Publications
151 results found
Waldock J, Chandra NL, Lelieveld J, et al., 2013, The role of environmental variables on <i>Aedes albopictus</i> biology and chikungunya epidemiology, PATHOGENS AND GLOBAL HEALTH, Vol: 107, Pages: 224-241, ISSN: 2047-7724
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- Citations: 123
Lombardo F, Ghani Y, Kafatos FC, et al., 2013, Comprehensive genetic dissection of the hemocyte immune response in the malaria mosquito anopheles gambiae, PLoS Pathogens, Vol: 9, Pages: 1-11, ISSN: 1553-7366
Reverse genetics in the mosquito Anopheles gambiae by RNAi mediated gene silencing has led in recent years to an advanced understanding of the mosquito immune response against infections with bacteria and malaria parasites. We developed RNAi screens in An. gambiae hemocyte-like cells using a library of double-stranded RNAs targeting 109 genes expressed highly or specifically in mosquito hemocytes to identify novel regulators of the hemocyte immune response. Assays included phagocytosis of bacterial bioparticles, expression of the antimicrobial peptide CEC1, and basal and induced expression of the mosquito complement factor LRIM1. A cell viability screen was also carried out to assess dsRNA cytotoxicity and to identify genes involved in cell growth and survival. Our results identify 22 novel immune regulators, including proteins putatively involved in phagosome assembly and maturation (Ca2+ channel, v-ATPase and cyclin-dependent protein kinase), pattern recognition (fibrinogen-domain lectins and Nimrod), immune modulation (peptidase and serine protease homolog), immune signaling (Eiger and LPS-induced factor), cell adhesion and communication (Laminin B1 and Ninjurin) and immune homeostasis (Lipophorin receptor). The development of robust functional cell-based assays paves the way for genome-wide functional screens to study the mosquito immune response to infections with human pathogens.
Gendrin M, Christophides GK, 2013, The <i>Anopheles</i> Mosquito Microbiota and Their Impact on Pathogen Transmission, ANOPHELES MOSQUITOES - NEW INSIGHTS INTO MALARIA VECTORS, Editors: Manguin, Publisher: INTECH EUROPE, Pages: 525-548
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- Citations: 52
Waldock J, Olson KE, Christophides GK, 2012, <i>Anopheles gambiae</i> Antiviral Immune Response to Systemic O'nyong-nyong Infection, PLOS NEGLECTED TROPICAL DISEASES, Vol: 6, ISSN: 1935-2735
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- Citations: 57
Midega JT, Smith DL, Olotu A, et al., 2012, Wind direction and proximity to larval sites determines malaria risk in Kilifi District in Kenya, NATURE COMMUNICATIONS, Vol: 3, ISSN: 2041-1723
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- Citations: 56
Megy K, Emrich SJ, Lawson D, et al., 2012, VectorBase: improvements to a bioinformatics resource for invertebrate vector genomics, NUCLEIC ACIDS RESEARCH, Vol: 40, Pages: D729-D734, ISSN: 0305-1048
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- Citations: 130
MacCallum RM, Redmond SN, Christophides GK, 2011, An expression map for <i>Anopheles gambiae</i>, BMC GENOMICS, Vol: 12, ISSN: 1471-2164
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- Citations: 19
Mendes AM, Awono-Ambene PH, Nsango SE, et al., 2011, Infection Intensity-Dependent Responses of <i>Anopheles gambiae</i> to the African Malaria Parasite <i>Plasmodium falciparum</i>, INFECTION AND IMMUNITY, Vol: 79, Pages: 4708-4715, ISSN: 0019-9567
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- Citations: 42
Christophides G, 2011, Contributions made by the Anopheles and Aedes Genome Projects, TROPICAL MEDICINE & INTERNATIONAL HEALTH, Vol: 16, Pages: 54-54, ISSN: 1360-2276
Povelones M, Upton LM, Sala KA, et al., 2011, Structure-Function Analysis of the <i>Anopheles gambiae</i> LRIM1/APL1C Complex and its Interaction with Complement C3-Like Protein TEP1, PLOS PATHOGENS, Vol: 7, ISSN: 1553-7366
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- Citations: 64
White BJ, Lawniczak MKN, Cheng C, et al., 2011, Adaptive divergence between incipient species of Anopheles gambiae increases resistance to <i>Plasmodium</i>, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 108, Pages: 244-249, ISSN: 0027-8424
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- Citations: 78
Baum J, Billker O, Bousema T, et al., 2011, A Research Agenda for Malaria Eradication: Basic Science and Enabling Technologies, PLOS MEDICINE, Vol: 8, ISSN: 1549-1676
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- Citations: 37
Magnusson K, Mendes AM, Windbichler N, et al., 2011, Transcription Regulation of Sex-Biased Genes during Ontogeny in the Malaria Vector Anopheles gambiae, Plos One, Vol: 6
Churcher TS, Dawes EJ, Sinden RE, et al., 2010, Population biology of malaria within the mosquito: density-dependent processes and potential implications for transmission-blocking interventions, MALARIA JOURNAL, Vol: 9, ISSN: 1475-2875
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- Citations: 27
