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Article ; Online: 10 Questions and 4 experts on Corona: Answers by Akiko Iwasaki, Gérard Krause, Samuel Alizon, and Rino Rappuoli.

Carret, Celine K

2020 Volume 12, Issue 5, Page(s) e12317

Abstract: A multi-person interview on the unrolling corona pandemic with Samuel Alizon, Akiko Iwasaki, Gerard Krause and Rino Rappuoli. ...

Abstract	A multi-person interview on the unrolling corona pandemic with Samuel Alizon, Akiko Iwasaki, Gerard Krause and Rino Rappuoli.
MeSH term(s)	Humans ; Pandemics
Keywords	covid19
Language	English
Publishing date	2020-04-24
Publishing country	England
Document type	Interview
ZDB-ID	2467145-9
ISSN	1757-4684 ; 1757-4676
ISSN (online)	1757-4684
ISSN	1757-4676
DOI	10.15252/emmm.202012317
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Article ; Online: 10 Questions and 4 experts on Corona

Celine K Carret

EMBO Molecular Medicine, Vol 12, Iss 5, Pp n/a-n/a (2020)

2020

Keywords	Medicine (General) ; R5-920 ; Genetics ; QH426-470
Language	English
Publishing date	2020-05-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Dietary alterations modulate susceptibility to Plasmodium infection.

Zuzarte-Luís, Vanessa / Mello-Vieira, João / Marreiros, Inês M / Liehl, Peter / Chora, Ângelo F / Carret, Céline K / Carvalho, Tânia / Mota, Maria M

Nature microbiology

2017 Volume 2, Issue 12, Page(s) 1600–1607

Abstract: The relevance of genetic factors in conferring protection to severe malaria has been demonstrated, as in the case of sickle cell trait and G6PD ... ...

Abstract	The relevance of genetic factors in conferring protection to severe malaria has been demonstrated, as in the case of sickle cell trait and G6PD deficiency
MeSH term(s)	Acetylcysteine/metabolism ; Animals ; Antioxidants/metabolism ; Diet, High-Fat/methods ; Disease Models, Animal ; Female ; Gene Expression Profiling ; Glucose Tolerance Test ; Glucosephosphate Dehydrogenase Deficiency/metabolism ; Hep G2 Cells ; Hepatocytes/metabolism ; Hepatocytes/parasitology ; Host-Parasite Interactions/genetics ; Humans ; Liver/metabolism ; Liver/parasitology ; Liver Diseases/metabolism ; Liver Diseases/parasitology ; Macrophages/parasitology ; Macrophages/pathology ; Malaria/blood ; Malaria/diet therapy ; Malaria/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Oxidative Stress ; Parasite Load ; Plasmodium berghei ; Reactive Oxygen Species ; Sickle Cell Trait/metabolism ; Sporozoites/metabolism
Chemical Substances	Antioxidants ; Reactive Oxygen Species ; Acetylcysteine (WYQ7N0BPYC)
Language	English
Publishing date	2017-09-25
Publishing country	England
Document type	Journal Article
ISSN	2058-5276
ISSN (online)	2058-5276
DOI	10.1038/s41564-017-0025-2
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Article ; Online: Genomic variation in two gametocyte non-producing Plasmodium falciparum clonal lines.

Campino, Susana / Benavente, Ernest Diez / Assefa, Samuel / Thompson, Eloise / Drought, Laura G / Taylor, Catherine J / Gorvett, Zaria / Carret, Celine K / Flueck, Christian / Ivens, Al C / Kwiatkowski, Dominic P / Alano, Pietro / Baker, David A / Clark, Taane G

Malaria journal

2016 Volume 15, Page(s) 229

Abstract: Background: Transmission of the malaria parasite Plasmodium falciparum from humans to the mosquito vector requires differentiation of a sub-population of asexual forms replicating within red blood cells into non-dividing male and female gametocytes. The ...

Abstract	Background: Transmission of the malaria parasite Plasmodium falciparum from humans to the mosquito vector requires differentiation of a sub-population of asexual forms replicating within red blood cells into non-dividing male and female gametocytes. The nature of the molecular mechanism underlying this key differentiation event required for malaria transmission is not fully understood. Methods: Whole genome sequencing was used to examine the genomic diversity of the gametocyte non-producing 3D7-derived lines F12 and A4. These lines were used in the recent detection of the PF3D7_1222600 locus (encoding PfAP2-G), which acts as a genetic master switch that triggers gametocyte development. Results: The evolutionary changes from the 3D7 parental strain through its derivatives F12 (culture-passage derived cloned line) and A4 (transgenic cloned line) were identified. The genetic differences including the formation of chimeric var genes are presented. Conclusion: A genomics resource is provided for the further study of gametocytogenesis or other phenotypes using these parasite lines.
MeSH term(s)	Gametogenesis ; Genome, Protozoan ; Plasmodium falciparum/genetics ; Plasmodium falciparum/physiology ; Polymorphism, Genetic ; Sequence Analysis, DNA
Language	English
Publishing date	2016-04-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2091229-8
ISSN	1475-2875 ; 1475-2875
ISSN (online)	1475-2875
ISSN	1475-2875
DOI	10.1186/s12936-016-1254-1
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Article ; Online: Genome-wide RIP-Chip analysis of translational repressor-bound mRNAs in the Plasmodium gametocyte.

