Molecular Aspects of Tsetse and Trypanosome Transmission

Summary

Principal Investigator: S Aksoy
Affiliation: Yale University
Country: USA
Abstract: African trypanosomiasis is once again a major public health problem throughout much of Africa. Control strategies are limited due to the lack of mammalian vaccines and efficacious and affordable drugs. The recent developments in recombinant DNA technologies stand to improve existing vector control measures, but progress in this are has been hampered by the lack of information on the molecular aspects of tsetse and its interactions with trypanosomes. Tsetse flies are in general refractory to the transmission of African trypanosomes although the molecular basis for refractoriness is unknown. Pdor induction of the tsetse immune system can reduce parasite transmission indicating that tsetse's innate defense surveillance system is capable of terminating the development of trypanosomes. In the work proposed here, a comprehensive panel of immune-responsive genes will be identified using several different molecular strategies and their expression profiles in response to different immune challenges will be analyzed. Both systemic and local responses, respectively mediated by fat body and proventriculus tissue, will be investigated at the molecular level. Functional studies are proposed with several key antimicrobial gene products to understand their role in parasite transmission. This study will allow us to begin to understand the components of the tsetse immune system and the interactions they exhibit with trypanosomes during the parasite establishment and transmission in the fly. Although germ line transformation approach is difficult in tsetse because of its unusual reproductive biology, expression of transgenes in the gut symbionts of tsetse, particularly Sodalis glossinidius, may prove a valuable strategy to control disease transmission. Central to such a strategy will be identification of suitable genes for use as transgenes. Immunity genes are strong =candidates which this study may help to identify. These genes may also play a role in differentiation of trypanosomes and again, this project will identify potential candidates.
Funding Period: 2002-12-15 - 2008-11-30
more information: NIH RePORT

Top Publications

  1. ncbi An antimicrobial peptide with trypanocidal activity characterized from Glossina morsitans morsitans
    Youjia Hu
    Department of Epidemiology and Public Health, Section of Vector Biology, Yale University, School of Medicine, 60 College St, 606 LEPH, New Haven, CT 06510, USA
    Insect Biochem Mol Biol 35:105-15. 2005
  2. pmc The obligate mutualist Wigglesworthia glossinidia influences reproduction, digestion, and immunity processes of its host, the tsetse fly
    Roshan Pais
    Yale School of Public Heath, Department of Epidemiology of Microbial Diseases, New Haven, CT 06520, USA
    Appl Environ Microbiol 74:5965-74. 2008
  3. pmc Analysis of milk gland structure and function in Glossina morsitans: milk protein production, symbiont populations and fecundity
    Geoffrey M Attardo
    Yale School of Public Health, Department of Epidemiology and Microbial Diseases, 60 College Street, 606 LEPH New Haven, CT 06510, USA
    J Insect Physiol 54:1236-42. 2008
  4. pmc Characterization of the antimicrobial peptide attacin loci from Glossina morsitans
    J Wang
    Yale University School of Medicine, Department of Epidemiology and Public Health, 60 College Street, New Haven, CT 06510, USA
    Insect Mol Biol 17:293-302. 2008
  5. pmc Infections with immunogenic trypanosomes reduce tsetse reproductive fitness: potential impact of different parasite strains on vector population structure
    Changyun Hu
    Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut, USA
    PLoS Negl Trop Dis 2:e192. 2008
  6. ncbi Refractoriness in tsetse flies (Diptera: Glossinidae) may be a matter of timing
    Dana Nayduch
    Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06510, USA
    J Med Entomol 44:660-5. 2007
  7. pmc Molecular aspects of transferrin expression in the tsetse fly (Glossina morsitans morsitans)
    Nurper Guz
    Department of Epidemiology and Public Health, Yale University School of Medicine, 60 College Street, 606 LEPH, New Haven, CT 06510, USA
    J Insect Physiol 53:715-23. 2007
  8. pmc Molecular characterization of iron binding proteins from Glossina morsitans morsitans (Diptera: Glossinidae)
    Patricia M Strickler-Dinglasan
    Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06510, USA
    Insect Biochem Mol Biol 36:921-33. 2006
  9. pmc Molecular aspects of viviparous reproductive biology of the tsetse fly (Glossina morsitans morsitans): regulation of yolk and milk gland protein synthesis
    Geoffrey M Attardo
    Department of Epidemiology and Public Health, Yale University School of Medicine, 606 LEPH New Haven, CT 06510, USA
    J Insect Physiol 52:1128-36. 2006
  10. pmc Interspecific transfer of bacterial endosymbionts between tsetse fly species: infection establishment and effect on host fitness
    Brian L Weiss
    Department of Epidemiology and Public Health, Yale University School of Medicine, LEPH 606, 60 College Street, New Haven, CT 06510, USA
    Appl Environ Microbiol 72:7013-21. 2006

