six conserved members that form a protein complex, localize to distinctive multivesicular organelles named crystalloids, and have essential roles in crystalloid biogenesis and sporozoite development. The uniqueness, complex architectures and conservation of the LAPs strongly point to a conserved function in all apicomplexan parasites, but thus far it is unknown what that function is. Determining the function and mode of action of the LAPs is of much interest both from a parasite cell biological perspective, and as potential molecular targets for antiparasitic chemotherapy.
Jan 2015 — Dec 2018
$561,547
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