Kafatos:George K. Christophides: Difference between revisions
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== [[Kafatos:Research|Research Interests]] == | == [[Kafatos:Research|Research Interests]] == | ||
Before my appointment by Imperial College London in June 2005, I was at the European Molecular Biology Laboratory (EMBL), in Heidelberg, Germany. There, I worked in the laboratory of Prof. Fotis C. Kafatos and I was centrally involved in genomic and post genomic research of the malaria mosquito Anopheles gambiae: sequencing of the A. gambiae genome and its comparative analysis with the genome of Drosophila melanogaster, specifically focusing on the comparative genomics of the innate immune system. I was also involved in the establishment of the DNA microarray technology at EMBL, and by using this technology I developed together with my colleague Dr George Dimopoulos the first DNA microarray for A. gambiae. This microarray was used as a pathfinder to explore the mosquito immune system and detect mechanisms of refractoriness to malaria infection. In December 2003, I was elected a Staff Scientist, the first level of the EMBL research faculty, by the EMBL Senior Scientist Committee. In this new role, and in affiliation with the laboratory of Prof Kafatos, I led a research team that focused on the development and exploitation of functional genomic tools towards better understanding of the immune system of A. gambiae and its role in malaria infection. | Before my appointment by Imperial College London in June 2005, I was at the European Molecular Biology Laboratory (EMBL), in Heidelberg, Germany. There, I worked in the laboratory of Prof. Fotis C. Kafatos and I was centrally involved in genomic and post genomic research of the malaria mosquito Anopheles gambiae: sequencing of the A. gambiae genome and its comparative analysis with the genome of Drosophila melanogaster, specifically focusing on the comparative genomics of the innate immune system. I was also involved in the establishment of the DNA microarray technology at EMBL, and by using this technology I developed together with my colleague Dr George Dimopoulos the first DNA microarray for A. gambiae. This microarray was used as a pathfinder to explore the mosquito immune system and detect mechanisms of refractoriness to malaria infection. In December 2003, I was elected a Staff Scientist, the first level of the EMBL research faculty, by the EMBL Senior Scientist Committee. In this new role, and in affiliation with the laboratory of Prof Kafatos, I led a research team that focused on the development and exploitation of functional genomic tools towards better understanding of the immune system of A. gambiae and its role in malaria infection.<br> | ||
The first functional genomic tool that we developed was a new EST microarray platform (MMC1) comprising 20,000 elements. At that time, MMC1 was the most advanced A. gambiae microarray platform encompassing approximately 9,000 unique genomic sequences. It was used by us and in collaboration with members of the Kafatos laboratory and external collaborators to study various aspects of the Anopheles biology, such as developmental and spatial gene expression, immune transcriptional networks, mosquito midgut responses to Plasmodium invasion, mosquito responses to viral infections and insecticide resistance. Since many MMC1 ESTs did not correspond to predicted genes in the A. gambiae genome, we provide functional bioinformatics annotation to these ESTs and show that at least 3,000 EST contigs likely correspond to currently non-predicted genes. One of the key discoveries deriving from our transcriptomic studies was LRIM1, a gene with no homologues in other organisms, which is robustly upregulated during bacterial and malaria infections. It turned out that LRIM1 protein is a very important Plasmodium parasite antagonist, implicated in killing and clearance of approximately 80% of Plasmodium berghei ookinetes during invasion of the mosquito midgut. It also targets for melanization the remaining 20% of the parasites; however, two other parasite agonists, CTL4 and CTLMA2, inhibit this reaction. This study attracted great attention and was one of the most influential in the mosquito immunity field. LRIM1 is also central in bacterial phagocytic pathways. | The first functional genomic tool that we developed was a new EST microarray platform (MMC1) comprising 20,000 elements. At that time, MMC1 was the most advanced A. gambiae microarray platform encompassing approximately 9,000 unique genomic sequences. It was used by us and in collaboration with members of the Kafatos laboratory and external collaborators to study various aspects of the Anopheles biology, such as developmental and spatial gene expression, immune transcriptional networks, mosquito midgut responses to Plasmodium invasion, mosquito responses to viral infections and insecticide resistance. Since many MMC1 ESTs did not correspond to predicted genes in the A. gambiae genome, we provide functional bioinformatics annotation to these ESTs and show that at least 3,000 EST contigs likely correspond to currently non-predicted genes. One of the key discoveries deriving from our transcriptomic studies was LRIM1, a gene with no homologues in other organisms, which is robustly upregulated during bacterial and malaria infections. It turned out that LRIM1 protein is a very important Plasmodium parasite antagonist, implicated in killing and clearance of approximately 80% of Plasmodium berghei ookinetes during invasion of the mosquito midgut. It also targets for melanization the remaining 20% of the parasites; however, two other parasite agonists, CTL4 and CTLMA2, inhibit this reaction. This study attracted great attention and was one of the most influential in the mosquito immunity field. LRIM1 is also central in bacterial phagocytic pathways.<br> | ||
