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CRISPR/Cas9 and genetic screens in malaria parasites : small genomes, big impact

Title: CRISPR/Cas9 and genetic screens in malaria parasites : small genomes, big impact
Authors: Ishizaki, Takahiro; Hernandez, Sophia; Paoletta, Martina S.; Sanderson, Theo; Bushell, Ellen
Publisher Information: Umeå universitet, Institutionen för molekylärbiologi (Medicinska fakulteten); Umeå universitet, Molekylär Infektionsmedicin, Sverige (MIMS); Instituto de Agrobiotecnología y Biología Molecular (IABIMO), Argentina; Francis Crick Institute London, United Kingdom
Publication Year: 2022
Collection: Umeå University: Publications (DiVA)
Subject Terms: Plasmodium falciparum; biochemical techniques and resources; CRISPR; genetics; malaria; Cell and Molecular Biology; Cell- och molekylärbiologi; Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology); Molecular Biology; Microbiology; Biochemistry or Biopharmacy); Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi); molekylärbiologi; mikrobiologi; biokemi eller biofarmaci)
Description: The ∼30 Mb genomes of the Plasmodium parasites that cause malaria each encode ∼5000 genes, but the functions of the majority remain unknown. This is due to a paucity of functional annotation from sequence homology, which is compounded by low genetic tractability compared with many model organisms. In recent years technical breakthroughs have made forward and reverse genome-scale screens in Plasmodium possible. Furthermore, the adaptation of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-Associated protein 9 (CRISPR/Cas9) technology has dramatically improved gene editing efficiency at the single gene level. Here, we review the arrival of genetic screens in malaria parasites to analyse parasite gene function at a genome-scale and their impact on understanding parasite biology. CRISPR/Cas9 screens, which have revolutionised human and model organism research, have not yet been implemented in malaria parasites due to the need for more complex CRISPR/Cas9 gene targeting vector libraries. We therefore introduce the reader to CRISPR-based screens in the related apicomplexan Toxoplasma gondii and discuss how these approaches could be adapted to develop CRISPR/Cas9 based genome-scale genetic screens in malaria parasites. Moreover, since more than half of Plasmodium genes are required for normal asexual blood-stage reproduction, and cannot be targeted using knockout methods, we discuss how CRISPR/Cas9 could be used to scale up conditional gene knockdown approaches to systematically assign function to essential genes.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
Relation: Biochemical Society Transactions, 0300-5127, 2022, 50:3, s. 1069-1079; PMID 35621119; ISI:000804375700001
DOI: 10.1042/BST20210281
Availability: http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-197999; https://doi.org/10.1042/BST20210281
Rights: info:eu-repo/semantics/openAccess
Accession Number: edsbas.92946B1
Database: BASE