Imperial College London

Professor George K. Christophides

Faculty of Natural SciencesDepartment of Life Sciences

Professor of Infectious Diseases & Immunity
 
 
 
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Contact

 

+44 (0)20 7594 5342g.christophides

 
 
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Location

 

6167Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

128 results found

Fofana A, Gendrin M, Sangare I, Sanou S, Wangraoua S, Drabo A, Christophides G, Ouedraogo JB, Yerbanga RSet al., 2015, CHARACTERIZATION AND ANTIBIORESISTANCE OF CULTURABLE MICROFLORA BACTERIA IN THE MIDGUT OF ADULT ANOPHELES GAMBIAE AND AN. COLUZZII, Publisher: AMER SOC TROP MED & HYGIENE, Pages: 264-265, ISSN: 0002-9637

Conference paper

Povelones M, Farrant KV, Christophides GK, 2015, STIMULATION OF A SERINE PROTEASE TARGETING THE LRIM1/APL1C COMPLEX REVEALS SPECIFICITY IN COMPLEMENT-LIKE PATHWAY ACTIVATION IN ANOPHELES GAMBIAE, Publisher: AMER SOC TROP MED & HYGIENE, Pages: 417-417, ISSN: 0002-9637

Conference paper

Habtewold T, Groom Z, Duchateau L, Christophides GKet al., 2015, Detection of viable Plasmodium ookinetes in the midguts of Anopheles coluzzi using PMA-qrtPCR, Parasites & Vectors, Vol: 8, ISSN: 1756-3305

BackgroundMosquito infection with malaria parasites depends on complex interactions between the mosquito immune response, the parasite developmental program and the midgut microbiota. Simultaneous monitoring of the parasite and bacterial dynamics is important when studying these interactions. PCR based methods of genomic DNA (gDNA) have been widely used, but their inability to discriminate between live and dead cells compromises their application. The alternative method of quantification of mRNA mainly reports on cell activity rather than density.MethodQuantitative real-time (qrt) PCR in combination with Propidium Monoazide (PMA) treatment (PMA-qrtPCR) has been previously used for selectively enumerating viable microbial cells. PMA penetrates damaged cell membranes and intercalates in the DNA inhibiting its PCR amplification. Here, we tested the potential of PMA-qrtPCR to discriminate between and quantify live and dead Plasmodium berghei malarial parasites and commensal bacteria in the midgut of Anopheles coluzzii Coetzee & Wilkerson 2013 (formerly An. gambiae M-form).ResultsBy combining microscopic observations with reverse transcriptase PCR (RT-PCR) we reveal that, in addition to gDNA, mRNA from dead parasites also persists inside the mosquito midgut, therefore its quantification cannot accurately reflect live-only parasites at the time of monitoring. In contrast, pre-treating the samples with PMA selectively inhibited qrtPCR amplification of parasite gDNA, with about 15 cycles (Ct-value) difference between PMA-treated and control samples. The limit of detection corresponds to 10 Plasmodium ookinetes. Finally, we show that the PMA-qrtPCR method can be used to quantify bacteria that are present in the mosquito midgut.ConclusionThe PMA-qrtPCR is a suitable method for quantification of viable parasites and bacteria in the midgut of Anopheles mosquitoes. The method will be valuable when studying the molecular interactions between the mosquito, the malaria parasite

Journal article

Abay SM, Dahiya N, Dembo E, Dori G, Christophides G, Esposito F, Lucantoni L, Lupidi G, Ogboi S, Ouedraogo R, Ouedraogo J-B, Sinisi A, Taglialatela-Scafati O, Yerbanga S, Habluetzel Aet al., 2015, Malaria transmission blocking activity of sesquiterpene lactones from Vernonia amygdalina, TROPICAL MEDICINE & INTERNATIONAL HEALTH, Vol: 20, Pages: 150-151, ISSN: 1360-2276