Another area of focus of my group is the recognition of danger signals and signalling through NF-kappaB proteins in A. gambiae. We detected significant differences between mosquitoes and flies of the mechanisms of immune responses to bacterial infections. Both Gram-positive and negative bacteria are dealt with by the mosquito Imd pathway, which is also responsible for killing many parasites during a malaria infection. The pathway controls the expression of antimicrobial peptides and other immune related proteins, including LRIM1. Recent data show that signalling for bacterial and malaria infections are mediated by the pattern recognition receptor PGRPLC. | Another area of focus of my group is the recognition of danger signals and signalling through NF-kappaB proteins in A. gambiae. We detected significant differences between mosquitoes and flies of the mechanisms of immune responses to bacterial infections. Both Gram-positive and negative bacteria are dealt with by the mosquito Imd pathway, which is also responsible for killing many parasites during a malaria infection. The pathway controls the expression of antimicrobial peptides and other immune related proteins, including LRIM1. Recent data show that signalling for bacterial and malaria infections are mediated by the pattern recognition receptor PGRPLC.<br> | ||
Recently, we designed a new multifunctional genomic platform, MMC2, from approximately 13,000 amplicons corresponding to equal number of unique A. gambiae genes. MCC2 could be used to (a) construct an almost full mosquito transcriptome microarray, (b) to synthesize double stranded RNA (dsRNA) towards silencing of corresponding transcripts and (c) to produce protein tags to raise antibodies against all mosquito proteins. Microarrays of MMC2 amplicons are now used as a standard operational platform in various transcriptomic studies. Its use in conjunction with MMC1 comprising additional non-predicted genes represents one of the largest collections of unique A. gambiae sequences on chip. | Recently, we designed a new multifunctional genomic platform, MMC2, from approximately 13,000 amplicons corresponding to equal number of unique A. gambiae genes. MCC2 could be used to (a) construct an almost full mosquito transcriptome microarray, (b) to synthesize double stranded RNA (dsRNA) towards silencing of corresponding transcripts and (c) to produce protein tags to raise antibodies against all mosquito proteins. Microarrays of MMC2 amplicons are now used as a standard operational platform in various transcriptomic studies. Its use in conjunction with MMC1 comprising additional non-predicted genes represents one of the largest collections of unique A. gambiae sequences on chip.<br> | ||
== Education & Research == | == Education & Research == | ||
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Dr George K. Christophides Division of Cell & Molecular Biology g.christophides[at]imperial.ac.uk
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I am one of the PIs of the laboratory and a Senior Lecturer at Imperial College, London
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Imperial faculty webpage
Contact Details
Research Interests
Before my appointment by Imperial College London in June 2005, I was at the European Molecular Biology Laboratory (EMBL), in Heidelberg, Germany. There, I worked in the laboratory of Prof. Fotis C. Kafatos and I was centrally involved in genomic and post genomic research of the malaria mosquito Anopheles gambiae: sequencing of the A. gambiae genome and its comparative analysis with the genome of Drosophila melanogaster, specifically focusing on the comparative genomics of the innate immune system. I was also involved in the establishment of the DNA microarray technology at EMBL, and by using this technology I developed together with my colleague Dr George Dimopoulos the first DNA microarray for A. gambiae. This microarray was used as a pathfinder to explore the mosquito immune system and detect mechanisms of refractoriness to malaria infection. In December 2003, I was elected a Staff Scientist, the first level of the EMBL research faculty, by the EMBL Senior Scientist Committee. In this new role, and in affiliation with the laboratory of Prof Kafatos, I led a research team that focused on the development and exploitation of functional genomic tools towards better understanding of the immune system of A. gambiae and its role in malaria infection.
