A5091177557- Malaria Research and Control
- Microtubule and mitosis dynamics
- Trypanosoma species research and implications
- Invertebrate Immune Response Mechanisms
- Toxoplasma gondii Research Studies
- Mosquito-borne diseases and control
- Neonatal and Maternal Infections
- Glycosylation and Glycoproteins Research
- Streptococcal Infections and Treatments
- HIV Research and Treatment
- Complement system in diseases
- Multiple Myeloma Research and Treatments
- CRISPR and Genetic Engineering
- Cellular transport and secretion
- Bacteriophages and microbial interactions
- Drug Transport and Resistance Mechanisms
- Ubiquitin and proteasome pathways
- Genomics and Phylogenetic Studies
- Herpesvirus Infections and Treatments
- Sperm and Testicular Function
- Insect Resistance and Genetics
- Chromosomal and Genetic Variations
- Cytomegalovirus and herpesvirus research
- Phosphodiesterase function and regulation
- Advanced biosensing and bioanalysis techniques
University of Geneva
2016-2024
Merck & Co., Inc., Rahway, NJ, USA (United States)
2019
University of Kassel
2019
Swiss National Science Foundation
2019
Cyclerion (United States)
2019
London School of Hygiene & Tropical Medicine
2019
Wellcome Sanger Institute
2011-2017
Centre National de la Recherche Scientifique
2006-2016
Université de Montpellier
2015-2016
Centre National pour la Recherche Scientifique et Technique (CNRST)
2008
Chemical genetics and a global comparative analysis of phosphorylation phospholipids in vivo shows that PKG is the upstream regulator induces calcium signals enables Plasmodium to progress through its complex life cycle.
Malaria is caused by unicellular Plasmodium parasites. relies on diverse microtubule cytoskeletal structures for its reproduction, multiplication, and dissemination. Due to the small size of this parasite, cytoskeleton has been primarily observable electron microscopy (EM). Here, we demonstrate that nanoscale organisation within reach using ultrastructure expansion (U-ExM). In developing microgametocytes, U-ExM allows monitoring dynamic assembly axonemes concomitant tubulin polyglutamylation...
SummaryCalcium-dependent protein kinases (CDPKs) play key regulatory roles in the life cycle of malaria parasite, but many cases their precise molecular functions are unknown. Using rodent parasite Plasmodium berghei, we show that CDPK1, which is known to be essential asexual blood stage expressed all stages and indispensable during sexual mosquito life-cycle stages. Knockdown CDPK1 resulted developmentally arrested parasites prevented transmission, these effects were independent previously...
Regulated exocytosis by secretory organelles is important for malaria parasite invasion and egress. Many effector proteins, including perforins, adhesins, proteases, are extensively proteolytically processed both pre- postexocytosis. Here we report the multistage antiplasmodial activity of aspartic protease inhibitor hydroxyl-ethyl-amine-based scaffold compound 49c. This inhibits preexocytosis processing several secreted rhoptry microneme proteins targeting corresponding maturases...
Transmission of malaria-causing parasites to mosquitoes relies on the production gametocyte stages and their development into gametes. These display various microtubule cytoskeletons architecture corresponding organisation centres (MTOC) remains elusive. Combining ultrastructure expansion microscopy (U-ExM) with bulk proteome labelling, we first reconstructed in 3D subpellicular network which confers cell rigidity Plasmodium falciparum gametocytes. Upon activation, as microgametocyte...
A membrane protein interacts with PKG and regulates calcium signals at multiple lifecycle stages in malaria parasites.
Bacterial populations are subject to complex processes of diversification that involve mutation and horizontal DNA transfer mediated by transformation, transduction, or conjugation. Tracing the evolutionary events leading genetic changes allows us infer history a microbe. Here, we combine experimental in silico approaches explore forces drive genome dynamics Streptococcus agalactiae, cause neonatal infections. We demonstrate large segments up 334 kb chromosome S. agalactiae can be...
Fertilization is a crucial yet poorly characterized event in eukaryotes. Our previous discovery that the broadly conserved protein HAP2 (GCS1) functioned gamete membrane fusion unicellular green alga Chlamydomonas and malaria pathogen Plasmodium led us to exploit rare biological phenomenon of isogamy comparative transcriptomics strategy uncover additional sexual reproduction genes. All previously identified fertilization-essential genes fell into related clusters based on their expression...
