A genetic screen for attenuated growth identifies genes crucial for intraerythrocytic development of Plasmodium falciparum.

A majority of the Plasmodium falciparum genome codes for genes with unknown functions, which presents a major challenge to understanding the parasite's biology. Large-scale functional analysis of the parasite genome is essential to pave the way for novel therapeutic intervention strategies agai...

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Main Authors: Bharath Balu, Naresh Singh, Steven P Maher, John H Adams
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2010-10-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0013282&type=printable
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author Bharath Balu
Naresh Singh
Steven P Maher
John H Adams
author_facet Bharath Balu
Naresh Singh
Steven P Maher
John H Adams
author_sort Bharath Balu
collection DOAJ
description A majority of the Plasmodium falciparum genome codes for genes with unknown functions, which presents a major challenge to understanding the parasite's biology. Large-scale functional analysis of the parasite genome is essential to pave the way for novel therapeutic intervention strategies against the disease and yet difficulties in genetic manipulation of this deadly human malaria parasite have been a major hindrance for functional analysis of its genome. Here, we used a forward functional genomic approach to study P. falciparum and identify genes important for optimal parasite development in the disease-causing, intraerythrocytic stages. We analyzed 123 piggyBac insertion mutants of P. falciparum for proliferation efficiency in the intraerythrocytic stages, in vitro. Almost 50% of the analyzed mutants showed significant reduction in proliferation efficiency, with 20% displaying severe defects. Functional categorization of genes in the severely attenuated mutants revealed significant enrichment for RNA binding proteins, suggesting the significance of post-transcriptional gene regulation in parasite development and emphasizing its importance as an antimalarial target. This study demonstrates the feasibility of much needed forward genetics approaches for P. falciparum to better characterize its genome and accelerate drug and vaccine development.
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spelling doaj-art-80c66d42375644a4bc620ea4a0d8d0822025-08-20T03:19:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-10-01510e1328210.1371/journal.pone.0013282A genetic screen for attenuated growth identifies genes crucial for intraerythrocytic development of Plasmodium falciparum.Bharath BaluNaresh SinghSteven P MaherJohn H AdamsA majority of the Plasmodium falciparum genome codes for genes with unknown functions, which presents a major challenge to understanding the parasite's biology. Large-scale functional analysis of the parasite genome is essential to pave the way for novel therapeutic intervention strategies against the disease and yet difficulties in genetic manipulation of this deadly human malaria parasite have been a major hindrance for functional analysis of its genome. Here, we used a forward functional genomic approach to study P. falciparum and identify genes important for optimal parasite development in the disease-causing, intraerythrocytic stages. We analyzed 123 piggyBac insertion mutants of P. falciparum for proliferation efficiency in the intraerythrocytic stages, in vitro. Almost 50% of the analyzed mutants showed significant reduction in proliferation efficiency, with 20% displaying severe defects. Functional categorization of genes in the severely attenuated mutants revealed significant enrichment for RNA binding proteins, suggesting the significance of post-transcriptional gene regulation in parasite development and emphasizing its importance as an antimalarial target. This study demonstrates the feasibility of much needed forward genetics approaches for P. falciparum to better characterize its genome and accelerate drug and vaccine development.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0013282&type=printable
spellingShingle Bharath Balu
Naresh Singh
Steven P Maher
John H Adams
A genetic screen for attenuated growth identifies genes crucial for intraerythrocytic development of Plasmodium falciparum.
PLoS ONE
title A genetic screen for attenuated growth identifies genes crucial for intraerythrocytic development of Plasmodium falciparum.
title_full A genetic screen for attenuated growth identifies genes crucial for intraerythrocytic development of Plasmodium falciparum.
title_fullStr A genetic screen for attenuated growth identifies genes crucial for intraerythrocytic development of Plasmodium falciparum.
title_full_unstemmed A genetic screen for attenuated growth identifies genes crucial for intraerythrocytic development of Plasmodium falciparum.
title_short A genetic screen for attenuated growth identifies genes crucial for intraerythrocytic development of Plasmodium falciparum.
title_sort genetic screen for attenuated growth identifies genes crucial for intraerythrocytic development of plasmodium falciparum
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0013282&type=printable
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