The first functional genomic tool that we developed was a new EST microarray platform (MMC1) comprising 20,000 elements. At that time, MMC1 was the most advanced A. gambiae microarray platform encompassing approximately 9,000 unique genomic sequences. It was used by us and in collaboration with members of the Kafatos laboratory and external collaborators to study various aspects of the Anopheles biology, such as developmental and spatial gene expression, immune transcriptional networks, mosquito midgut responses to Plasmodium invasion, mosquito responses to viral infections and insecticide resistance. Since many MMC1 ESTs did not correspond to predicted genes in the A. gambiae genome, we provide functional bioinformatics annotation to these ESTs and show that at least 3,000 EST contigs likely correspond to currently non-predicted genes. One of the key discoveries deriving from our transcriptomic studies was LRIM1, a gene with no homologues in other organisms, which is robustly upregulated during bacterial and malaria infections. It turned out that LRIM1 protein is a very important Plasmodium parasite antagonist, implicated in killing and clearance of approximately 80% of Plasmodium berghei ookinetes during invasion of the mosquito midgut. It also targets for melanization the remaining 20% of the parasites; however, two other parasite agonists, CTL4 and CTLMA2, inhibit this reaction. This study attracted great attention and was one of the most influential in the mosquito immunity field. LRIM1 is also central in bacterial phagocytic pathways.
Another area of focus of my group is the recognition of danger signals and signalling through NF-kappaB proteins in A. gambiae. We detected significant differences between mosquitoes and flies of the mechanisms of immune responses to bacterial infections. Both Gram-positive and negative bacteria are dealt with by the mosquito Imd pathway, which is also responsible for killing many parasites during a malaria infection. The pathway controls the expression of antimicrobial peptides and other immune related proteins, including LRIM1. Recent data show that signalling for bacterial and malaria infections are mediated by the pattern recognition receptor PGRPLC.
Recently, we designed a new multifunctional genomic platform, MMC2, from approximately 13,000 amplicons corresponding to equal number of unique A. gambiae genes. MCC2 could be used to (a) construct an almost full mosquito transcriptome microarray, (b) to synthesize double stranded RNA (dsRNA) towards silencing of corresponding transcripts and (c) to produce protein tags to raise antibodies against all mosquito proteins. Microarrays of MMC2 amplicons are now used as a standard operational platform in various transcriptomic studies. Its use in conjunction with MMC1 comprising additional non-predicted genes represents one of the largest collections of unique A. gambiae sequences on chip.
Education & Research
Diploma in Biology, 1994, University of Athens, Greece
PhD in Molecular Biology, 2000, University of Athens, Greece
Research Assistant, 1994-1995, University of Athens, Greece
Research Assistant, 1996-1999, University of Athens, Greece
Marie-Curie Postdoctoral fellow, 2000-2002, European Molecular Biology Laboratory, Heidelberg, Germany
Research Associate, 2003-2004, European Molecular Biology Laboratory, Heidelberg, Germany
Staff Scientist, 2004-2005, European Molecular Biology Laboratory, Heidelberg, Germany
Senior Lecturer, 2005-present, Division of Cell& Molecular Biology, Imperial College London, London, Untited Kingdom
Publications
