A5066458574- Malaria Research and Control
- Invertebrate Immune Response Mechanisms
- Mosquito-borne diseases and control
- CRISPR and Genetic Engineering
- Computational Drug Discovery Methods
- vaccines and immunoinformatics approaches
- Evolution and Genetic Dynamics
- Vector-borne infectious diseases
- Complement system in diseases
- Livestock and Poultry Management
- Bird parasitology and diseases
- Insect Resistance and Genetics
- Economic and Technological Innovation
- Innovation and Socioeconomic Development
- Protein Structure and Dynamics
- Metabolomics and Mass Spectrometry Studies
- Parasites and Host Interactions
- Photosynthetic Processes and Mechanisms
- Enzyme Structure and Function
- HIV/AIDS drug development and treatment
- Genomics and Phylogenetic Studies
- Machine Learning in Bioinformatics
- Immune Cell Function and Interaction
- Insect symbiosis and bacterial influences
- Toxin Mechanisms and Immunotoxins
Umeå University
2019-2025
Wellcome Sanger Institute
2013-2023
Imperial College London
2008-2014
Highlights•Two-thirds of Plasmodium berghei genes contribute to normal blood stage growth•The core genome malaria parasites is highly optimized for rapid host colonization•Essential parasite and pathways are identified drug target prioritization•Low functional redundancy reflects the constant environment encountered by a parasiteSummaryThe genomes contain many unknown function. To assist development through identification essential pathways, we have measured competitive growth rates in mice...
Malaria transmission to mosquitoes requires a developmental switch in asexually dividing blood-stage parasites sexual reproduction. In Plasmodium berghei, the transcription factor AP2-G is required and sufficient for this switch, but how particular sex determined haploid parasite remains unknown. Using global screen of barcoded mutants, we here identify genes essential formation either male or female forms validate their importance transmission. High-resolution single-cell transcriptomics...
Abstract Many Plasmodium genes remain uncharacterized due to low genetic tractability. Previous large-scale knockout screens have only been able target about half of the genome in more genetically tractable rodent malaria parasite berghei. To overcome this limitation, we developed a scalable CRISPR system called P. berghei high-throughput (PbHiT), which uses single cloning step generate targeting vectors with 100-bp homology arms physically linked guide RNA (gRNA) that effectively integrate...
Transmission from the vertebrate host to mosquito vector represents a major population bottleneck in malaria life cycle that can successfully be targeted by intervention strategies. However, date only about 25 parasite proteins expressed during this critical phase have been functionally analysed gene disruption. We describe first systematic, larger scale generation and phenotypic analysis of Plasmodium berghei knockout (KO) lines, characterizing 20 genes encoding putatively secreted...
The genome-wide identification of gene functions in malaria parasites is hampered by a lack reverse genetic screening methods. We present large-scale resource barcoded vectors with long homology arms for effective modification the Plasmodium berghei genome. Cotransfecting dozens into haploid blood stages creates complex pools mutants, whose competitive fitness can be measured during infection single mouse using barcode sequencing (barseq). To validate utility this resource, we rescreen P....
Plasmodium gene functions in mosquito and liver stages remain poorly characterized due to limitations the throughput of phenotyping at these stages. To fill this gap, we followed more than 1,300 barcoded P. berghei mutants through life cycle. We discover 461 genes required for efficient parasite transmission mosquitoes stage back into bloodstream mice. analyze screen context genomic, transcriptomic, metabolomic data by building a thermodynamic model liver-stage metabolism, which shows major...
The Plasmodium Genetic Modification (PlasmoGEM) database (http://plasmogem.sanger.ac.uk) provides access to a resource of modular, versatile and adaptable vectors for genome modification spp. parasites. PlasmoGEM currently consists >2000 plasmids designed modify the berghei, malaria parasite rodents, which can be requested by non-profit research organisations free charge. are with long homology arms efficient integration carry gene specific barcodes identify individual mutants. They used...
Avian malaria parasites are prevalent around the world and infect a wide diversity of bird species. Here, we report sequencing analysis high-quality draft genome sequences for two avian species, Plasmodium relictum gallinaceum . We identify 50 genes that specific to malaria, located in an otherwise conserved core shares gene synteny with all other sequenced genomes. Phylogenetic suggests species form outgroup mammalian using amino acid divergence between estimate avian- mammalian-infective...
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...
Synopsis Spiderweb‐like gelatine matrices generated by electrospinning are introduced as versatile substrate for culturing animal cell monolayers destined cryofixation and EM. Thus, non‐disruptive sampling transfer of native cells into high‐pressure freezing devices is possible within about 30 seconds. In addition to cryosection‐ replica‐labelling, this aproach can be applied various complementary microscopy biochemical methods.