A major obstacle in analyzing gene function apicomplexan parasites is the absence of a practical regulatable expression system. Here, we identified functional transcriptional activation domains within Apicomplexan AP2 (ApiAP2) family transcription factors. These ApiAP2 transactivation were validated blood-, liver-, and mosquito-stage used to create robust conditional system for stage-specific, tetracycline-dependent regulation Toxoplasma gondii, Plasmodium berghei, falciparum. To demonstrate...
The transmission of malaria parasites to mosquitoes relies on the rapid induction sexual reproduction upon their ingestion into a blood meal. Haploid female and male gametocytes become activated emerge from host cells, males enter cell cycle produce eight microgametes. synchronized nature gametogenesis allowed us investigate phosphorylation signaling during its first minute in Plasmodium berghei via high-resolution time course phosphoproteome. This revealed an unexpectedly broad response,...
Summary Invasion of hepatocytes by sporozoites is essential for Plasmodium to initiate infection the mammalian host. The parasite's subsequent intracellular differentiation in liver first developmental step its cycle. Despite their biological significance, surprisingly little known signalling pathways required sporozoite invasion. We report that invasion requires through two second‐messengers – cGMP mediated cGMP‐dependent protein kinase (PKG), and Ca 2+ , calcium‐dependent 4 (CDPK4)....
In malaria parasites, evolution of parasitism has been linked to functional optimisation. Despite this optimisation, most members a calcium-dependent protein kinase (CDPK) family show genetic redundancy during erythrocytic proliferation. To identify relationships between phospho-signalling pathways, we here screen 294 interactions among kinases in Plasmodium berghei. This reveals synthetic negative interaction hypomorphic allele the G (PKG) and CDPK4 control erythrocyte invasion which is...
Malaria transmission relies on the production of gametes following ingestion by a mosquito. Here, we show that Ca2+-dependent protein kinase 4 controls three processes essential to progress from single haploid microgametocyte release eight flagellated microgametes in Plasmodium berghei. A myristoylated isoform is activated Ca2+ initiate first genome replication within twenty seconds activation. This role mediated SAPS-domain family involved S-phase entry. At same time, CDPK4 required for...
Cell cycle transitions are generally triggered by variation in the activity of cyclin-dependent kinases (CDKs) bound to cyclins. Malaria-causing parasites have a life with unique cell-division cycles, and repertoire divergent CDKs cyclins poorly understood function interdependency. We show that Plasmodium berghei CDK-related kinase 5 (CRK5), is critical regulator atypical mitosis gametogony required for mosquito transmission. It phosphorylates canonical CDK motifs components pre-replicative...
Kinetochores are multiprotein assemblies directing mitotic spindle attachment and chromosome segregation. In apicomplexan parasites, most known kinetochore components associated regulators apparently missing, suggesting a minimal structure with limited control over this study, we use interactomics combined deep homology searches to identify 13 previously unknown of kinetochores in Apicomplexa. Apicomplexan highly divergent sequence composition from animal fungal models. The nanoscale...
Abstract The Aurora family of kinases orchestrates chromosome segregation and cytokinesis during cell division, with precise spatiotemporal regulation its catalytic activities by distinct protein scaffolds. Plasmodium spp., the causative agents malaria, are unicellular eukaryotes three unique highly divergent aurora-related (ARK1-3) that essential for asexual cellular proliferation but lack most canonical scaffolds/activators. Here we investigate role ARK2 sexual rodent malaria berghei ,...
Abstract Malaria-causing parasites of the Plasmodium genus undergo multiple developmental phases in human and mosquito hosts, regulated by various post-translational modifications. While ubiquitination multi-component E3 ligases is key to regulate a wide range cellular processes eukaryotes, little known about its role . Here we show that berghei expresses conserved SKP1/Cullin1/FBXO1 (SCF FBXO1 ) complex showing tightly expression localisation across stages. It cell division for nuclear...
ABSTRACT Thirty-five putative integrative conjugative elements and related were identified at 15 locations in the eight sequenced genomes of Streptococcus agalactiae . Twelve are composite, likely resulting from site-specific accretions. Circular forms detected for five elements. Macroarray analysis confirmed their high plasticity wide distribution S.
Alveolins, or inner membrane complex (IMC) proteins, are components of the subpellicular network that forms a structural part pellicle malaria parasites. In Plasmodium berghei, deletions three alveolins, IMC1a, b, and h, each resulted in reduced mechanical strength gliding velocity ookinetes sporozoites. Using time lapse imaging, we show here deletion IMC1h (PBANKA_143660) also has an impact on directionality motility behaviour both Despite their marked defects, sporozoites lacking were able...