- Vontas J, Blass C, Koutsos AC, David JP, Kafatos FC, Louis C, Hemingway J, Christophides GK, and Ranson H. Gene expression in insecticide resistant and susceptible Anopheles gambiae strains constitutively or after insecticide exposure. Insect Mol Biol. 2005 Oct;14(5):509-21. DOI:10.1111/j.1365-2583.2005.00582.x |
- Sim C, Hong YS, Vanlandingham DL, Harker BW, Christophides GK, Kafatos FC, Higgs S, and Collins FH. Modulation of Anopheles gambiae gene expression in response to o'nyong-nyong virus infection. Insect Mol Biol. 2005 Oct;14(5):475-81. DOI:10.1111/j.1365-2583.2005.00578.x |
- Meister S, Kanzok SM, Zheng XL, Luna C, Li TR, Hoa NT, Clayton JR, White KP, Kafatos FC, Christophides GK, and Zheng L. Immune signaling pathways regulating bacterial and malaria parasite infection of the mosquito Anopheles gambiae. Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11420-5. DOI:10.1073/pnas.0504950102 |
- Vlachou D, Schlegelmilch T, Christophides GK, and Kafatos FC. Functional genomic analysis of midgut epithelial responses in Anopheles during Plasmodium invasion. Curr Biol. 2005 Jul 12;15(13):1185-95. DOI:10.1016/j.cub.2005.06.044 |
- Belyakin SN, Christophides GK, Alekseyenko AA, Kriventseva EV, Belyaeva ES, Nanayev RA, Makunin IV, Kafatos FC, and Zhimulev IF. Genomic analysis of Drosophila chromosome underreplication reveals a link between replication control and transcriptional territories. Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8269-74. DOI:10.1073/pnas.0502702102 |
- Kriventseva EV, Koutsos AC, Blass C, Kafatos FC, Christophides GK, and Zdobnov EM. AnoEST: toward A. gambiae functional genomics. Genome Res. 2005 Jun;15(6):893-9. DOI:10.1101/gr.3756405 |
- Christophides GK. Transgenic mosquitoes and malaria transmission. Cell Microbiol. 2005 Mar;7(3):325-33. DOI:10.1111/j.1462-5822.2005.00495.x |
- Hall N, Karras M, Raine JD, Carlton JM, Kooij TW, Berriman M, Florens L, Janssen CS, Pain A, Christophides GK, James K, Rutherford K, Harris B, Harris D, Churcher C, Quail MA, Ormond D, Doggett J, Trueman HE, Mendoza J, Bidwell SL, Rajandream MA, Carucci DJ, Yates JR 3rd, Kafatos FC, Janse CJ, Barrell B, Turner CM, Waters AP, and Sinden RE. A comprehensive survey of the Plasmodium life cycle by genomic, transcriptomic, and proteomic analyses. Science. 2005 Jan 7;307(5706):82-6. DOI:10.1126/science.1103717 |
- Meister S, Koutsos AC, and Christophides GK. The Plasmodium parasite--a 'new' challenge for insect innate immunity. Int J Parasitol. 2004 Dec;34(13-14):1473-82. DOI:10.1016/j.ijpara.2004.10.004 |
- Osta MA, Christophides GK, Vlachou D, and Kafatos FC. Innate immunity in the malaria vector Anopheles gambiae: comparative and functional genomics. J Exp Biol. 2004 Jul;207(Pt 15):2551-63. DOI:10.1242/jeb.01066 |
- Christophides GK, Vlachou D, and Kafatos FC. Comparative and functional genomics of the innate immune system in the malaria vector Anopheles gambiae. Immunol Rev. 2004 Apr;198:127-48. DOI:10.1111/j.0105-2896.2004.0127.x |
- Osta MA, Christophides GK, and Kafatos FC. Effects of mosquito genes on Plasmodium development. Science. 2004 Mar 26;303(5666):2030-2. DOI:10.1126/science.1091789 |
- Komitopoulou K, Christophides GK, Kalosaka K, Chrysanthis G, Theodoraki MA, Savakis C, Zacharopoulou A, and Mintzas AC. Medfly promoters relevant to the sterile insect technique. Insect Biochem Mol Biol. 2004 Feb;34(2):149-57. DOI:10.1016/j.ibmb.2003.06.016 |
- Kumar S, Christophides GK, Cantera R, Charles B, Han YS, Meister S, Dimopoulos G, Kafatos FC, and Barillas-Mury C. The role of reactive oxygen species on Plasmodium melanotic encapsulation in Anopheles gambiae. Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14139-44. DOI:10.1073/pnas.2036262100 |