Malaria represents a major global health issue, and the identification of new intervention targets remains an urgent priority. This search is hampered by more than one-third genes malaria-causing Plasmodium parasites being uncharacterized. We report large-scale protein interaction network in schizonts, generated combining blue native-polyacrylamide electrophoresis with quantitative mass spectrometry machine learning. integrative approach, spanning 3 species, identifies >20,000 putative...
Malaria parasites must undergo sexual and sporogonic development in mosquitoes before they can infect their vertebrate hosts. We report the discovery characterization of MISFIT, first protein with paternal effect on rodent malaria parasite Plasmodium berghei Anopheles mosquitoes. MISFIT is expressed male gametocytes localizes to nuclei gametocytes, zygotes ookinetes. Gene disruption results mutant ookinetes reduced genome content, microneme defects altered transcriptional profiles putative...
Abstract Many Plasmodium genes remain uncharacterised due to low genetic tractability. Previous large scale knockout screens have only been able target about half of the genome in more genetically tractable rodent malaria parasite berghei . To overcome this limitation, we developed a scalable CRISPR system called PbHiT, which uses single cloning step generate targeting vectors with 100 bp homology arms physically linked guide RNA (gRNA) that effectively integrate into locus. We show PbHiT...
Abstract Respiratory syncytial virus (RSV) is a major cause of respiratory morbidity, resulting in hospitalization for bronchiolitis some infected infants that associated with wheeze later life. Genetic factors are known to affect the severity sequelae after RSV infection, but complexity temporal and genetic effects makes it difficult analyze this response studies man. Therefore, we developed murine model occurring infection early Haplotype-based analysis interstrain differences identified...
The passage through the mosquito is a major bottleneck for malaria parasite populations and target of interventions aiming to block disease transmission. Here, we used DNA microarrays profile developmental transcriptomes rodent Plasmodium berghei in vivo, midgut Anopheles gambiae mosquitoes, from stages blood bolus sporulating oocysts on basal gut wall. Data analysis identified several distinct transcriptional programmes encompassing genes putatively involved processes or interactions with...
As the Plasmodium parasite transitions between mammalian and mosquito host, it has to adjust quickly new environments. Palmitoylation, a reversible dynamic lipid post-translational modification, plays central role in regulating this process been implicated with functions for morphology, motility host cell invasion. While proteins associated gliding machinery have described be palmitoylated, no palmitoyl transferase responsible previously identified. Here, we characterize two palmityol...
Summary All the pathology and symptoms associated with malaria are caused by growth of Plasmodium parasites inside human red blood cells. This process, which in case major pathogen falciparum takes place over a 48-hour period, involves multiple tightly regulated developmental transitions. Understanding P. genes that regulate these key processes could lead to identification targets for new drugs. However, while large-scale sequencing efforts have led good understanding genome how it evolves...
Summary The transmission of malaria parasites from vertebrate host to mosquito vector requires a developmental switch in asexually dividing blood-stage sexual reproduction. In Plasmodium berghei the transcription factor AP2-G is required and sufficient for this switch, but how particular sex determined haploid parasite remains unknown. Using global screen barcoded mutants, we here identify ten genes essential formation either male or female forms validate their importance transmission....
<ns4:p>The rodent parasite <ns4:italic>Plasmodium chabaudi </ns4:italic>is an important <ns4:italic>in vivo </ns4:italic>model of malaria. The ability to produce chronic infections makes it particularly useful for investigating the development anti-<ns4:italic>Plasmodium</ns4:italic> immunity, as well features associated with virulence during both acute and phases infection. <ns4:italic>P. chabaudi</ns4:italic> also undergoes asexual maturation (schizogony) erythrocyte invasion in culture,...
Abstract Avian malaria parasites are prevalent around the world, and infect a wide diversity of bird species. Here we report sequencing analysis high quality draft genome sequences for two avian species, Plasmodium relictum gallinaceum . We identify 50 genes that specific to malaria, located in an otherwise conserved core shares gene synteny with all other sequenced genomes. Phylogenetic suggests species form outgroup mammalian using amino acid divergence between estimate mammalian-infective...
<ns4:p>The rodent parasite <ns4:italic>Plasmodium chabaudi </ns4:italic>is an important <ns4:italic>in vivo </ns4:italic>model of malaria. The ability to produce chronic infections makes it particularly useful for investigating the development anti-<ns4:italic>Plasmodium</ns4:italic> immunity, as well features associated with virulence during both acute and phases infection. <ns4:italic>P. chabaudi</ns4:italic> also undergoes asexual maturation (schizogony) erythrocyte invasion in culture,...