The Organization and Function of the Toxoplasma Daughter Cell Scaffold

NIH RePORTER · NIH · R01 · $505,519 · view on reporter.nih.gov ↗

Abstract

Uncontrolled Toxoplasma growth is the primary mechanism by which the parasite causes severe and life-threatening disease. The parasite replicates by a process termed endodyogeny, where two daughter parasites form within a single mother. A key step in endodyogeny is formation of the daughter cell inner membrane complex, which is an unique organelle that lies directly underneath the plasma membrane and is required for parasite motility and replication. During daughter cell development, the nascent IMC emerges from a complex named the daughter cell scaffold (DCS). Despite its importance, the DCS is poorly characterized and few of its constituent proteins are known. Here, we hypothesize that the Toxoplasma F-box protein, TgFBXO1, is a critical component of the DCS. To test our hypothesis, we will determine: i) how TgFBXO1 is targeted to the DCS, ii) how TgFBXO1 regulates inner membrane complex development and organization, and iii) which TgFBXO1-interacting proteins are important for inner membrane complex development. Together, these studies will provide in depth mechanistic detail for a protein complex that is critical for growth of an important protozoan pathogen. Furthermore, they were serve as a springboard for future studies aimed at developing novel anti-parasitic drugs that function by targeting this complex.

Key facts

NIH application ID
11244248
Project number
7R01AI150240-06
Recipient
VIRGINIA POLYTECHNIC INST AND ST UNIV
Principal Investigator
Ira J Blader
Activity code
R01
Funding institute
NIH
Fiscal year
2024
Award amount
$505,519
Award type
7
Project period
2020-01-08 → 2026-12-31