1. A toolbox for conditional control of gene expression in apicomplexan parasites
- Author
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Olivier Silvie, Sylvie Briquet, Mathieu Gissot, Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), MG is supported by grants from the Pasteur Institute International Network and the Region Hauts-de-France. OS is supported by the Laboratoire d'Excellence ParaFrap (ANR-11-LABX-0024), the Agence Nationale de la Recherche (ANR-16-CE15-0010 and ANR-20-CE18-0013), and the Fondation pour la Recherche Médicale (EQU201903007823)., ANR-11-LABX-0024,ParaFrap,Alliance française contre les maladies parasitaires(2011), ANR-16-CE15-0010,JUNCTIONPARTNERS,Caractérisation des partenaires de la cellule hôte impliqués dans la formation de la jonction mobile chez les Apicomplexes(2016), ANR-20-CE18-0013,MALPROP,Cibler une protéine de Plasmodium à domaine propeller pour prévenir l'infection du foie au cours du paludisme(2020), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Gissot, Mathieu, Laboratoires d'excellence - Alliance française contre les maladies parasitaires - - ParaFrap2011 - ANR-11-LABX-0024 - LABX - VALID, Caractérisation des partenaires de la cellule hôte impliqués dans la formation de la jonction mobile chez les Apicomplexes - - JUNCTIONPARTNERS2016 - ANR-16-CE15-0010 - AAPG2016 - VALID, and Cibler une protéine de Plasmodium à domaine propeller pour prévenir l'infection du foie au cours du paludisme - - MALPROP2020 - ANR-20-CE18-0013 - AAPG2020 - VALID
- Subjects
Plasmodium ,Mutant ,Gene Expression ,Computational biology ,Biology ,Microbiology ,DNA sequencing ,03 medical and health sciences ,0302 clinical medicine ,Genome editing ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,parasitic diseases ,Gene expression ,Recombinase ,Animals ,[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology ,Parasites ,Molecular Biology ,Gene ,030304 developmental biology ,0303 health sciences ,Gene knockdown ,Genes, Essential ,Promoter ,3. Good health ,[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,Toxoplasma ,[SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology ,030217 neurology & neurosurgery - Abstract
International audience; Apicomplexan parasites encompass diverse pathogens for humans and animals, including the causative agents of malaria and toxoplasmosis, Plasmodium spp. and Toxoplasma gondii. Genetic manipulation of these parasites has become central to explore parasite biology, unravel gene function and identify new targets for therapeutic strategies. Tremendous progress has been achieved over the past years with the advent of next generation sequencing and powerful genome editing methods. In particular, various methods for conditional gene expression have been developed in both Plasmodium and Toxoplasma to knockout or knockdown essential genes, or for inducible expression of master developmental regulators or mutant versions of proteins. Conditional gene expression can be achieved at three distinct levels. At the DNA level, inducible site-specific recombinases allow conditional genome editing. At the RNA level, regulation can be achieved during transcription, using stage-specific or regulatable promoters, or post-transcriptionally through alteration of mRNA stability or translation. At the protein level, several systems have been developed for inducible degradation or displacement of a protein of interest. In this review, we provide an overview of current systems for conditional control of gene expression in Plasmodium and Toxoplasma parasites, highlighting the advantages and limitations of each approach.
- Published
- 2021