A5008842145- Research on Leishmaniasis Studies
- Trypanosoma species research and implications
- CRISPR and Genetic Engineering
- Chromosomal and Genetic Variations
- Malaria Research and Control
- Evolution and Genetic Dynamics
- Innovation and Socioeconomic Development
- DNA Repair Mechanisms
- Nuclear Structure and Function
- Biochemical and Molecular Research
- Lysosomal Storage Disorders Research
- HIV/AIDS drug development and treatment
- Renal Diseases and Glomerulopathies
- HIV Research and Treatment
Institut de Recherche pour le Développement
2017-2021
Centre National de la Recherche Scientifique
2017-2021
Université de Montpellier
2013-2021
Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes
2021
Maladies Infectieuses et Vecteurs: Écologie, Génétique, Évolution et Contrôle
2020
Centre Hospitalier Universitaire de Montpellier
2017
Protozoan pathogens that cause leishmaniasis in humans are relatively refractory to genetic manipulation. In this work, we implemented the CRISPR-Cas9 system Leishmania parasites and demonstrated its efficient use for genome editing. The Cas9 endonuclease was expressed under control of Dihydrofolate Reductase-Thymidylate Synthase (DHFR-TS) promoter single guide RNA produced U6snRNA terminator. As a proof concept, chose knockout tandemly repeated gene family, paraflagellar rod-2 locus. We...
Leishmania, a unicellular eukaryotic parasite, is unique model for aneuploidy and cellular heterogeneity, along with their potential role in adaptation to environmental stresses. Somy variation within clonal populations was previously explored small subset of chromosomes using fluorescence hybridization methods. This phenomenon, termed mosaic (MA), might have important evolutionary functional implications but remains under-explored due technological limitations. Here, we applied validated...
Leishmania and Trypanosoma are unicellular parasites that possess markedly original biological features as compared to other eukaryotes. The genome displays a constitutive 'mosaic aneuploidy', whereas in brucei, the megabase-sized chromosomes diploid. We accurately analysed DNA replication parameters three species brucei well mouse embryonic fibroblasts (MEF). Active origins were visualized at single molecule level using molecular combing. More than one active origin was found on most...
The malaria parasite Plasmodium falciparum has evolved an unusual genome structure. majority of the is relatively stable, with mutation rates similar to most eukaryotic species. However, some regions are very unstable high recombination rates, driving generation new immune evasion-associated var genes. molecular factors controlling inconsistent stability this not known. Here we studied roles two putative RecQ helicases in P. falciparum, PfBLM and PfWRN. When PfWRN was knocked down, increased...
Parasites of the Leishmania donovani complex are responsible for visceral leishmaniasis, a vector-borne disease transmitted through bite female phlebotomine sand flies. As well as human hosts, these parasites infect many mammals which can serve reservoirs. Dogs particularly important reservoirs in Europe. Transmission is widespread across Asia, Africa, Americas, and Mediterranean basin, including South France. Visceral leishmaniasis poses fatal threat if left untreated. Research into...
The mechanics of DNA replication and cell cycling are well-characterized in model organisms, but less is known about these basic aspects biology early-diverging Apicomplexan parasites, which do not divide by canonical binary fission undergo unconventional cycles. Schizogony the malaria parasite, Plasmodium, generates ~16-24 new nuclei via independent, asynchronous rounds genome prior to cytokinesis little control that facilitates this. We have characterised dynamics P. falciparum throughout...
Nucleoporins are evolutionary conserved proteins mainly involved in the constitution of nuclear pores and trafficking between nucleus cytoplasm, but also increasingly viewed as main actors chromatin dynamics intra-nuclear mitotic events. Here, we determined cellular localization nucleoporin Mlp2 'divergent' eukaryotes Leishmania major Trypanosoma brucei. In both protozoa, displayed an atypical for a nucleoporin, essentially intranuclear, preferentially periphery nucleolus during interphase;...
Trypanosomatids are divergent eukaryotes of high medical and economical relevance. Their biology exhibits original features that remain poorly understood; particularly, Leishmania is known for its degree genomic plasticity makes manipulation challenging. CRISPR-Cas9 has been applied successfully to these parasites providing a robust tool study non-essential gene functions. Here, we have developed versatile inducible system combining Di-Cre recombinase advantages. Cas9 used integrate the LoxP...
Leishmania parasites possess a unique and complex cytoskeletal structure termed flagellum attachment zone (FAZ) connecting the base of to one side flagellar pocket (FP), an invagination cell body membrane sole site for endocytosis exocytosis. This is involved in FP architecture morphogenesis, but its precise role molecular composition remain enigmatic. Here, we characterized FAZ7, only known FAZ protein containing kinesin motor domain, part clade trypanosomatid-specific kinesins with unknown...
Abstract Maintenance of stable ploidy over continuous mitotic events is a paradigm for most higher eukaryotes. Defects in chromosome segregation and/or replication can lead to aneuploidy, condition often considered deleterious. However, Leishmania , Protozoan parasite, aneuploidy constitutive feature, where variations somies represent mechanism gene expression adaptation, possibly impacting phenotypes. Strikingly, clonal populations display cell-to-cell somy variation, phenomenon named...
Abstract Leishmania , a unicellular eukaryotic parasite, is unique model for aneuploidy and cellular heterogeneity, along with their potential role in adaptation to environmental stresses. Somy variation within clonal populations was previously explored small subset of chromosomes using fluorescence hybridization methods. This phenomenon, termed mosaic (MA), might have important evolutionary functional implications but remains under-explored due technological limitations. Here, we applied...