A5066168804- Trypanosoma species research and implications
- Research on Leishmaniasis Studies
- Insect symbiosis and bacterial influences
- Lysosomal Storage Disorders Research
- Genetic and Kidney Cyst Diseases
- Chromosomal and Genetic Variations
- Malaria Research and Control
- Coccidia and coccidiosis research
- RNA and protein synthesis mechanisms
- Helminth infection and control
- Insect and Pesticide Research
- Parasitic Infections and Diagnostics
- Lung Cancer Treatments and Mutations
- Calcium signaling and nucleotide metabolism
- Microtubule and mitosis dynamics
- Legume Nitrogen Fixing Symbiosis
- Biochemical and Molecular Research
- Phytoplasmas and Hemiptera pathogens
- Science, Research, and Medicine
- Biomedical Research and Pathophysiology
- HER2/EGFR in Cancer Research
- Synthesis and biological activity
- Advanced Materials and Mechanics
- Complement system in diseases
- Nematode management and characterization studies
Oxford Brookes University
2019-2024
University of Oxford
2004-2019
University of Manchester
2000-2010
Cancer Research UK Manchester Institute
2007-2010
Paterson Public Schools
2008
Institute of Cancer Research
2007
Universidade Federal do Rio de Janeiro
1999
Trypanosoma brucei is a model trypanosomatid, an important group of human, animal and plant unicellular parasites. Understanding their complex cell architecture life cycle challenging because, as with most eukaryotic microbes, ~50% genome-encoded proteins have completely unknown functions. Here, using fluorescence microscopy lines expressing endogenously tagged proteins, we mapped the subcellular localization 89% T. proteome, resource call TrypTag. We provide clues to function define...
African trypanosomes are protozoan parasites that cause sleeping sickness in humans through a tsetse fly vector. The procyclic form of Trypanosoma brucei has single, attached flagellum describes helical path along the cell from posterior to anterior. During division, specific flagellum-flagellum connection is elaborated between new and old flagellum. This connector was present only during duplication found be involved replication pattern polarity. finding implicates concept cytotaxis...
Significance Cilia are highly conserved organelles present in most eukaryotic cell types. The transition zone (TZ) is a ciliary subdomain that acts as “gate” to control the composition of cilium. importance TZ reflected many human diseases (termed ciliopathies) caused by mutations complexes. Here, we use new proteomics technique find components African trypanosome TZ. We leverage extraordinary tractability this system investigate proteins, localizing them distinct subdomains within TZ, and...
Attachment to a substrate maintain position in specific ecological niche is common strategy across biology, especially for eukaryotic parasites. During development the sand fly vector, parasite Leishmania adheres stomodeal valve, as specialised haptomonad form. Dissection of adhesion critical step understanding complete life cycle . Nevertheless, studies are limited, this technically challenging form investigate. Here, we have combined three-dimensional electron microscopy approaches,...
Abstract Leishmania species, members of the kinetoplastid parasites, cause leishmaniasis, a neglected tropical disease, in millions people worldwide. has complex life cycle with multiple developmental forms, as it cycles between sand fly vector and mammalian host; understanding their is critical to disease spread. One key stages haptomonad form, which attaches insect tissues through its flagellum. This adhesion, conserved across implicated having an important function within hence...
The unicellular parasite Leishmania has a precisely defined cell architecture that is inherited by each subsequent generation, requiring highly coordinated pattern of duplication and segregation organelles cytoskeletal structures. A framework nuclear division morphological changes known from light microscopy, yet this limited resolution the intrinsic organisation within body their manner inheritance unknown. Using volume electron microscopy approaches, we have produced three-dimensional...
The distal end of the eukaryotic flagellum/cilium is important for axonemal growth and signaling has distinct biomechanical properties. Specific flagellum tip structures exist, yet their composition, dynamics, functions are largely unknown. We used biochemical approaches to identify seven constituents flagella connector at an assembling trypanosome three capping structure tips both mature flagella. Both contain evolutionarily conserved as well kinetoplastid-specific proteins, component...
Leishmania kinetoplastid parasites infect millions of people worldwide and have a distinct cellular architecture depending on location in the host or vector specific pathogenicity functions. An invagination cell body membrane at base flagellum, flagellar pocket (FP), is an iconic feature, central to processes that are critical for pathogenicity. The FP has bulbous region posterior collar distal neck where surrounds flagellum more closely. attached one side by short attachment zone (FAZ). We...
Adhesion to surfaces is a common strategy employed across biology, especially by pathogens. Within their sand fly vector, Leishmania parasites undergo multiple developmental stages, including the understudied haptomonad form, which adheres stomodeal valve via highly modified flagellum. This adhesion, likely critical for efficient transmission, mediated complex adhesion plaque from filaments in flagellum extend towards cell body and connect attachment zone (FAZ), cytoskeletal structure...
Abstract Within the human host, symptoms of malaria are caused by replication parasites within erythrocytes. Growth inside erythrocyte exposes to normal surveillance erythrocytes host organism, in particular clearance spleen. Here we show that parasite Plasmodium falciparum undergoes a rapid, multi-step metamorphosis transforms invasive merozoite into an amoeboid-shaped cell minutes after invading This transformation involves increase surface area and is mediated factors already present...
