A5006508100- Invertebrate Immune Response Mechanisms
- Malaria Research and Control
- Insect symbiosis and bacterial influences
- Mosquito-borne diseases and control
- Neurobiology and Insect Physiology Research
- Insect Resistance and Genetics
- Aquaculture disease management and microbiota
- Trypanosoma species research and implications
- Ion Transport and Channel Regulation
- Parasites and Host Interactions
- Complement system in diseases
- CRISPR and Genetic Engineering
- vaccines and immunoinformatics approaches
- Plant Reproductive Biology
- RNA and protein synthesis mechanisms
- Parasitic Infections and Diagnostics
- Plant Molecular Biology Research
- RNA Interference and Gene Delivery
- Coccidia and coccidiosis research
- Viral Infectious Diseases and Gene Expression in Insects
Imperial College London
2009-2023
Cyprus Institute
2014-2021
The London College
2013
Walter and Eliza Hall Institute of Medical Research
2009
University of Geneva
2007
University of California, Riverside
2007
Johns Hopkins University
2007
European Molecular Biology Laboratory
2004-2005
European Molecular Biology Laboratory
2002-2005
Leiden University Medical Center
2004
We have identified 242 Anopheles gambiae genes from 18 gene families implicated in innate immunity and detected marked diversification relative to Drosophila melanogaster. Immune-related involved recognition, signal modulation, effector systems show a deficit of orthologs excessive expansions, possibly reflecting selection pressures different pathogens encountered these insects' very life-styles. In contrast, the multifunctional Toll transduction pathway is substantially conserved,...
Mosquitoes are vectors of parasitic and viral diseases immense importance for public health. The acquisition the genome sequence yellow fever Dengue vector, Aedes aegypti (Aa), has enabled a comparative phylogenomic analysis insect immune repertoire: in Aa, malaria vector Anopheles gambiae (Ag), fruit fly Drosophila melanogaster (Dm). Analysis signaling pathways response modules reveals both conservative rapidly evolving features associated with different functional gene categories...
Techniques for targeted genetic disruption in Plasmodium, the causative agent of malaria, are currently intractable those genes that essential blood stage development. The ability to use RNA interference (RNAi) silence gene expression would provide a powerful means gain valuable insight into pathogenic stages but its functionality Plasmodium remains controversial. Here we have used various RNA-based silencing approaches test utility RNAi malaria parasites and undertaken an extensive...
Invasion of the Anopheles mosquito midgut by Plasmodium ookinete is a critical step in malaria transmission cycle. We have generated fluorescent P. berghei transgenic line that expresses GFP and oocyst stages, used it to perform first real-time analysis invasion living as well explanted intact midguts whose basolateral plasma membranes were vitally stained. These studies permitted detailed parasite motile behaviour cell biological process. Throughout its journey, displays distinct modes...
Summary An essential, but poorly understood part of malaria transmission by mosquitoes is the development ookinetes into sporozoite‐producing oocysts on mosquito midgut wall. For successful oocyst formation newly formed in lumen must enter, traverse, and exit epithelium to reach basal lamina, processes collectively known as invasion. After invasion ookinete‐to‐oocyst transition occur, a process believed require ookinete interactions with lamina components. Here, we report novel extracellular...
In much of sub-Saharan Africa, the mosquito Anopheles gambiae is main vector major human malaria parasite, Plasmodium falciparum. Convenient laboratory studies have identified genes that affect positively or negatively developmental cycle model rodent P. berghei. Here, we use transcription profiling and reverse genetics to explore whether five disparate gene regulators berghei development are also pertinent A. gambiae/P. falciparum interactions in semi-natural conditions, using field...
Malaria remains a devastating disease despite efforts at control and prevention. Extensive studies using mostly rodent infection models reveal that successful Plasmodium parasite transmission by the African mosquito vector Anopheles gambiae depends on finely tuned vector-parasite interactions. Here we investigate transcriptional response of A. to geographically related falciparum populations various intensities different stages. These responses are compared with those mosquitoes infected...