Guerreiro, Ana / Deligianni, Elena / Santos, Jorge M / Silva, Patricia A G C / Louis, Christos / Pain, Arnab / Janse, Chris J / Franke-Fayard, Blandine / Carret, Celine K / Siden-Kiamos, Inga / Mair, Gunnar R

Genome biology

2014 Volume 15, Issue 11, Page(s) 493

Abstract: Background: Following fertilization, the early proteomes of metazoans are defined by the translation of stored but repressed transcripts; further embryonic development relies on de novo transcription of the zygotic genome. During sexual development of ... ...

Abstract	Background: Following fertilization, the early proteomes of metazoans are defined by the translation of stored but repressed transcripts; further embryonic development relies on de novo transcription of the zygotic genome. During sexual development of Plasmodium berghei, a rodent model for human malaria species including P. falciparum, the stability of repressed mRNAs requires the translational repressors DOZI and CITH. When these repressors are absent, Plasmodium zygote development and transmission to the mosquito vector is halted, as hundreds of transcripts become destabilized. However, which mRNAs are direct targets of these RNA binding proteins, and thus subject to translational repression, is unknown. Results: We identify the maternal mRNA contribution to post-fertilization development of P. berghei using RNA immunoprecipitation and microarray analysis. We find that 731 mRNAs, approximately 50% of the transcriptome, are associated with DOZI and CITH, allowing zygote development to proceed in the absence of RNA polymerase II transcription. Using GFP-tagging, we validate the repression phenotype of selected genes and identify mRNAs relying on the 5' untranslated region for translational control. Gene deletion reveals a novel protein located in the ookinete crystalloid with an essential function for sporozoite development. Conclusions: Our study details for the first time the P. berghei maternal repressome. This mRNA population provides the developing ookinete with coding potential for key molecules required for life-cycle progression, and that are likely to be critical for the transmission of the malaria parasite from the rodent and the human host to the mosquito vector.
MeSH term(s)	Animals ; Gene Expression Regulation, Developmental ; Germ Cells/growth & development ; Humans ; Malaria, Falciparum/genetics ; Malaria, Falciparum/parasitology ; Malaria, Falciparum/transmission ; Microarray Analysis ; Plasmodium berghei/genetics ; Plasmodium berghei/growth & development ; Plasmodium berghei/pathogenicity ; Plasmodium falciparum/genetics ; Plasmodium falciparum/pathogenicity ; RNA, Messenger/biosynthesis ; RNA, Messenger/genetics ; RNA-Binding Proteins/biosynthesis ; RNA-Binding Proteins/genetics ; Transcriptome ; Zygote/growth & development
Chemical Substances	RNA, Messenger ; RNA-Binding Proteins
Language	English
Publishing date	2014-11-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2040529-7
ISSN	1474-760X ; 1465-6914 ; 1465-6906
ISSN (online)	1474-760X ; 1465-6914
ISSN	1465-6906
DOI	10.1186/s13059-014-0493-0
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Article ; Online: Gene copy number variation throughout the Plasmodium falciparum genome.

Cheeseman, Ian H / Gomez-Escobar, Natalia / Carret, Celine K / Ivens, Alasdair / Stewart, Lindsay B / Tetteh, Kevin K A / Conway, David J

BMC genomics

2009 Volume 10, Page(s) 353

Abstract: Background: Gene copy number variation (CNV) is responsible for several important phenotypes of the malaria parasite Plasmodium falciparum, including drug resistance, loss of infected erythrocyte cytoadherence and alteration of receptor usage for ... ...

