A5061783232- Toxoplasma gondii Research Studies
- Trypanosoma species research and implications
- Malaria Research and Control
- Parasitic Infections and Diagnostics
- Cytomegalovirus and herpesvirus research
- Herpesvirus Infections and Treatments
- Mosquito-borne diseases and control
- Autophagy in Disease and Therapy
- Biochemical and Molecular Research
- Vector-borne infectious diseases
- Rabies epidemiology and control
- DNA Repair Mechanisms
- Cellular transport and secretion
- Invertebrate Immune Response Mechanisms
- Bacteriophages and microbial interactions
- Mitochondrial Function and Pathology
- Ubiquitin and proteasome pathways
- Nanoparticles: synthesis and applications
- Protist diversity and phylogeny
- Research on Leishmaniasis Studies
- Synthesis and Biological Evaluation
- Plant Virus Research Studies
- Viral Infections and Vectors
- Complement system in diseases
- interferon and immune responses
Wellcome Centre for Molecular Parasitology
2016-2024
University of Glasgow
2016-2024
Heidelberg University
2011-2019
University Hospital Heidelberg
2011-2019
Wellcome Trust
2016-2019
Instituto Nacional de Metrologia, Qualidade e Tecnologia
2015-2017
Universidade de Caxias do Sul
2016
National Institute of Science and Technology for Structural Biology and Bioimaging
2010-2015
Universidade Federal do Rio de Janeiro
2005-2011
Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro
2008-2010
Apicomplexan actin is important during the parasite's life cycle. Its polymerization kinetics are unusual, permitting only short, unstable F-actin filaments. It has not been possible to study in vivo and so its physiological roles have remained obscure, leading models distinct from conventional behaviour. Here a modified version of commercially available actin-chromobody was tested as novel tool for visualising dynamics Toxoplasma gondii. Cb labels filamentous structures within parasite...
Here, we provided the first evidence of Ag/AgCl-nanoparticles production in yeast strains from<italic>in vitro</italic>cultures.
Abstract Dentistry and orthopedics are undergoing a revolution in order to provide more reliable, comfortable long-lasting implants patients. Titanium (Ti) titanium alloys have been used dental total hip arthroplasty due their excellent biocompatibility. However, Ti-based human body suffer surface degradation (corrosion wear) resulting the release of metallic ions solid wear debris (mainly dioxide) leading peri-implant inflammatory reactions. Unfortunately, our current understanding...
The cystine-glutamate antiporter, xCT, supports a glutathione synthesis program enabling cancer cells to cope with metabolically stressful microenvironments. Up-regulated in combination glutaminolysis, leads increased extracellular glutamate, which promotes invasive behavior by activating metabotropic glutamate receptor 3 (mGluR3). Here we show that activation of mGluR3 breast activates Rab27-dependent release vesicles (EVs), can transfer characteristics “recipient” tumor cells. These EVs...
Abstract BH3-mimetics are a new class of anti-cancer drugs that inhibit anti-apoptotic Bcl-2 proteins. In doing so, sensitise to cell death. Venetoclax is potent, BCL-2 selective BH3-mimetic clinically approved for use in chronic lymphocytic leukaemia. has also been shown mitochondrial metabolism, this consistent with proposed role metabolic regulation. We used venetoclax understand function. Similar others, we found inhibited respiration. addition, impairs TCA cycle activity leading...
Erythrocyte invasion by merozoites forms of the malaria parasite is a key step in establishment human disease. To date, efforts to understand cellular events underpinning entry have been limited insights from non-human parasites, with no studies at sub-micrometer resolution undertaken using most virulent parasite, Plasmodium falciparum. This leaves our understanding dynamics merozoite sub-cellular compartments during infectionincomplete, particular that secretory organelles. Using advances...
Abstract Mitochondria distribution in cells controls cellular physiology health and disease. Here we describe the mitochondrial morphology positioning found different stages of lytic cycle eukaryotic single-cell parasite Toxoplasma gondii . The cycle, driven by tachyzoite life stage, is responsible for acute toxoplasmosis. It known that whilst inside a host cell maintains its single mitochondrion at periphery. We upon transition from to extracellular matrix, radically changes, resulting...
Apicomplexan parasites invade host cells in an active process involving their ability to move by gliding motility. While the acto-myosin system of parasite plays a crucial role formation and release attachment sites during this process, there are still open questions regarding involvement other mechanisms In many eukaryotes, secretory-endocytic cycle leads recycling receptors (integrins), necessary form sites, regulation surface area motility, generation retrograde membrane flow. Here, we...
The encystation process is a key step in Toxoplasma gondii life cycle, allowing the parasite to escape from host immune system and transmission among hosts. A detailed characterization of formation structure cyst stage essential for better knowledge toxoplasmosis. Here we isolated cysts mice brains analysed wall matrix organization using different electron microscopy techniques. Images obtained showed that presented filamentous aspect, with circular openings on its surface. filaments were...
The phylum Apicomplexa includes intracellular parasites causing immense global disease burden, the deadliest of them being human malaria parasite Plasmodium falciparum, which invades and replicates within erythrocytes. cytoskeletal protein actin is well conserved apicomplexans but divergent from mammalian actins, was primarily reported to function during host cell invasion. However, novel invasion mechanisms have been described for several apicomplexans, specific functions acto-myosin system...
Plasmodium sporozoites can move at high speed for several tens of minutes, which is essential the initial stage a malaria infection. The crescent-shaped on 2D substrates preferably in same direction circular paths giving raise to helical 3D matrices. Here we determined structural basis that underlies this type movement. Immature, non-motile were found lack subpellicular network required obtaining crescent parasite shape. In vitro, parasites moving favoured faster and more persistent than few...