Journal article

Dahiya N, Tapanelli S, Chianese G, Abay SM, Taglialatela-Scafati O, Esposito F, Lupidi G, Christophides G, Lucantoni L, Yerbanga SR, Habluetzel Aet al., 2015, Transmission blocking effects of Azadirachta indica limonoids on early sporogonic development of Plasmodium: activity and bioavailability of seed fractions and isolated compounds, TROPICAL MEDICINE & INTERNATIONAL HEALTH, Vol: 20, Pages: 178-179, ISSN: 1360-2276

Journal article

Ukegbu CV, Cho J-S, Christophides GK, Vlachou Det al., 2015, Transcriptional silencing and activation of paternal DNA during Plasmodium berghei zygotic development and transformation to oocyst, Cellular Microbiology, Vol: 17, Pages: 1230-1240, ISSN: 1462-5822

The malaria parasite develops sexually in the mosquito midgut upon entry with the ingested blood meal before it can invade the midgut epithelium and embark on sporogony. Recent data have identified a number of distinct transcriptional programmes operating during this critical phase of the parasite life cycle. We aimed at characterizing the parental contribution to these transcriptional programmes and establish the genetic framework that would guide further studies of Plasmodium zygotic development and ookinete-to-oocyst transition. To achieve this we used in vitro and in vivo cross-fertilization experiments of various parasite lines expressing fluorescent reporters under the control of constitutive and stage-specific promoters. The results revealed that the zygote/ookinete stage exhibits a maternal phenotype with respect to constitutively expressed reporters, which is derived from either maternal mRNA inheritance or transcription of the maternal allele. The respective paternal alleles are silenced in the zygote/ookinete but reactivated after midgut invasion and transformation to oocyst. Transcripts specifically produced in the zygote/ookinete are synthesized de novo by both parental alleles. These findings highlight a putative role of epigenetic regulation of Plasmodium zygotic development and add substantially to the emerging picture of the molecular mechanisms regulating this important stage of malaria transmission.

Journal article

Abay SM, Lucantoni L, Dahiya N, Dori G, Dembo EG, Esposito F, Lupidi G, Ogboi S, Ouedraogo RK, Sinisi A, Taglialatela-Scafati O, Yerbanga RS, Bramucci M, Quassinti L, Ouedraogo JB, Christophides G, Habluetzel Aet al., 2015, Plasmodium transmission blocking activities of Vernonia amygdalina extracts and isolated compounds, MALARIA JOURNAL, Vol: 14, ISSN: 1475-2875

Journal article

Parham PE, Waldock J, Christophides GK, Hemming D, Agusto F, Evans KJ, Fefferman N, Gaff H, Gumel A, LaDeau S, Lenhart S, Mickens RE, Naumova EN, Ostfeld RS, Ready PD, Thomas MB, Velasco-Hernandez J, Michael Eet al., 2015, Climate, environmental and socio-economic change: weighing up the balance in vector-borne disease transmission, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 370, ISSN: 0962-8436

Journal article

Parham PE, Waldock J, Christophides GK, Michael Eet al., 2015, Climate change and vector-borne diseases of humans Preface, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 370, ISSN: 0962-8436

Journal article

Proestos Y, Christophides GK, Erguler K, Tanarhte M, Waldock J, Lelieveld Jet al., 2015, Present and future projections of habitat suitability of the Asian tiger mosquito, a vector of viral pathogens, from global climate simulation, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 370, ISSN: 0962-8436

Journal article

Dembo EG, Abay SM, Dahiya N, Ogboi JS, Christophides GK, Lupidi G, Chianese G, Lucantoni L, Habluetzel Aet al., 2015, Impact of repeated NeemAzal (R)-treated blood meals on the fitness of Anopheles stephensi mosquitoes, Parasites & Vectors, Vol: 8, ISSN: 1756-3305