Abstract	Background: Gene copy number variation (CNV) is responsible for several important phenotypes of the malaria parasite Plasmodium falciparum, including drug resistance, loss of infected erythrocyte cytoadherence and alteration of receptor usage for erythrocyte invasion. Despite the known effects of CNV, little is known about its extent throughout the genome. Results: We performed a whole-genome survey of CNV genes in P. falciparum using comparative genome hybridisation of a diverse set of 16 laboratory culture-adapted isolates to a custom designed high density Affymetrix GeneChip array. Overall, 186 genes showed hybridisation signals consistent with deletion or amplification in one or more isolate. There is a strong association of CNV with gene length, genomic location, and low orthology to genes in other Plasmodium species. Sub-telomeric regions of all chromosomes are strongly associated with CNV genes independent from members of previously described multigene families. However, approximately 40% of CNV genes were located in more central regions of the chromosomes. Among the previously undescribed CNV genes, several that are of potential phenotypic relevance are identified. Conclusion: CNV represents a major form of genetic variation within the P. falciparum genome; the distribution of gene features indicates the involvement of highly non-random mutational and selective processes. Additional studies should be directed at examining CNV in natural parasite populations to extend conclusions to clinical settings.
MeSH term(s)	Animals ; Comparative Genomic Hybridization ; DNA, Protozoan/genetics ; Gene Deletion ; Gene Dosage ; Genome, Protozoan ; Oligonucleotide Array Sequence Analysis ; Plasmodium falciparum/genetics
Chemical Substances	DNA, Protozoan
Language	English
Publishing date	2009-08-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1471-2164
ISSN (online)	1471-2164
DOI	10.1186/1471-2164-10-353
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Article ; Online: Genome wide adaptations of Plasmodium falciparum in response to lumefantrine selective drug pressure.

Mwai, Leah / Diriye, Abdi / Masseno, Victor / Muriithi, Steven / Feltwell, Theresa / Musyoki, Jennifer / Lemieux, Jacob / Feller, Avi / Mair, Gunnar R / Marsh, Kevin / Newbold, Chris / Nzila, Alexis / Carret, Céline K

PloS one

2012 Volume 7, Issue 2, Page(s) e31623

Abstract: The combination therapy of the Artemisinin-derivative Artemether (ART) with Lumefantrine (LM) (Coartem®) is an important malaria treatment regimen in many endemic countries. Resistance to Artemisinin has already been reported, and it is feared that LM ... ...

Abstract	The combination therapy of the Artemisinin-derivative Artemether (ART) with Lumefantrine (LM) (Coartem®) is an important malaria treatment regimen in many endemic countries. Resistance to Artemisinin has already been reported, and it is feared that LM resistance (LMR) could also evolve quickly. Therefore molecular markers which can be used to track Coartem® efficacy are urgently needed. Often, stable resistance arises from initial, unstable phenotypes that can be identified in vitro. Here we have used the Plasmodium falciparum multidrug resistant reference strain V1S to induce LMR in vitro by culturing the parasite under continuous drug pressure for 16 months. The initial IC(50) (inhibitory concentration that kills 50% of the parasite population) was 24 nM. The resulting resistant strain V1S(LM), obtained after culture for an estimated 166 cycles under LM pressure, grew steadily in 378 nM of LM, corresponding to 15 times the IC(50) of the parental strain. However, after two weeks of culturing V1S(LM) in drug-free medium, the IC(50) returned to that of the initial, parental strain V1S. This transient drug tolerance was associated with major changes in gene expression profiles: using the PFSANGER Affymetrix custom array, we identified 184 differentially expressed genes in V1S(LM). Among those are 18 known and putative transporters including the multidrug resistance gene 1 (pfmdr1), the multidrug resistance associated protein and the V-type H+ pumping pyrophosphatase 2 (pfvp2) as well as genes associated with fatty acid metabolism. In addition we detected a clear selective advantage provided by two genomic loci in parasites grown under LM drug pressure, suggesting that all, or some of those genes contribute to development of LM tolerance--they may prove useful as molecular markers to monitor P. falciparum LM susceptibility.
MeSH term(s)	Animals ; Antimalarials/pharmacology ; Drug Design ; Erythrocytes/drug effects ; Erythrocytes/parasitology ; Ethanolamines/pharmacology ; Fluorenes/pharmacology ; Gene Expression Profiling ; Humans ; Inhibitory Concentration 50 ; Likelihood Functions ; Linear Models ; Lumefantrine ; Malaria/drug therapy ; Mutation ; Oligonucleotide Array Sequence Analysis ; Parasites ; Phenotype ; Plasmodium falciparum/genetics ; Polymerase Chain Reaction/methods ; RNA, Messenger/metabolism
Chemical Substances	Antimalarials ; Ethanolamines ; Fluorenes ; RNA, Messenger ; Lumefantrine (F38R0JR742)
Language	English
Publishing date	2012-02-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0031623
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Article ; Online: Plasmodium translationally repressed gene products are essential for parasite development and malaria transmission

Santos Jorge M / Rao Pavitra N / Guerreiro Ana / Pinho Leonor / Carret Céline K / Franke-Fayard Blandine MD / Templeton Thomas J / Janse Chris J / Mair Gunnar R

Malaria Journal, Vol 11, Iss Suppl 1, p P

2012 Volume 85

Keywords	Arctic medicine. Tropical medicine ; RC955-962 ; Infectious and parasitic diseases ; RC109-216
Language	English
Publishing date	2012-10-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Genome wide adaptations of Plasmodium falciparum in response to lumefantrine selective drug pressure.