- Christophides GK, Zdobnov E, Barillas-Mury C, Birney E, Blandin S, Blass C, Brey PT, Collins FH, Danielli A, Dimopoulos G, Hetru C, Hoa NT, Hoffmann JA, Kanzok SM, Letunic I, Levashina EA, Loukeris TG, Lycett G, Meister S, Michel K, Moita LF, Müller HM, Osta MA, Paskewitz SM, Reichhart JM, Rzhetsky A, Troxler L, Vernick KD, Vlachou D, Volz J, von Mering C, Xu J, Zheng L, Bork P, and Kafatos FC. Immunity-related genes and gene families in Anopheles gambiae. Science. 2002 Oct 4;298(5591):159-65. DOI:10.1126/science.1077136 |
- Zdobnov EM, von Mering C, Letunic I, Torrents D, Suyama M, Copley RR, Christophides GK, Thomasova D, Holt RA, Subramanian GM, Mueller HM, Dimopoulos G, Law JH, Wells MA, Birney E, Charlab R, Halpern AL, Kokoza E, Kraft CL, Lai Z, Lewis S, Louis C, Barillas-Mury C, Nusskern D, Rubin GM, Salzberg SL, Sutton GG, Topalis P, Wides R, Wincker P, Yandell M, Collins FH, Ribeiro J, Gelbart WM, Kafatos FC, and Bork P. Comparative genome and proteome analysis of Anopheles gambiae and Drosophila melanogaster. Science. 2002 Oct 4;298(5591):149-59. DOI:10.1126/science.1077061 |
- Holt RA, Subramanian GM, Halpern A, Sutton GG, Charlab R, Nusskern DR, Wincker P, Clark AG, Ribeiro JM, Wides R, Salzberg SL, Loftus B, Yandell M, Majoros WH, Rusch DB, Lai Z, Kraft CL, Abril JF, Anthouard V, Arensburger P, Atkinson PW, Baden H, de Berardinis V, Baldwin D, Benes V, Biedler J, Blass C, Bolanos R, Boscus D, Barnstead M, Cai S, Center A, Chaturverdi K, Christophides GK, Chrystal MA, Clamp M, Cravchik A, Curwen V, Dana A, Delcher A, Dew I, Evans CA, Flanigan M, Grundschober-Freimoser A, Friedli L, Gu Z, Guan P, Guigo R, Hillenmeyer ME, Hladun SL, Hogan JR, Hong YS, Hoover J, Jaillon O, Ke Z, Kodira C, Kokoza E, Koutsos A, Letunic I, Levitsky A, Liang Y, Lin JJ, Lobo NF, Lopez JR, Malek JA, McIntosh TC, Meister S, Miller J, Mobarry C, Mongin E, Murphy SD, O'Brochta DA, Pfannkoch C, Qi R, Regier MA, Remington K, Shao H, Sharakhova MV, Sitter CD, Shetty J, Smith TJ, Strong R, Sun J, Thomasova D, Ton LQ, Topalis P, Tu Z, Unger MF, Walenz B, Wang A, Wang J, Wang M, Wang X, Woodford KJ, Wortman JR, Wu M, Yao A, Zdobnov EM, Zhang H, Zhao Q, Zhao S, Zhu SC, Zhimulev I, Coluzzi M, della Torre A, Roth CW, Louis C, Kalush F, Mural RJ, Myers EW, Adams MD, Smith HO, Broder S, Gardner MJ, Fraser CM, Birney E, Bork P, Brey PT, Venter JC, Weissenbach J, Kafatos FC, Collins FH, and Hoffman SL. The genome sequence of the malaria mosquito Anopheles gambiae. Science. 2002 Oct 4;298(5591):129-49. DOI:10.1126/science.1076181 |
- Dimopoulos G, Christophides GK, Meister S, Schultz J, White KP, Barillas-Mury C, and Kafatos FC. Genome expression analysis of Anopheles gambiae: responses to injury, bacterial challenge, and malaria infection. Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8814-9. DOI:10.1073/pnas.092274999 |
- Christophides GK, Savakis C, Mintzas AC, and Komitopoulou K. Expression and function of the Drosophila melanogaster ADH in male Ceratitis capitata adults: a potential strategy for medfly genetic sexing based on gene-transfer technology. Insect Mol Biol. 2001 Jun;10(3):249-54. DOI:10.1046/j.1365-2583.2001.00265.x |
- Christophides GK, Livadaras I, Savakis C, and Komitopoulou K. Two medfly promoters that have originated by recent gene duplication drive distinct sex, tissue and temporal expression patterns. Genetics. 2000 Sep;156(1):173-82. DOI:10.1093/genetics/156.1.173 |
- Christophides GK, Mintzas AC, and Komitopoulou K. Organization, evolution and expression of a multigene family encoding putative members of the odourant binding protein family in the medfly Ceratitis capitata. Insect Mol Biol. 2000 Apr;9(2):185-95. DOI:10.1046/j.1365-2583.2000.00176.x |