Background: Herbal remedies are widely used in many malaria endemic countries to treat patients, in particular in theabsence of anti-malarial drugs and in some settings to prevent the disease. Herbal medicines may be specifically designedfor prophylaxis and/or for blocking malaria transmission to benefit both, the individual consumer and the community atlarge. Neem represents a good candidate for this purpose due to its inhibitory effects on the parasite stages that causethe clinical manifestations of malaria and on those responsible for infection in the vector. Furthermore, neem secondarymetabolites have been shown to interfere with various physiological processes in insect vectors. This studywas undertaken to assess the impact of the standardised neem extract NeemAzal® on the fitness of the malariavector Anopheles stephensi following repeated exposure to the product through consecutive blood meals ontreated mice.Methods: Batches of An. stephensi mosquitoes were offered 5 consecutive blood meals on female BALB/cmice treated with NeemAzal® at an azadirachtin A concentration of 60, 105 or 150 mg/kg. The blood feedingcapacity was estimated by measuring the haematin content of the rectal fluid excreted by the mosquitoesduring feeding. The number of eggs laid was estimated by image analysis and their hatchability assessed bydirect observations.Results: A dose and frequency dependent impact of NeemAzal® treatment on the mosquito feeding capacity,oviposition and egg hatchability was demonstrated. In the 150 mg/kg treatment group, the mosquito feedingcapacity was reduced by 50% already at the second blood meal and by 50 to 80% in all treatment groups atthe fifth blood meal. Consequently, a 50 – 65% reduction in the number of eggs laid per female mosquitowas observed after the fifth blood meal in all treatment groups. Similarly, after the fifth treated blood mealexposure, hatchability was found to be reduced by 62% and 70% in the 105 and 150 mg/kg group re

Journal article

Dembo EG, Abay SM, Dahiya N, Ogboi JS, Christophides GK, Lupidi G, Chianese G, Lucantoni L, Habluetzel Aet al., 2015, Impact of repeated NeemAzal-treated blood meals on the fitness of Anopheles stephensi mosquitoes., Parasit Vectors, Vol: 8

BACKGROUND: Herbal remedies are widely used in many malaria endemic countries to treat patients, in particular in the absence of anti-malarial drugs and in some settings to prevent the disease. Herbal medicines may be specifically designed for prophylaxis and/or for blocking malaria transmission to benefit both, the individual consumer and the community at large. Neem represents a good candidate for this purpose due to its inhibitory effects on the parasite stages that cause the clinical manifestations of malaria and on those responsible for infection in the vector. Furthermore, neem secondary metabolites have been shown to interfere with various physiological processes in insect vectors. This study was undertaken to assess the impact of the standardised neem extract NeemAzal on the fitness of the malaria vector Anopheles stephensi following repeated exposure to the product through consecutive blood meals on treated mice. METHODS: Batches of An. stephensi mosquitoes were offered 5 consecutive blood meals on female BALB/c mice treated with NeemAzal at an azadirachtin A concentration of 60, 105 or 150 mg/kg. The blood feeding capacity was estimated by measuring the haematin content of the rectal fluid excreted by the mosquitoes during feeding. The number of eggs laid was estimated by image analysis and their hatchability assessed by direct observations. RESULTS: A dose and frequency dependent impact of NeemAzal treatment on the mosquito feeding capacity, oviposition and egg hatchability was demonstrated. In the 150 mg/kg treatment group, the mosquito feeding capacity was reduced by 50% already at the second blood meal and by 50 to 80% in all treatment groups at the fifth blood meal. Consequently, a 50 - 65% reduction in the number of eggs laid per female mosquito was observed after the fifth blood meal in all treatment groups. Similarly, after the fifth treated blood meal exposure, hatchability was found to be reduced by 62% and 70% in the 105 and 150 mg/kg group resp

Journal article

Akinosoglou KA, Bushell ESC, Ukegbu CV, Schlegelmilch T, Cho J-S, Redmond S, Sala K, Christophides GK, Vlachou Det al., 2015, Characterization of Plasmodium developmental transcriptomes in Anopheles gambiae midgut reveals novel regulators of malaria transmission, CELLULAR MICROBIOLOGY, Vol: 17, Pages: 254-268, ISSN: 1462-5814