After being ingested by a female Anopheles mosquito during bloodmeal on an infected host, and before they can reach the salivary glands to be transmitted new Plasmodium parasites must establish infection of midgut in form oocysts. To achieve this, first survive series robust innate immune responses that take place prior to, during, immediately after ookinete traversal epithelium. Understanding how may evade these could highlight ways block malaria transmission. We show sporozoite surface...
We have developed an in vitro culture system for early sporogonic stages of Plasmodium berghei, which can be used to study developmental events normally taking place the midgut infected mosquito. These include penetration insect cells by mature ookinete, transformation into oocysts and development latter, sustained through several rounds nuclear division. The system, based upon co-culture enriched ookinetes with established cell lines, was mutant lacking both Pbs21 Pbs25 surface proteins....
Abstract The malaria parasite replicates asexually in the red blood cells of its vertebrate host employing epigenetic mechanisms to regulate gene expression response changes environment. We used chromatin immunoprecipitation followed by sequencing conjunction with RNA create an epigenomic and transcriptomic map developmental transition from asexual stages male female gametocytes ookinetes rodent Plasmodium berghei . Across examined, heterochromatin protein 1 associates variantly expressed...
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...
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...
Abstract Malaria is a mosquito-borne disease affecting millions of people every year. The rodent parasite Plasmodium berghei has served as model for human malaria transmission studies and played pivotal role in dissecting the mosquito immune response against infection. 6-cysteine protein P47, known to be important P. female gamete fertility, shown serve different function falciparum , protecting ookinetes from response. Here, we investigate P47 Anopheles gambiae infections. We show that...
Malaria remains one of the most devastating infectious diseases. Reverse genetic screens offer a powerful approach to identify genes and molecular processes governing malaria parasite biology. However, complex regulation gene expression genotype-phenotype associations in mosquito vector, along with sexual reproduction, have hindered development this critical part life cycle. To address this, we developed rodent Plasmodium berghei that, combination barcode sequencing, circumvents...
ABSTRACT Mosquito midgut stages of the malaria parasite present an attractive biological system to study host-parasite interactions and develop interventions block disease transmission. infection ensues upon oocyst development that follows ookinete invasion traversal mosquito epithelium. Here, we report characterization PIMMS2 ( Plasmodium screen candidate 2), a berghei protein with structural similarities subtilisin-like proteins. orthologs are in genomes all plasmodia mapped between...
Plasmodium falciparum malaria remains a major cause of global morbidity and mortality, mainly in sub-Saharan Africa. The numbers new cases deaths have been stable the last years despite intense efforts for disease elimination, highlighting need approaches to stop transmission. Further understanding parasite transmission biology could provide framework development such approaches. We phenotypically functionally characterized three novel genes, PIMMS01 , PIMMS57 PIMMS22 using targeted...
Abstract We report the isolation, full sequence characterization, amplification and expression properties of medfly chorion genes corresponding to autosomal locus Drosophila. These are found adjacent paramyosin gene organized in same order tandem orientation as their Drosophila homologues, although they spaced further apart. They show substantial divergence from including novel peptide repeats a new spacing tyrosines, which known be cross-linked Dipteran chorion. The amplified expressed...
The malaria parasite develops sexually in the mosquito midgut upon entry with ingested blood meal before it can invade epithelium and embark on sporogony. Recent data have identified a number of distinct transcriptional programmes operating during this critical phase life cycle. We aimed at characterizing parental contribution to these establish genetic framework that would guide further studies Plasmodium zygotic development ookinete-to-oocyst transition. To achieve we used vitro vivo...
Vitellogenesis and oocyte maturation require anautogenous female Anopheles mosquitoes to obtain a bloodmeal from vertebrate host. The is rich in proteins that are readily broken down into amino acids the midgut lumen absorbed by epithelial cells where they converted lipids then transported other tissues including ovaries. stearoyl-CoA desaturase (SCD) plays pivotal role this process converting saturated (SFAs) unsaturated (UFAs) fatty acids; latter being essential for maintaining cell...