Scientific Experts

  • S Aksoy
  • Dana Nayduch
  • Geoffrey M Attardo
  • Nurper Guz
  • Brian L Weiss
  • Changyun Hu
  • Yineng Wu
  • Claudia Lohs
  • J Wang
  • Roshan Pais
  • Rita V M Rio
  • Abdelaziz Heddi
  • G M Attardo
  • Patricia M Strickler-Dinglasan
  • Youjia Hu
  • Suleyman Yildirim
  • M Hattori
  • Uzma H Alam
  • Alison P Galvani
  • Terry W Pearson
  • A Toyoda
  • Jonathon J Schwank
  • Lee R Haines
  • C Amemiya
  • C Hu
  • Amy F Savage
  • Nicholas S Tolwinski
  • Y Wu
  • M Berriman
  • A Stuart
  • Jan Medlock
  • Jingwen Wang
  • Rosa Mouchotte
  • E Caler
  • S A H Perkin
  • Yi Neng Wu
  • Zheyang Wu
  • P Strickler-Dinglasan
  • Geoffrey Attardo
  • M B Soares
  • N El-Sayeed
  • M F Bonaldo
  • Patricia Strickler-Dinglasan

Detail Information

Publications14

  1. ncbi An antimicrobial peptide with trypanocidal activity characterized from Glossina morsitans morsitans
    Youjia Hu
    Department of Epidemiology and Public Health, Section of Vector Biology, Yale University, School of Medicine, 60 College St, 606 LEPH, New Haven, CT 06510, USA
    Insect Biochem Mol Biol 35:105-15. 2005
    ..We discuss a paratransgenic strategy, which involves the expression of trypanocidal molecules such as recGmAttA1 in the midgut symbiont Sodalis in vivo to reduce trypanosome transmission...
  2. pmc The obligate mutualist Wigglesworthia glossinidia influences reproduction, digestion, and immunity processes of its host, the tsetse fly
    Roshan Pais
    Yale School of Public Heath, Department of Epidemiology of Microbial Diseases, New Haven, CT 06520, USA
    Appl Environ Microbiol 74:5965-74. 2008
    ..The ability to rear adult tsetse that lack the obligate Wigglesworthia endosymbionts will now enable functional investigations into this ancient symbiosis...
  3. pmc Analysis of milk gland structure and function in Glossina morsitans: milk protein production, symbiont populations and fecundity
    Geoffrey M Attardo
    Yale School of Public Health, Department of Epidemiology and Microbial Diseases, 60 College Street, 606 LEPH New Haven, CT 06510, USA
    J Insect Physiol 54:1236-42. 2008
    ..We discuss the significance of the milk gland in larval nutrition and in transmission of symbiotic bacteria to developing offspring...
  4. pmc Characterization of the antimicrobial peptide attacin loci from Glossina morsitans
    J Wang
    Yale University School of Medicine, Department of Epidemiology and Public Health, 60 College Street, New Haven, CT 06510, USA
    Insect Mol Biol 17:293-302. 2008
    ..Transcription of AttD is significantly less relative to the other two genes, and is preferentially induced in the fat body of parasitized flies. These results indicate that the different attacin genes may be differentially regulated...
  5. pmc Infections with immunogenic trypanosomes reduce tsetse reproductive fitness: potential impact of different parasite strains on vector population structure
    Changyun Hu
    Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut, USA
    PLoS Negl Trop Dis 2:e192. 2008
    ..Potential repercussions for vector population growth, parasite-host coevolution, and disease prevalence are discussed...
  6. ncbi Refractoriness in tsetse flies (Diptera: Glossinidae) may be a matter of timing
    Dana Nayduch
    Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06510, USA
    J Med Entomol 44:660-5. 2007
    ..pallidipes. The role of early, uninduced attacin expression, and its role in relative refractoriness in tsetse, is discussed...
  7. pmc Molecular aspects of transferrin expression in the tsetse fly (Glossina morsitans morsitans)
    Nurper Guz