Lawniczak MKN, Emrich SJ, Holloway AK, et al., 2010, Widespread Divergence Between Incipient <i>Anopheles gambiae</i> Species Revealed by Whole Genome Sequences, SCIENCE, Vol: 330, Pages: 512-514, ISSN: 0036-8075
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- Citations: 210
Neafsey DE, Lawniczak MKN, Park DJ, et al., 2010, SNP Genotyping Defines Complex Gene-Flow Boundaries Among African Malaria Vector Mosquitoes, SCIENCE, Vol: 330, Pages: 514-517, ISSN: 0036-8075
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- Citations: 134
Bartholomay LC, Waterhouse RM, Mayhew GF, et al., 2010, Pathogenomics of <i>Culex quinquefasciatus</i> and Meta-Analysis of Infection Responses to Diverse Pathogens, SCIENCE, Vol: 330, Pages: 88-90, ISSN: 0036-8075
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- Citations: 124
Waterhouse RM, Povelones M, Christophides GK, 2010, Sequence-structure-function relations of the mosquito leucine-rich repeat immune proteins, BMC GENOMICS, Vol: 11, ISSN: 1471-2164
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- Citations: 47
Cromer D, Christophides GK, Stark J, 2010, Hidden variable analysis of transcription factor cooperativity from microarray time courses, IET SYSTEMS BIOLOGY, Vol: 4, Pages: 131-U5561, ISSN: 1751-8849
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- Citations: 2
Meister S, Agianian B, Turlure F, et al., 2009, Anopheles gambiae PGRPLC-mediated defense against bacteria modulates infections with malaria parasites, PLoS Pathogens, Vol: 5, Pages: 1-13, ISSN: 1553-7366
Recognition of peptidoglycan (PGN) is paramount for insect antibacterial defenses. In the fruit fly Drosophila melanogaster, the transmembrane PGN Recognition Protein LC (PGRP-LC) is a receptor of the Imd signaling pathway that is activated after infection with bacteria, mainly Gram-negative (Gram−). Here we demonstrate that bacterial infections of the malaria mosquito Anopheles gambiae are sensed by the orthologous PGRPLC protein which then activates a signaling pathway that involves the Rel/NF-κB transcription factor REL2. PGRPLC signaling leads to transcriptional induction of antimicrobial peptides at early stages of hemolymph infections with the Gram-positive (Gram+) bacterium Staphylococcus aureus, but a different signaling pathway might be used in infections with the Gram− bacterium Escherichia coli. The size of mosquito symbiotic bacteria populations and their dramatic proliferation after a bloodmeal, as well as intestinal bacterial infections, are also controlled by PGRPLC signaling. We show that this defense response modulates mosquito infection intensities with malaria parasites, both the rodent model parasite, Plasmodium berghei, and field isolates of the human parasite, Plasmodium falciparum. We propose that the tripartite interaction between mosquito microbial communities, PGRPLC-mediated antibacterial defense and infections with Plasmodium can be exploited in future interventions aiming to control malaria transmission. Molecular analysis and structural modeling provided mechanistic insights for the function of PGRPLC. Alternative splicing of PGRPLC transcripts produces three main isoforms, of which PGRPLC3 appears to have a key role in the resistance to bacteria and modulation of Plasmodium infections. Structural modeling indicates that PGRPLC3 is capable of binding monomeric PGN muropeptides but unable to initiate dimerization with other isoforms. A dual role of this isoform is hypothesized: it sequesters monomeric PGN dampening weak
Bushell ESC, Ecker A, Schlegelmilch T, et al., 2009, Paternal effect of the nuclear formin-like protein MISFIT on plasmodium development in then mosquito vector, PLoS Pathogens, Vol: 5, Pages: 1-13, ISSN: 1553-7366
Malaria parasites must undergo sexual and sporogonic development in mosquitoes before they can infect their vertebrate hosts. We report the discovery and characterization of MISFIT, the first protein with paternal effect on the development of the rodent malaria parasite Plasmodium berghei in Anopheles mosquitoes. MISFIT is expressed in male gametocytes and localizes to the nuclei of male gametocytes, zygotes and ookinetes. Gene disruption results in mutant ookinetes with reduced genome content, microneme defects and altered transcriptional profiles of putative cell cycle regulators, which yet successfully invade the mosquito midgut. However, developmental arrest ensues during the ookinete transformation to oocysts leading to malaria transmission blockade. Genetic crosses between misfit mutant parasites and parasites that are either male or female gamete deficient reveal a strict requirement for a male misfit allele. MISFIT belongs to the family of formin-like proteins, which are known regulators of the dynamic remodeling of actin and microtubule networks. Our data identify the ookinete-to-oocyst transition as a critical cell cycle checkpoint in Plasmodium development and lead us to hypothesize that MISFIT may be a regulator of cell cycle progression. This study offers a new perspective for understanding the male contribution to malaria parasite development in the mosquito vector.
