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Last Updated: 24/05/2024

Mechanistic study of Plasmodium apicoplast replication

Objectives

To develop a thorough understanding of Plasmodium apicoplast replication mechanism with particular emphasis on understanding how the different apicoplast replication proteins interact with each other to ensure faithful replication inside the hostile environment of the human host.

Specific objectives:

  1. To delineate the workings of the sole apicoplast DNA polymerase, apPol, and identify the kinetic and structural determinants of fidelity for this enzyme.
  2. To investigate the mechanism of apicoplast replication initiation by delineating the interplay between apicoplast helicase,primase and apPol.
Principal Investigators / Focal Persons

Indrajit Lahiri

Rationale and Abstract

Rapid rise in drug resistant Plasmodium strains is a major public health concern and identifying novel anti-Plasmodium drug targets is a priority. Plasmodium contains an essential organelle called the apicoplast. Apicoplast harbors its own genome, replication of which is essential for pathogen survival. Apiocplast replication is carried out by the apicoplast replisome, components of which are divergent from the human counterparts. This makes apicoplast replication proteins potential drug targets. However, our limited understanding of apicoplast replication is a serious hindrance in developing the apiocplast replisome into a viable drug target. This project will help generate a detailed understanding of how the apicoplast replication proteins function and cross-talk.

Date

Jan 2021 — Dec 2025

Total Project Funding

$474,000

Funding Details
DBT/Wellcome Trust India Alliance, India

Grant ID: IA/I/20/1/504905
INR 35.1 million
Project Site

India

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