    Department of Epidemiology and Public Health, Yale University School of Medicine, 60 College Street, 606 LEPH, New Haven, CT 06510, USA
    J Insect Physiol 53:715-23. 2007
    ..Analysis of tsetse that have cured the parasite challenge shows normal levels of GmmTsf. This observation suggests that the parasite in competing for the availability of limited dietary iron may manipulate host gene expression...
  8. pmc Molecular characterization of iron binding proteins from Glossina morsitans morsitans (Diptera: Glossinidae)
    Patricia M Strickler-Dinglasan
    Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06510, USA
    Insect Biochem Mol Biol 36:921-33. 2006
    ..On the other hand, GmmFer1HCH maintains both the conserved ferroxidase center and the 5'UTR IRE; however, transcript variants suggest a more extensive regulatory mechanism for this subunit...
  9. pmc Molecular aspects of viviparous reproductive biology of the tsetse fly (Glossina morsitans morsitans): regulation of yolk and milk gland protein synthesis
    Geoffrey M Attardo
    Department of Epidemiology and Public Health, Yale University School of Medicine, 606 LEPH New Haven, CT 06510, USA
    J Insect Physiol 52:1128-36. 2006
    ..These results demonstrate that both GmmYP1 and GmmMGP are involved in tsetse reproductive biology, the former associated with the process of oogenesis and the latter with larvigenesis...
  10. pmc Interspecific transfer of bacterial endosymbionts between tsetse fly species: infection establishment and effect on host fitness
    Brian L Weiss
    Department of Epidemiology and Public Health, Yale University School of Medicine, LEPH 606, 60 College Street, New Haven, CT 06510, USA
    Appl Environ Microbiol 72:7013-21. 2006
    ..Our ability to transinfect tsetse flies is indicative of Sodalis ' recent evolutionary history with its tsetse fly host and demonstrates that this procedure may be used as a means of streamlining future paratransgenesis experiments...
  11. ncbi Analysis of fat body transcriptome from the adult tsetse fly, Glossina morsitans morsitans
    G M Attardo
    Department of Epidemiology and Public Health, Section of Vector Biology, Yale University School of Medicine, New Haven, CT 06510, USA
    Insect Mol Biol 15:411-24. 2006
    ..Milk gland protein, apparently important for larval nutrition, however, is primarily synthesized by accessory milk gland tissue...
  12. ncbi Innate immune responses regulate trypanosome parasite infection of the tsetse fly Glossina morsitans morsitans
    Changyun Hu
    Department of Epidemiology and Public Health, Yale University School of Medicine, 60 College St, 606 LEPH, New Haven, CT 06510, USA
    Mol Microbiol 60:1194-204. 2006
    ..Our results provide the first direct evidence for the involvement of antimicrobial peptides in trypanosome transmission in tsetse...
  13. ncbi Interactions among multiple genomes: tsetse, its symbionts and trypanosomes
    Serap Aksoy
    Department of Epidemiology and Public Health, Yale University School of Medicine, 60 College St, 606 LEPH, New Haven, CT 06510, USA
    Insect Biochem Mol Biol 35:691-8. 2005
    ....
  14. pmc An insect symbiosis is influenced by bacterium-specific polymorphisms in outer-membrane protein A
    Brian L Weiss
    Department of Epidemiology and Public Health, Section of Vector Biology, Yale University School of Medicine, LEPH 606, 60 College Street, New Haven, CT 06520, USA
    Proc Natl Acad Sci U S A 105:15088-93. 2008
    ..coli K12. Our results show that polymorphisms in the exposed loop domains of OmpA represent a microbial adaptation that mediates host tolerance of endogenous symbiotic bacteria...