Leah Mwai / Abdi Diriye / Victor Masseno / Steven Muriithi / Theresa Feltwell / Jennifer Musyoki / Jacob Lemieux / Avi Feller / Gunnar R Mair / Kevin Marsh / Chris Newbold / Alexis Nzila / Céline K Carret

PLoS ONE, Vol 7, Iss 2, p e

2012 Volume 31623

Abstract	The combination therapy of the Artemisinin-derivative Artemether (ART) with Lumefantrine (LM) (Coartem®) is an important malaria treatment regimen in many endemic countries. Resistance to Artemisinin has already been reported, and it is feared that LM resistance (LMR) could also evolve quickly. Therefore molecular markers which can be used to track Coartem® efficacy are urgently needed. Often, stable resistance arises from initial, unstable phenotypes that can be identified in vitro. Here we have used the Plasmodium falciparum multidrug resistant reference strain V1S to induce LMR in vitro by culturing the parasite under continuous drug pressure for 16 months. The initial IC(50) (inhibitory concentration that kills 50% of the parasite population) was 24 nM. The resulting resistant strain V1S(LM), obtained after culture for an estimated 166 cycles under LM pressure, grew steadily in 378 nM of LM, corresponding to 15 times the IC(50) of the parental strain. However, after two weeks of culturing V1S(LM) in drug-free medium, the IC(50) returned to that of the initial, parental strain V1S. This transient drug tolerance was associated with major changes in gene expression profiles: using the PFSANGER Affymetrix custom array, we identified 184 differentially expressed genes in V1S(LM). Among those are 18 known and putative transporters including the multidrug resistance gene 1 (pfmdr1), the multidrug resistance associated protein and the V-type H+ pumping pyrophosphatase 2 (pfvp2) as well as genes associated with fatty acid metabolism. In addition we detected a clear selective advantage provided by two genomic loci in parasites grown under LM drug pressure, suggesting that all, or some of those genes contribute to development of LM tolerance--they may prove useful as molecular markers to monitor P. falciparum LM susceptibility.
Keywords	Medicine ; R ; Science ; Q
Subject code	572
Language	English
Publishing date	2012-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Gene copy number variation throughout the Plasmodium falciparum genome

Stewart Lindsay B / Ivens Alasdair / Carret Celine K / Gomez-Escobar Natalia / Cheeseman Ian H / Tetteh Kevin KA / Conway David J

BMC Genomics, Vol 10, Iss 1, p

2009 Volume 353

Abstract: Abstract Background Gene copy number variation (CNV) is responsible for several important phenotypes of the malaria parasite Plasmodium falciparum , including drug resistance, loss of infected erythrocyte cytoadherence and alteration of receptor usage ... ...

Abstract	Abstract Background Gene copy number variation (CNV) is responsible for several important phenotypes of the malaria parasite Plasmodium falciparum , including drug resistance, loss of infected erythrocyte cytoadherence and alteration of receptor usage for erythrocyte invasion. Despite the known effects of CNV, little is known about its extent throughout the genome. Results We performed a whole-genome survey of CNV genes in P. falciparum using comparative genome hybridisation of a diverse set of 16 laboratory culture-adapted isolates to a custom designed high density Affymetrix GeneChip array. Overall, 186 genes showed hybridisation signals consistent with deletion or amplification in one or more isolate. There is a strong association of CNV with gene length, genomic location, and low orthology to genes in other Plasmodium species. Sub-telomeric regions of all chromosomes are strongly associated with CNV genes independent from members of previously described multigene families. However, ~40% of CNV genes were located in more central regions of the chromosomes. Among the previously undescribed CNV genes, several that are of potential phenotypic relevance are identified. Conclusion CNV represents a major form of genetic variation within the P. falciparum genome; the distribution of gene features indicates the involvement of highly non-random mutational and selective processes. Additional studies should be directed at examining CNV in natural parasite populations to extend conclusions to clinical settings.
Keywords	Genetics ; QH426-470 ; Biology (General) ; QH301-705.5 ; Science ; Q ; DOAJ:Genetics ; DOAJ:Biology ; DOAJ:Biology and Life Sciences ; Biotechnology ; TP248.13-248.65
Subject code	572
Language	English
Publishing date	2009-08-01T00:00:00Z
Publisher	BioMed Central
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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