Abstract Background The apicoplast is a plastid organelle derived from secondary endosymbiosis, containing biosynthetic pathways essential for the survival of apicomplexan parasites. Toxoplasma clearly possesses four membranes but in related Plasmodium spp. has variably been reported to have either three or membranes. Methods Cryo-electron tomography was employed image merozoites falciparum and berghei frozen their near-native state. Three-dimensional reconstructions revealed number...
Regulated protein secretion is required for malaria parasite life cycle progression and transmission between the mammalian host mosquito vector. During from to vector, exocytosis of highly specialised secretory vesicles, such as osmiophilic bodies, key dissolution red blood cell parasitophorous vacuole membranes enabling gamete egress. The positioning adhesins TRAP family, micronemes sporozoite surface, essential gliding motility host. Here we identify a conserved role putative pantothenate...
All cells are subject to structural damage that must be addressed for continued growth. A wide range of affects the genome, meaning multiple pathways have evolved repair or bypass resulting DNA lesions. Though many conserved, their presence function can reflect life style individual organisms. To identify genome maintenance in a divergent eukaryote and important parasite, Trypanosoma brucei, we performed RNAi screens genes survival following exposure alkylating agent methyl...
Switching of the Variant Surface Glycoprotein (VSG) in Trypanosoma brucei provides a crucial host immune evasion strategy that is catalysed both by transcription and recombination reactions, each operating within specialised telomeric VSG expression sites (ES). switching likely triggered events focused on single actively transcribed ES, from repertoire around 15, but nature such unclear. Here we show RNA-DNA hybrids, called R-loops, form preferentially sequences termed 70 bp repeats spread...
The single mitochondrion of apicomplexan protozoa is thought to be critical for all stages the life cycle, and a validated drug target against these important human veterinary parasites. In contrast other eukaryotes, replication tightly linked cell cycle. A key step in mitochondrial segregation fission event, which many eukaryotes occurs by action dynamins constricting outer membrane mitochondria from cytosolic face. To date, none components machinery have been identified validated. We...
The recent decline in global malaria burden has stimulated efforts toward Plasmodium falciparum elimination. Understanding the biology of transmission stages may provide opportunities to reduce or prevent onward mosquitoes. Immature P. stages, termed I IV gametocytes, sequester human bone marrow before release into circulation as mature stage V gametocytes. This process likely involves interactions between host receptors and potentially immunogenic adhesins on infected red blood cell (iRBC)...
The voltage-dependent anion channel (VDAC) is a ubiquitous in the outer membrane of mitochondrion with multiple roles protein, metabolite and small molecule transport. In mammalian cells, VDAC as part larger complex including inositol triphosphate receptor, has been shown to have role mediating contacts between mitochondria endoplasmic reticulum (ER). We identify pathogenic apicomplexan Toxoplasma gondii demonstrate its importance for parasite growth. show that involved protein import...
Abstract Background Glioblastomas have highly infiltrative growth patterns that contribute to recurrence and poor survival. Despite infiltration being a critical therapeutic target, no clinically useful therapies exist counter glioblastoma invasion. Here, we report inhibition of ataxia telangiectasia Rad 3 related kinase (ATR) reduces invasion cells through dysregulation cytoskeletal networks subsequent integrin trafficking. Methods Glioblastoma motility were assessed in vitro vivo response...
The intravacuolar network inside the parasitophorous vacuole of Toxoplasma gondii consists an intricate system membrane-limited tubules uncertain role in parasite development. We propose that it is important structural support to maintenance parasites characteristic rosette arrangement vacuole, rather than being associated with nutrient acquisition from host cell, as previously suggested. based our assumptions on observations made by field emission scanning electron microscopy epithelial...
Initiation of DNA replication depends upon recognition genomic sites, termed origins, by AAA+ ATPases. In prokaryotes a single factor binds each origin, whereas in eukaryotes this role is played six-protein origin complex (ORC). Why evolved multisubunit initiator, and the roles component, remains unclear. Trypanosoma brucei, an ancient unicellular eukaryote, only one ORC-related TbORC1/CDC6, has been identified sequence homology. Here we show that three TbORC1/CDC6-interacting factors also...
Ribonucleotides represent a threat to DNA genome stability and transmission. Two types of Ribonuclease H (RNase H) excise ribonucleotides when they form part the strand, or hydrolyse RNA it base-pairs with in structures termed R-loops. Loss either RNase is lethal mammals, whereas yeast survives absence both enzymes. H1 loss tolerated by parasite Trypanosoma brucei but no work has examined function H2. Here we show that T. H2 (TbRH2A) leads growth cell cycle arrest concomitant accumulation...
Article4 October 2019Open Access Source DataTransparent process Apicomplexan F-actin is required for efficient nuclear entry during host cell invasion Mario Del Rosario orcid.org/0000-0002-0430-1463 Wellcome Centre For Integrative Parasitology, Institute of Infection, Immunity & Inflammation, Glasgow Biomedical Research Centre, University Glasgow, UK Search more papers by this author Javier Periz Georgios Pavlou Advanced Biosciences, CNRS, UMR5309, INSERM U1209, Université Grenoble Alpes,...
Highlights•Loss of the repair protein kinase ATR in Trypanosoma brucei is lethal•Loss T. alters VSG coat expression needed for immune evasion•Monoallelic RNA polymerase I undermined by loss•ATR loss leads to subtelomeric VSGs, indicative recombinationSummaryTrypanosoma evades mammalian immunity using recombination switch its surface-expressed variant surface glycoprotein (VSG), while ensuring that only one many multigene sites are transcribed at a time. DNA activities have been implicated...