Megy K, Aarensburger P, Atkinson P, et al., 2009, VectorBase, Resource Center for Invertebrate Vectors of Human Pathogens, INFECTION GENETICS AND EVOLUTION, Vol: 9, Pages: 371-371, ISSN: 1567-1348
Povelones M, Waterhouse RM, Kafatos FC, et al., 2009, Leucine-Rich Repeat Protein Complex Activates Mosquito Complement in Defense Against <i>Plasmodium</i> Parasites, SCIENCE, Vol: 324, Pages: 258-261, ISSN: 0036-8075
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- Citations: 186
Lawson D, Arensburger P, Atkinson P, et al., 2009, VectorBase: a data resource for invertebrate vector genomics, NUCLEIC ACIDS RESEARCH, Vol: 37, Pages: D583-D587, ISSN: 0305-1048
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- Citations: 193
Muskavitch M, Neafsey D, Lawniczak M, et al., 2008, DEVELOPMENT OF A HIGH-DENSITY SNP GENOTYPING ARRAY FOR THE VECTOR MOSQUITO <i>ANOPHELES GAMBIAE</i>, BY THE AGSNP CONSORTIUM, 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene, Publisher: AMER SOC TROP MED & HYGIENE, Pages: 316-316, ISSN: 0002-9637
Turlure F, Waldock J, Meister S, et al., 2008, The <i>Anopheles</i> REL1 signaling pathway is required for anti-fungal immunity and can reduce malaria infections, Joint Conference of the 33rd FEBS Congress/11th IUBMB Conference, Publisher: BLACKWELL PUBLISHING, Pages: 277-277, ISSN: 1742-464X
Habtewold T, Povelones M, Blagborough AM, et al., 2008, Transmission blocking immunity in the malaria non-vector mosquito Anopheles quadriannulatus species A, Plos Pathogens, Vol: 4, ISSN: 1553-7374
Despite being phylogenetically very close to Anopheles gambiae, the major mosquito vector of human malaria in Africa,Anopheles quadriannulatus is thought to be a non-vector. Understanding the difference between vector and non-vectormosquitoes can facilitate development of novel malaria control strategies. We demonstrate that An. quadriannulatus islargely resistant to infections by the human parasite Plasmodium falciparum, as well as by the rodent parasite Plasmodiumberghei. By using genetics and reverse genetics, we show that resistance is controlled by quantitative heritable traits andmanifested by lysis or melanization of ookinetes in the mosquito midgut, as well as by killing of parasites at subsequentstages of their development in the mosquito. Genes encoding two leucine-rich repeat proteins, LRIM1 and LRIM2, and thethioester-containing protein, TEP1, are identified as essential in these immune reactions. Their silencing completelyabolishes P. berghei melanization and dramatically increases the number of oocysts, thus transforming An. quadriannulatusinto a highly permissive parasite host. We hypothesize that the mosquito immune system is an important cause of naturalrefractoriness to malaria and that utilization of this innate capacity of mosquitoes could lead to new methods to controltransmission of the disease.
Mendes AM, Schlegelmilch T, Cohuet A, et al., 2008, Conserved mosquito/parasite interactions affect development of Plasmodium falciparum in Africa, PLoS Pathogens, Vol: 4, Pages: 1-12, ISSN: 1553-7366
In much of sub-Saharan Africa, the mosquito Anopheles gambiae is the main vector of the major human malaria parasite, Plasmodium falciparum. Convenient laboratory studies have identified mosquito genes that affect positively or negatively the developmental cycle of the model rodent parasite, P. berghei. Here, we use transcription profiling and reverse genetics to explore whether five disparate mosquito gene regulators of P. berghei development are also pertinent to A. gambiae/P. falciparum interactions in semi-natural conditions, using field isolates of this parasite and geographically related mosquitoes. We detected broadly similar albeit not identical transcriptional responses of these genes to the two parasite species. Gene silencing established that two genes affect similarly both parasites: infections are hindered by the intracellular local activator of actin cytoskeleton dynamics, WASP, but promoted by the hemolymph lipid transporter, ApoII/I. Since P. berghei is not a natural parasite of A. gambiae, these data suggest that the effects of these genes have not been drastically altered by constant interaction and co-evolution of A. gambiae and P. falciparum; this conclusion allowed us to investigate further the mode of action of these two genes in the laboratory model system using a suite of genetic tools and infection assays. We showed that both genes act at the level of midgut invasion during the parasite's developmental transition from ookinete to oocyst. ApoII/I also affects the early stages of oocyst development. These are the first mosquito genes whose significant effects on P. falciparum field isolates have been established by direct experimentation. Importantly, they validate for semi-field human malaria transmission the concept of parasite antagonists and agonists.
Jaubert-Possamai S, Le Trionnaire G, Bonhomme J, et al., 2007, Gene knockdown by RNAi in the pea aphid <i>Acyrthosiphon pisum</i>, BMC BIOTECHNOLOGY, Vol: 7
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- Citations: 162
Pindyurin AV, Moorman C, de Wit E, et al., 2007, SUUR joins separate subsets of PcG, HP1 and B-type lamin targets in <i>Drosophila</i>, JOURNAL OF CELL SCIENCE, Vol: 120, Pages: 2344-2351, ISSN: 0021-9533
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- Citations: 45
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