Journal article

Gendrin M, Rodgers FH, Yerbanga RS, Ouedraogo JB, Basanez M-G, Cohuet A, Christophides GKet al., 2015, Antibiotics in ingested human blood affect the mosquito microbiota and capacity to transmit malaria, NATURE COMMUNICATIONS, Vol: 6, ISSN: 2041-1723

Journal article

Upton LM, Povelones M, Christophides GK, 2015, Anopheles gambiae blood feeding Initiates an anticipatory defense response to plasmodium berghei, Journal of Innate Immunity, Vol: 7, Pages: 74-86, ISSN: 1662-8128

Mosquitoes have potent innate defense mechanisms that protect them from infection by diverse pathogens. Much remains unknown about how different pathogens are sensed and specific responses triggered. Leucine-Rich repeat IMmune proteins (LRIMs) are a mosquito-specific family of putative innate receptors. Although some LRIMs have been implicated in mosquito immune responses, the function of most family members is largely unknown. We screened Anopheles gambiae LRIMs by RNAi for effects on mosquito infection by rodent malaria and found that LRIM9 is a Plasmodium berghei antagonist with phenotypes distinct from family members LRIM1 and APL1C, which are key components of the mosquito complement-like pathway. LRIM9 transcript and protein levels are significantly increased after blood feeding but are unaffected by Plasmodium or midgut microbiota. Interestingly, LRIM9 in the hemolymph is strongly upregulated by direct injection of the ecdysteroid, 20-hydroxyecdysone. Our data suggest that LRIM9 may define a novel anti-Plasmodium immune defense mechanism triggered by blood feeding and that hormonal changes may alert the mosquito to bolster its defenses in anticipation of exposure to blood-borne pathogens.

Journal article

Neafsey DE, Waterhouse RM, Abai MR, Aganezov SS, Alekseyev MA, Allen JE, Amon J, Arca B, Arensburger P, Artemov G, Assour LA, Basseri H, Berlin A, Birren BW, Blandin SA, Brockman AI, Burkot TR, Burt A, Chan CS, Chauve C, Chiu JC, Christensen M, Costantini C, Davidson VLM, Deligianni E, Dottorini T, Dritsou V, Gabriel SB, Guelbeogo WM, Hall AB, Han MV, Hlaing T, Hughes DST, Jenkins AM, Jiang X, Jungreis I, Kakani EG, Kamali M, Kemppainen P, Kennedy RC, Kirmitzoglou IK, Koekemoer LL, Laban N, Langridge N, Lawniczak MKN, Lirakis M, Lobo NF, Lowy E, MacCallum RM, Mao C, Maslen G, Mbogo C, McCarthy J, Michel K, Mitchell SN, Moore W, Murphy KA, Naumenko AN, Nolan T, Novoa EM, O Loughlin S, Oringanje C, Oshaghi MA, Pakpour N, Papathanos PA, Peery AN, Povelones M, Prakash A, Price DP, Rajaraman A, Reimer LJ, Rinker DC, Rokas A, Russell TL, Sagnon NF, Sharakhova MV, Shea T, Simao FA, Simard F, Slotman MA, Somboon P, Stegniy V, Struchiner CJ, Thomas GWC, Tojo M, Topalis P, Tubio JMC, Unger MF, Vontas J, Walton C, Wilding CS, Willis JH, Wu Y-C, Yan G, Zdobnov EM, Zhou X, Catteruccia F, Christophides GK, Collins FH, Cornman RS, Crisanti A, Donnelly MJ, Emrich SJ, Fontaine MC, Gelbart W, Hahn MW, Hansen IA, Howell PI, Kafatos FC, Kellis M, Lawson D, Louis C, Luckhart S, Muskavitch MAT, Ribeiro JM, Riehle MA, Sharakhov IV, Tu Z, Zwiebel LJ, Besansky NJet al., 2015, Highly evolvable malaria vectors: The genomes of 16 Anopheles mosquitoes, Science, Vol: 347