Throughout its elongation, the new flagellum of procyclic form African trypanosome Trypanosoma brucei is tethered at tip to lateral aspect old flagellum. This phenomenon provides a cytotactic mechanism for influencing inheritance cellular pattern. Here, we show that this tethering produced via discrete, mobile transmembrane junction – flagella connector. Light and electron microscopy reveal connector links extending microtubules three doublet in flagellar axoneme. Two sets filaments connect...
The 9 + 2 axoneme structure of the motile flagellum/cilium is an iconic, apparently symmetrical cellular structure. Recently, asymmetries along length flagella have been identified in a number organisms, typically inner and outer dynein arms. Flagellum-beat waveforms are adapted for different functions. They may start either near flagellar tip or its base be asymmetrical. We hypothesized that proximal/distal asymmetry molecular composition control site waveform initiation direction...
Trypanosomes and Leishmanias are important human parasites whose cellular architecture is centred on the single flagellum. In trypanosomes, this flagellum attached to cell along a complex attachment zone (FAZ), comprising flagellar cytoplasmic components, integrity of which required for correct morphogenesis division. The FAZ cytoskeleton conspicuously associated with sheet endoplasmic reticulum termed 'FAZ ER'. present work, 3D electron tomography bloodstream form trypanosomes was used...
Abstract Fanconi anemia (FA) is an inherited disease with congenital abnormalities and extreme risk of acute myeloid leukemia (AML). Genetic events occurring during malignant transformation in FA the biology FA‐associated AML are poorly understood, but often preceded by development chromosomal aberrations involving 3q26‐29 bone marrow patients. We report here molecular cytogenetic characterization FA‐derived cell lines SB1685CB SB1690CB conventional array comparative genomic hybridization,...
Most motile flagella have an axoneme that contains nine outer microtubule doublets and a central pair (CP) of microtubules. The CP coordinates the flagellar beat defects in projections are associated with motility human disease. nucleate near ‘basal plate’ at distal end transition zone (TZ). Here, we show trypanosome TZ protein ‘basalin’ is essential for building basal plate, its loss nucleation defects, inefficient recruitment assembly factors to TZ, flagellum paralysis. Guided by synteny,...
The apical complex of apicomplexan parasites is essential for host cell invasion and intracellular survival as the site regulated exocytosis from specialised secretory organelles called rhoptries micronemes. Despite its importance, there are few data on three-dimensional organisation quantification these within or how they trafficked to this region plasma membrane exocytosis. In coccidian apicomplexans an additional tubulin-containing hollow barrel structure, conoid, which provides a...
Gametogenesis in Plasmodium spp. occurs within the Anopheles mosquito and is essential for sexual reproduction / differentiation onwards transmission to mammalian hosts. To better understand 3D organisation of male gametogenesis, we used serial block face scanning electron microscopy (SBF-SEM) serial-section cellular tomography (ssET) P. berghei microgametocytes examine key structures during gamete formation. Our data reveals an elaborate axonemes coiling around nucleus opposite directions...
Flagella have multiple functions that are associated with different axonemal structures. Motile flagella typically a 9 + 2 arrangement of microtubules, whereas sensory normally 0 arrangement. Leishmania exhibits both these flagellum forms and differentiation between two is cytoskeletal cell shape changes. We disrupted elongation in by deleting the intraflagellar transport (IFT) protein IFT140 examined effects on morphogenesis. Δift140 cells no external flagellum, having only very short...
The shape and form of the flagellated eukaryotic parasite Leishmania is sculpted to its ecological niches needs be transmitted each generation with great fidelity. cell defined by sub-pellicular microtubule array positioning nucleus, kinetoplast flagellum within this array. emerges from anterior end body through an invagination membrane called flagellar pocket. Within pocket laterally attached side a cytoskeletal structure attachment zone (FAZ). During cycle single copy organelles duplicate...
Significance Centriole/basal body (BB) connections involve two concepts: a tether and linker. Studies have revealed essential components of the tether, while linker remain largely unknown. Here, we describe BBLP, trypanosome protein that is cytoskeletal component linker, localizing between BB pro-BB throughout cell cycle. Importantly, RNA interference (RNAi) depletion BBLP results in splitting BB–pro-BB pair subtending only new flagellum, perturbs mitochondrial DNA inheritance. Our data...
Abstract The apical complex of apicomplexan parasites is essential for host cell invasion and intracellular survival as the site regulated exocytosis from specialised secretory organelles called rhoptries micronemes. Despite its importance, there little data on three-dimensional organisation quantification these within or how they are trafficked to this region plasma membrane exocytosis. In coccidian apicomplexans an additional tubulin-containing hollow barrel structure, conoid, which...
Abstract Eukaryotic flagella - widely conserved structures involved in signalling, metabolism and motility – have a core microtubular axoneme that, many organisms, is accompanied by prominent extra-axonemal structures. In kinetoplastids, including human parasites such as trypanosomes Leishmania , dense filamentous lattice called the paraflagellar rod (PFR) accompanies for most of its length. While functional studies showed that presence PFR structure required normal motility, evaluation more...