Evidence map›Paper›PMID 30726238›Full record

ArticlePLoS biology2019

A mutagenesis screen for essential plastid biogenesis genes in human malaria parasites.

Yong Tang, Thomas R Meister, Marta Walczak, Michael J Pulkoski-Gross, Sanjay B Hari, Robert T Sauer, Katherine Amberg-Johnson, Ellen Yeh

Abstract read
In one paragraph

Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed.

  1. Article
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  7. Antimalarial drug discovery: progress and approaches.Nature reviews. Drug discovery · 2023
    Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Review
  15. Article
  16. GeneTargeter: AutomatedThe CRISPR journal · 2022
    Article
  17. Article
  18. Article
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Yong TangDepartment of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of America.ORCID 0000-0002-9269-9765
Thomas R MeisterDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California, United States of America.ORCID 0000-0001-9743-8110
Marta WalczakDepartment of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of America.ORCID 0000-0003-2317-6650
Michael J Pulkoski-GrossDepartment of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of America.
Sanjay B HariDepartment of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.ORCID 0000-0003-0606-9896
Robert T SauerDepartment of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
Katherine Amberg-JohnsonDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, United States of America.ORCID 0000-0003-2707-2912
Ellen YehDepartment of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of America.

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007365 · NIGMS · STANFORD UNIVERSITY · PI CHUA, KATRIN F · 1985 to 2021
$33.8M
Supplement to Enhance Wellness and Resiliency in the Graduate EnvironmentT32GM007276 · NIGMS · STANFORD UNIVERSITY · PI MORRISON, ASHBY J. · 1985 to 2023
$32.9M
REPRESSOR &ANTIREPRESSOR PROTEINS OF BACTERIOPHAGER01AI016892 · NIAID · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BAKER, TANIA A, SAUER, ROBERT T · 1985 to 2022
$13.0M
Harnessing the Unique Biogenesis of the Apicomplexan plastid organelle forAntimalarial TargetsR01AI141366 · NIAID · STANFORD UNIVERSITY · PI YEH, ELLEN · 2019 to 2023
$2.9M
Defining the novel eukaryotic biology of the Apicomplexan plastidDP5OD012119 · OD · STANFORD UNIVERSITY · PI YEH, ELLEN · 2012 to 2016
$2.0M
Deciphering apicoplast function during blood stage Plasmodium infectionK08AI097239 · NIAID · STANFORD UNIVERSITY · PI YEH, ELLEN · 2012 to 2016
$666k
High Throughput DNA Sequencer UpgradeS10OD018220 · OD · STANFORD UNIVERSITY · PI COLLER, JOHN · 2014 to 2014
$596k
Quality Control of Membrane ProteinsF32GM116241 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI HARI, SANJAY B · 2015 to 2016
$112k
NIAID NIH HHS K08 AI097239NIAID NIH HHS R01 AI016892NIAID NIH HHS R01 AI141366NIGMS NIH HHS F32 GM116241NIGMS NIH HHS T32 GM007276NIGMS NIH HHS T32 GM007365NIH HHS DP5 OD012119NIH HHS S10 OD018220Wellcome Trust
6 · The paper itself

Abstract

Endosymbiosis has driven major molecular and cellular innovations. Plasmodium spp. parasites that cause malaria contain an essential, non-photosynthetic plastid-the apicoplast-which originated from a secondary (eukaryote-eukaryote) endosymbiosis. To discover organellar pathways with evolutionary and biomedical significance, we performed a mutagenesis screen for essential genes required for apicoplast biogenesis in Plasmodium falciparum. Apicoplast(-) mutants were isolated using a chemical rescue that permits conditional disruption of the apicoplast and a new fluorescent reporter for organelle loss. Five candidate genes were validated (out of 12 identified), including a triosephosphate isomerase (TIM)-barrel protein that likely derived from a core metabolic enzyme but evolved a new activity. Our results demonstrate, to our knowledge, the first forward genetic screen to assign essential cellular functions to unannotated P. falciparum genes. A putative TIM-barrel enzyme and other newly identified apicoplast biogenesis proteins open opportunities to discover new mechanisms of organelle biogenesis, molecular evolution underlying eukaryotic diversity, and drug targets against multiple parasitic diseases.

Indexed as

Genes, EssentialMutationApicoplastsCRISPR-Cas SystemsErythrocytesGene OntologyGenes, ReporterGreen Fluorescent ProteinsHumansLuminescent ProteinsMetalloproteasesMolecular Sequence AnnotationMutagenesisOrganelle BiogenesisPlasmodium falciparumProtozoan ProteinsGreen Fluorescent ProteinsLuminescent ProteinsMetalloproteasesProtozoan ProteinsRed Fluorescent ProteinTriose-Phosphate Isomerase

Identifiers

PMID30726238
PMCPMC6380595

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.