Journal article

Giraldo-Calderon GI, Emrich SJ, MacCallum RM, Maslen G, Dialynas E, Topalis P, Ho N, Gesing S, Madey G, Collins FH, Lawson Det al., 2014, VectorBase: an updated bioinformatics resource for invertebrate vectors and other organisms related with human diseases, Nucleic Acids Research, Vol: 43, Pages: D707-D713, ISSN: 1362-4962

VectorBase is a National Institute of Allergy and Infectious Diseases supported Bioinformatics Resource Center (BRC) for invertebrate vectors of human pathogens. Now in its 11th year, VectorBase currently hosts the genomes of 35 organisms including a number of non-vectors for comparative analysis. Hosted data range from genome assemblies with annotated gene features, transcript and protein expression data to population genetics including variation and insecticide-resistance phenotypes. Here we describe improvements to our resource and the set of tools available for interrogating and accessing BRC data including the integration of Web Apollo to facilitate community annotation and providing Galaxy to support user-based workflows. VectorBase also actively supports our community through hands-on workshops and online tutorials. All information and data are freely available from our website at https://www.vectorbase.org/.

Journal article

Yassine H, Kamareddine L, Chamat S, Christophides GK, Osta MAet al., 2014, A Serine Protease Homolog Negatively Regulates TEP1 Consumption in Systemic Infections of the Malaria Vector Anopheles gambiae, JOURNAL OF INNATE IMMUNITY, Vol: 6, Pages: 806-818, ISSN: 1662-811X

Journal article

Talman AM, Prieto JH, Marques S, Ubaida-Mohien C, Lawniczak M, Wass MN, Xu T, Frank R, Ecker A, Stanway RS, Krishna S, Sternberg MJE, Christophides GK, Graham DR, Dinglasan RR, Yates JR, Sinden REet al., 2014, Proteomic analysis of the Plasmodium male gamete reveals the key role for glycolysis in flagellar motility, MALARIA JOURNAL, Vol: 13

Journal article

Yerbanga RS, Lucantoni L, Ouedraogo RK, Da DF, Yao FA, Yameogo KB, Churcher TS, Lupidi G, Taglialatela-Scafati O, Gouagna LC, Cohuet A, Christophides GK, Ouedraogo JB, Habluetzel Aet al., 2014, Transmission blocking activity of Azadirachta indica and Guiera senegalensis extracts on the sporogonic development of Plasmodium falciparum field isolates in Anopheles coluzzii mosquitoes, Parasites and Vectors, Vol: 7, Pages: 1-10, ISSN: 1756-3305

BackgroundTargeting the stages of the malaria parasites responsible for transmission from the human host to the mosquito vector is a key pharmacological strategy for malaria control. Research efforts to identify compounds that are active against these stages have significantly increased in recent years. However, at present, only two drugs are available, namely primaquine and artesunate, which reportedly act on late stage gametocytes.MethodsIn this study, we assessed the antiplasmodial effects of 5 extracts obtained from the neem tree Azadirachta indica and Guiera senegalensis against the early vector stages of Plasmodium falciparum, using field isolates. In an ex vivo assay gametocytaemic blood was supplemented with the plant extracts and offered to Anopheles coluzzii females by membrane feeding. Transmission blocking activity was evaluated by assessing oocyst prevalence and density on the mosquito midguts.ResultsInitial screening of the 5 plant extracts at 250 ppm revealed transmission blocking activity in two neem preparations. Up to a concentration of 70 ppm the commercial extract NeemAzal® completely blocked transmission and at 60 ppm mosquitoes of 4 out of 5 replicate groups remained uninfected. Mosquitoes fed on the ethyl acetate phase of neem leaves at 250 ppm showed a reduction in oocyst prevalence of 59.0% (CI95 12.0 - 79.0; p < 10-4) and in oocyst density of 90.5% (CI95 86.0 - 93.5; p < 10-4 ), while the ethanol extract from the same plant part did not exhibit any activity. No evidence of transmission blocking activity was found using G. senegalensis ethyl acetate extract from stem galls.ConclusionsThe results of this study highlight the potential of antimalarial plants for the discovery of novel transmission blocking molecules, and open up the potential of developing standardized transmission blocking herbal formulations as malaria control tools to complement currently used antimalarial drugs and combination treatment

Journal article

Stathopoulos S, Neafsey DE, Lawniczak MKN, Muskavitch MAT, Christophides GKet al., 2014, Genetic Dissection of Anopheles gambiae Gut Epithelial Responses to Serratia marcescens, PLOS PATHOGENS, Vol: 10, ISSN: 1553-7366

Journal article

Waldock J, Parham PE, Lelieveld J, Christophides GKet al., 2013, Climate and Human Health: The Impact of Climate Change on Vector-Borne Diseases, Paphos, Cyprus (17-19 October 2012), PATHOGENS AND GLOBAL HEALTH, Vol: 107, Pages: 387-392, ISSN: 2047-7724

Journal article

Povelones M, Upton L, Christophides G, 2013, EVIDENCE OF AN ANTI-PLASMODIUM ANTICIPATORY IMMUNE RESPONSE IN ANOPHELES GAMBIAE STIMULATED BY BLOOD FEEDING, Publisher: MANEY PUBLISHING, Pages: 401-401, ISSN: 2047-7724

Conference paper

Lawniczak M, Cohuet A, Christophides G, 2013, GENOME WIDE ASSOCIATION STUDIES IDENTIFYING LOCI UNDERLYING ANOPHELES GAMBIAE SUSCEPTIBILITY TO PLASMODIUM FALCIPARUM, PATHOGENS AND GLOBAL HEALTH, Vol: 107, Pages: 403-404, ISSN: 2047-7724

Journal article

Stathopoulos S, Christophides GK, 2013, GENETIC MAPPING OF ANOPHELES GAMBIAE GUT EPITHELIAL RESPONSES TO SERRATIA MARCESCENS, PATHOGENS AND GLOBAL HEALTH, Vol: 107, Pages: 422-423, ISSN: 2047-7724

Journal article

Gendrin M, Rodgers F, Cohuet A, Christophides Get al., 2013, IMPACT OF ANTIBIOTIC USE ON MOSQUITO MICROBIOTA AND ON MALARIA TRANSMISSION, PATHOGENS AND GLOBAL HEALTH, Vol: 107, Pages: 425-425, ISSN: 2047-7724

Journal article

Habtewold T, Christophides G, 2013, LEARNING HOW TO FIGHT MALARIA FROM NON-VECTOR MOSQUITOES, Publisher: MANEY PUBLISHING, Pages: 405-405, ISSN: 2047-7724

Conference paper

Midega J, Smith D, Olotu A, Mwangangi J, Nzovu J, Wambua J, Nyangweso G, Mbogo C, Christophides G, Bejon Pet al., 2013, WIND DIRECTION AND PROXIMITY TO LARVAL SITES DETERMINES MALARIA RISK IN KILIFI, KENYA, PATHOGENS AND GLOBAL HEALTH, Vol: 107, Pages: 446-447, ISSN: 2047-7724

Journal article

Midega J, Blight J, Lombardo F, Povelones M, Kafatos F, Christophides GKet al., 2013, Discovery and characterization of two Nimrod superfamily members in Anopheles gambiae, PATHOGENS AND GLOBAL HEALTH, Vol: 107, Pages: 463-474, ISSN: 2047-7724

Journal article

Povelones M, Christophides GK, 2013, Meeting report of the Mosquito Kolymbari Meeting 2013, PATHOGENS AND GLOBAL HEALTH, Vol: 107, Pages: 393-399, ISSN: 2047-7724

Journal article

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